Due to the proven clinical benefit of cascade testing, further research on obstacles to systematic implementation and uptake of testing for relatives of any proband with a medically actionable variant is warranted.Ĭascade testing is the process of providing genetic counseling and testing to at-risk blood relatives following the detection of a pathogenic variant in a disease-causing gene in a family member (i.e., the proband). Consistently higher rates of cascade testing among families of diagnostic probands may be due to a perceived urgency because of personal or family history of disease. A positive result in an FH gene was returned to 1,647 diagnostic probands (25.3%) and 67 proactive probands (0.62%), leading to cascade testing among families of 360 diagnostic probands (21.9%) and 4 proactive probands (6.0%) ( p < 0.01). Cascade testing due to a positive result in an HCS gene was more commonly pursued when the diagnostic proband was White, had a finding in a gene associated with a CDC Tier 1 condition, or had a personal history of cancer, or when the proactive proband was female. A positive result in an HCS gene was returned to 23,272 diagnostic probands (9.4%) and 970 proactive probands (6.1%), leading to cascade testing among families of 6,611 diagnostic probands (28.4%) and 89 proactive probands (9.2%) ( p < 0.0001). A positive result in a gene associated with a CDC Tier 1 condition was identified in 10,520 diagnostic probands (4.1%) and 337 proactive probands (2.1%), leading to cascade testing among families of 3,305 diagnostic probands (31.4%) and 36 proactive probands (10.7%) ( p < 0.0001). A total of 270,715 probands were eligible for inclusion in the study (diagnostic n = 254,281,93.9% proactive n = 16,434, 6.1%). Among probands with a positive finding, cascade testing rates and influencing factors were assessed. The proportion of probands with a medically actionable (positive) finding were calculated based on genes associated with Centers for Disease Control and Prevention (CDC) Tier 1 conditions, HCS genes, and FH genes. We performed a retrospective, cross-sectional study comparing cascade genetic testing rates among relatives of probands who received either diagnostic germline testing or non-indication-based proactive screening via next-generation sequencing (NGS)-based multigene panels for hereditary cancer syndromes (HCS) and/or familial hypercholesterolemia (FH). Invitae, San Francisco, CA, United StatesĪlthough multiple factors can influence the uptake of cascade genetic testing, the impact of proband indication has not been studied.
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Real-time statusĪlways know where your agreement is in the signing process. DocuSign offers robust form functionality including checkboxes, radio buttons, dropdown tags, and text, numeric and currency fields. Flatten the fields, converting the contents of the fields from the original PDF form into a permanent, read-only part of your document.Īdd standard fields to your agreement like a signature or date, or create and save custom fields.Delete all of the fields and any data they contain.Any data that was entered into the original form is included in the DocuSign field. Assign all of the fields to a recipient.You choose how to apply the converted fields as you set up your document: When you upload a PDF, DocuSign automatically recognizes and converts the PDF fields to signer fields. Sending and signing is fast, easy and intuitive. Send documents with DocuSign and have your customers sign and send back your document within a matter of minutes. Prepare PDFs for electronic signature quickly You can choose if you want to select a preformatted signature style or if you will draw your signature.If you would like to change your name or initials, type the changes in the Full Name and Initials fields. Verify your name and initials are correct.The first time you click a SIGN or INITIAL field, you will be asked to adopt a signature and initials.Add the email address for where you want to send the signed document.Click to agree to use electronic signature for this document. Quickly upload an Adobe PDF document and add an electronic signature to the signature field using DocuSign eSignature: How to add an electronic signature to an Adobe PDF Most insurance policies have endorsements now providing for identity theft. However, though the internet can be a place of vulnerability, one can and should take precautions to be armed against the many cyber pirates of our world today. Although there are modern day “pirates” roaming the open seas, it seems that there is an vast realm of internet oceans that new breeds of pirates are trolling. Those seas are an unknown and unfamiliar world to most people, but it’s fast becoming a place that many must live on to survive. It requires an understanding of potential information threats, such as viruses and other malicious code according to Techopedia. From an insurance perspective, the peril (pirate) in this story above is “identity theft”.Ĭybersecurity, a word that has become well known in the past few years, refers to preventative methods used to protect information from being stolen, compromised or attacked. In an earlier post,, I wrote how the word pirate etymology is closely tied to the word “peril”. Yet, it highlights an looming area of concern in today’s world. The above story originated solely from a fertile imagination and yes, it's mine. Taking a deep breath, as the pirate edged nearer to the radar line, Jacobi prepared to sound the alarm. He could only hope for few casualties in what could be a fearsome battle. Once Captain Hendricks hit the inner code of the fake Fort of Cyber Gold, he would signal and for once, the feared pirate would be on the defensive rather than the offense. Jacobi’s team waited behind him for the order. His ship cut across the screen in record time. Jacobi watched the screen as he noted Captain Hendricks pausing for a brief moment before resuming his course. He had hopes the heist he was now preparing to hack was the mother lode of all time. Turning back to the screen, he stared intently at the communications line he now traveled. Something that would hail him as the most terrifying pirate of Cyber world of all time. Staring at the names and information, he realized that the medium-sized business ship that they had just raided in the realm they lived in, didn’t hit that satisfaction core deep within his cold heart anymore. We left our mark.” Captain smiled slightly as he took the reports. They didn’t have any firewalls, or cybersecurity systems in place. “We have ‘em all, Captain the place had no chance at stopping us. “Names, social security numbers, passwords, and medical reports” Briton said, his deep voice somewhat menacing. Musing on his ill-gotten wealth and the power it held, Hendricks was interrupted by Briton, his quartermaster, as he stepped into the cabin, handing him the latest conquering reports. He thought of all the storerooms deep within the bowels of his ship that held trunks of his golden treasure. He was hungry for bigger fish, better treasure than what he had hacked so far. Suddenly, he stood and walked over to the portal window, to stare out at the dark skies. Behind him, box after box, crate after crate, treasures overflowed. He, too, stared at a computer screen, but his intent was much different than the Quasi Guards. He was Captain Hendricks, a pirate of a world that many had never accessed nor dreamed existed. Jacobi couldn’t help but smile as he watched the pirate ship move.Īcross the oceans blue, in a small cabin room on the ship, sat a small stature of a man wearing an odd mechanical-looking headset. A fake Fort of Gold designed to catch a pirate. The notorious captain of the cyber pirates hadn’t yet discovered that he was being tracked, as he moved along one of the communications fiber lines that Jacobi and his team had set up this particular communication line was a setup… a ruse. Jacobi could feel the rising excitement in the pit of his stomach that always flowed through his veins when Captain Hendricks was spotted, but this time it was different. Straightening, he refocused on the black screen dotted with a myriad of lines and moving red flashing lights. Being in the Quasi Guard Captain’s role was not turning out to be what he expected long hours and little recognition.He leaned back and massaged the back of his neck. Jacobi squinted at the computer screen that he had been sitting in front of for days. If you add the number, format it like this: 978-X-XXXX-XXXX-X. If you do add it, make sure it matches the number assigned to your book. You can add an International Standard Book Number (ISBN) to your copyright page if you want, but it’s not required. If you copy content from another document and paste it into the template, the formatting may transfer and require correction. Visit Set Trim Size, Bleed, and Margins for more information. If your manuscript contains images or graphics that bleed to the edge of the page, you’ll need to increase the trim size. If your book contains bleed or is written in Japanese, please convert your file to a PDF before uploading to KDP.Only blank templates are available for Japanese.If there is remaining template text in your manuscript, you may receive an error on upload, or your manuscript may be rejected on review. Important: Make sure to remove any template sample text from your final manuscript. To find your template, click Download and open the ZIP folder. If you're unsure which size to pick, find books with content similar to yours to get an idea of what readers expect. The most common trim size for paperbacks in the US is 6" x 9" (15.24 x 22.86 cm), but you have several trim size options. Customize the parts you want to keep, and delete the sections you don't. The templates with sample content include formatted front matter (e.g., title page, table of contents) and chapters with placeholder text. The blank templates have the page size and margins set. 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Can I offer discounts to books in my series?.How to create a series with multiple authors.Where can I find my Amazon Series Page?.Kindle Vella - Royalties, Reporting, and Payments.International Standard Book Number (ISBN).Make Your Book More Discoverable with Keywords.Previewing and Publishing Your Kindle Create Book.Prepare Print Replica Books with Kindle Create.Prepare Comic eBooks with Kindle Create.Prepare Reflowable and Print Books with Kindle Create.Publishing Service Providers & Resources.What file formats are supported for eBook manuscripts?.Why is my cover image not updating on Amazon?.What criteria does my eBook's cover image need to meet?.Fix Paperback and Hardcover Formatting Issues.Paperback and Hardcover Manuscript Templates.Format Front Matter, Body Matter, and Back Matter.How EU Prices Affect List Price Requirements.EIN for Corporations and Non-Individual Entities But even the most thick-skinned kids may be shell-shocked by the film's conclusion. Writer Justin Monjo has a cinematic fix for that, explaining that the tragedy wasn't in vain and allowing the teen girl in the modern story to succeed. The boy's hard work and protective measures don't pay off, in the cruelest of ways. But the cheer comes to a devastating conclusion, and that defies the direction of most of today's family movies. Kids almost always respond to seeing others their age playing with wild animals it's a fantasy come true. Percival, are adorable, and a memorable game of hide-and-seek is downright precious. On the other hand, who knew pelicans could make such good friends? The antics featuring young Michael's (Finn Little) pet, Mr. From there, the story moseys along at a pace that might bore some kids. This adaptation brings those elements to life, but it wraps the child's story into an adult one - and, in doing so, it's likely to lose younger audiences within the first 10 minutes. Australian children are taught Storm Boy (the book) in elementary school: The story is full of exploration and adventure, love, loss, unexpected friendship, finding your voice, appreciating other cultures, and understanding the importance of protecting nature. Show moreįor the Australians who grew up reading Thiele's treasured book, this drama will no doubt be a captivating, special tale for those unfamiliar, it will be more of a challenge to stay engaged. Language is minimal, sex isn't an issue, and themes include compassion, empathy, and teamwork. Expect to see guns in action (hunters shoot and kill birds, and bloody bird carcasses are seen) and adults drinking. That said, the way the boy and the indigenous man meet might be cause for a talk with your kids: The man approaches the boy in a remote area and assures him that he's friendly the next thing you know, the boy brings the man back to his house, where ( phew) the man insists on waiting outside, since the boy's father isn't home. But beautiful relationships shine through, including that of the boy, his dad, and a lonely indigenous man who passes on his tribal customs to the boy. Everyone in the movie is in mourning - all of the main characters have lost parents, wives, and/or children - and the ending is a major heart-wrencher (worse than Old Yeller, but not as harsh as The Yearling). It's a pro-ecological tale about a boy's love for an orphaned pelican and his awakening about the importance of defending wildlife and protecting nature. Leaving that aside, this was a sweet story, one with gorgeous artwork, that I would recommend to anyone looking for tales about children who are reluctant to brush their hair and/or get haircuts, as well as to anyone who admires Khoa Le's artwork.Parents need to know that Storm Boy is a drama based on a children's novella by Colin Thiele that's taught in Australian schools. My only complaint, and I felt the same way about Le's The Cloud Princess - the only other story I have read from this talented author/artist - was with the use of a holographic lenticular cover, which added very little in my opinion. I enjoyed Khoa Le's story here, but it was her artwork that really appealed to me, with its vivid but subtle color palette, its cute (but not too cute) cartoon-style characters, and its general feeling of magic. Of course, in Harry's case the nest and tree are the result of his own refusal to groom properly, making The Boy With the Big Hair more of a didactic cautionary tale than Small's book. Originally published in Switzerland as Noé l'ébouriffé, and translated into English by the San Rafael-based publisher Insight Editions, this appealing little confection of a picture-book reminded me a bit of David Small's classic, Imogene's Antlers, which also featured a child protagonist with something unexpected growing out of their head. and El Espectador, and his first novel, La hojarasca (The Leaf Storm). When a tree begins to grow out of a seed in the doves' nest, and a whole flock of birds take up residence, the young boy has finally had enough, appealing to his mother, who finds the best solution for him, and for the tree. He graduated from the National College for Boys in Zipaquir, a small colonial. Soon the doves have a family, and Harry finds himself exiled from singing class when his avian companions' noise gets to be too much for his teacher. Harry's reluctance to get a haircut leads to trouble in this cautionary tale from Vietnamese author/artist Khoa Le, as a pair of doves, mistaking his untidy head for a likely home, take up residence there and build a nest. Logic Puzzles for iPad and Android Tablets Similarly, if A = B, and B =/= D, then A must not equal D. For example, if A = B, and B = C, then A must equal C. Eventually you will have filled in enough X's and O's on the board that you will then be able to use simple logic to deduce the solution to the puzzle. Furthermore, since every option can only be used once in any given puzzle, you can eliminate the four other options for Bryant in that category (1937, 1946, 1961, 1975) and the four other options for 1971 (Anahi, Jayden, Lauren and Nikolas).Ĭontinue doing this for every clue you're given. Similarly, if you know that Bryant was born in 1971, you can add an O in the appropriate box. If you know, for example, that Lauren wasn't born in 1961, you can add an X in the box where the Lauren column and 1961 row meet. You can eliminate pairs you know aren't true with an X, and pencil in pairs you know are related with an O. The grid allows you to cross-reference every possible option in every category. educated guesses are not required).Ī custom-labeled grid is provided for every puzzle, like the one you see to the right. Each puzzle has only one unique solution, and each can be solved using simple logical processes (i.e. Your goal is to figure out which options are linked together based on a series of given clues. In each puzzle you are given a series of categories, and an equal number of options within each category. Logic puzzles come in all shapes and sizes, but the kind of puzzles we offer here are most commonly referred to as "logic grid" puzzles. Feel free to solve online just for fun, or, for an added challenge, register a free account and compete against thousands of other solvers to make it into our Logic Puzzle Hall of Fame! Welcome to the world's largest web site devoted to logic puzzles! We've got more than 25,000 unique puzzles available for play, both online and the old fashioned way - with pencil and paper. Second, the structural properties of asymmetric synapses in mouse V1 and FC are nearly identical, by stark contrast to the significant differences seen between monkey V1 and LPFC. First, the density of asymmetric synapses does not differ between frontal and visual cortices in either species, but is significantly higher in mouse than in monkey. Analyses of multiple ultrastructural variables revealed four organizational features. We used serial electron microscopy to assess the ultrastructural features of excitatory (asymmetric) synapses in the layers 2-3 (L2-3) neuropil of visual (V1) and frontal (FC) cortices of the adult mouse and compared findings to those in the rhesus monkey (V1 and lateral prefrontal cortex, LPFC). A detailed knowledge of the structure of these synapses in distinct cortical areas and across species is a prerequisite for understanding the anatomical underpinnings of cortical specialization and, potentially, selective vulnerability in neurological disorders. The excitatory glutamatergic synapse is the principal site of communication between cortical pyramidal neurons and their targets, a key locus of action of many drugs, and highly vulnerable to dysfunction and loss in neurodegenerative disease. We conclude that while it is likely that structural changes in dendritic spines are both instigators and results of behavioral changes, improved research tools and methods are needed to experimentally and directly manipulate spine dynamics in order to more empirically delineate the relationship between spine structure and behavior. Although technological advancements have allowed us to better understand the functional relevance of structural changes in dendritic spines that are influenced by environmental stimuli, the role of spine dynamics as an underlying driver or consequence of behavior still remains elusive. We then discuss the existing literature on the temporal and functional relationship between changes in dendritic spines in specific brain regions and changes in specific behaviors mediated by those regions. In this review, we first review the basic structure and function of dendritic spines in the brain, as well as laboratory methods to characterize and quantify morphological changes in dendritic spines. However, it is currently unclear whether structural changes in dendritic spines are primary instigators of changes in specific behaviors, a consequence of behavioral changes, or both. It is clear that the structural plasticity of dendritic spines is related to changes in synaptic efficacy, learning and memory, and other cognitive processes. Both internal and external stimuli influence dendritic spine density and morphology on the order of minutes. Dendritic spines are multifunctional integrative units of the nervous system and are highly diverse and dynamic in nature. Low battery indicator lets you know when it's time to change the battery. Illuminated keypad for easy and quick operation after dark. Keypad has a protective coating to prevent wear patterns. 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It’s no secret that calming music can reduce stress and enhance daily harmony, that’s why you need Calm Radio - the world’s largest selection of relaxing melodies, including sleep sounds, guided mindfulness meditations, nature-fusion, classical music, and the calming sounds of smooth jazz and pop.ĭon’t take it from us, here’s what our listeners have to say about this relaxing classical radio:ĭescribed by The New York Times as “The most popular spiritual author in America”, Eckhart Tolle is just one of our loyal listeners, stating: “I very much enjoy listening to Calm Radio. Domenico Scarlatti (Composer), Maria Tipo (Performer) - Domenico Scarlatti: Sonata in G K124. Calm Radio delivers over 1000 channels of calming sounds, sleep music, sleep sounds, sleep stories, guided meditations, and meditation music that will have you feeling grounded and refreshed in no time. Rupak Kulkarni - Arjun - Tantrakari Ang - Raag Hemant. Create and coach personalized programs for both in-person and virtual clients.Interact with members to enhance their workouts and overall club experience.Execute fitness assessments, guided workouts, and other complimentary services for members.Maintain knowledge of all club services, programs, and products.Market and sell personal training programs to members and/or clients through phone calls, emails, and in-person interactions. Manage and maintain an accurate schedule, inclusive of client appointments, meetings, and open availability within our internal scheduling systems.Build and maintain an active client base.Secure a stronger future and help us redefine the science of fitness and the art of living. Under the guidance of two dedicated managers you will develop and refine an approach to programming, education, business, and financial planning that ensures your Personal Training career is as unlimited as your passion. In addition, Equinox offers all trainers a competitive benefits package including medical, dental and retirement planning options.Īs an Equinox personal trainer your career becomes an empowered lifestyle founded on maximizing both your personal and client performance. We are dedicated to the professional performance of our team and compensate our trainers for their education time.Įquinox offers the highest compensation structure in the industry, with an earning potential of $100K+. For over twenty years EFTI has elevated our trainers to design comprehensive client fitness programs that are safe, effective and results driven. What makes Personal Training with Equinox stand out?Įquinox is proudly recognized as the industry leader in Personal Training expertise, with the first in-house education of its kind through the Equinox Fitness Training Institute. If you are a high performing individual who is passionate about winning and inspiring others then we are excited to discuss career opportunities with you. We value humility and a team approach at every level of the company. We aren't just a company we're a community vested in each other's success. Never following, always leading, living ahead of the moment in fashion, culture and consumer behavior. We are obsessed with what's new, what's now, what's next. We never accept less than 110% to help each other deliver the Equinox experience and enable our members to get great results. We dream big and don't settle for the status quo. We believe that everyone has untapped potential within them and it takes a disruptive approach to unleash it. We are passionate about high performance living and we practice what we preach - investing time in our own health and fitness. Our portfolio of brands is recognized globally with locations within every major city across the United States in addition to London, Toronto, and Vancouver. In addition to Equinox, our other brands, Blink, Pure Yoga, SoulCycle, Equinox Hotels and Equinox Media are all recognized for inspiring and motivating members and employees to maximize life. We restlessly seek what is next for maximizing life - and boldly grow the lifestyle brands and experiences that define it. Equinox Group is a high growth collective of the world's most influential, experiential, and differentiated lifestyle brands. |
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