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OTD: For people who are born with this, developmentally, how does it play out over the long term?OREFICE: This is, I think, a really important aspect of what David and I do in our labs, and what we continue to ask questions about. We’re trying to understand how an abnormal sense of touch impacts the brain and ultimately complex social behaviors.GINTY: We think that touch is the first sense to develop. The first social exchange between a baby and her parents occurs through the sense of touch. You might say that touch is where social development begins. It’s fascinating that a number of studies in humans, nonhuman primates, and other animals have suggested that normal touch is required for the development of normal cognitive processes.In our own mouse studies, we found that if a genetic lesion that causes tactile overreactivity is introduced developmentally in the peripheral nervous system, the animals also exhibit behavioral alterations — a fairly profound anxiety-like behavior, for example, and some aberrant social-interaction behaviors. On the other hand, if the very same genetic lesions are introduced in young adult mice, the animals still exhibit the tactile overreactivity, but they don’t exhibit anxiety-like behavior. So there’s a profound link between developmental touch and tactile reactivity and the acquisition of normal behavior.OTD: So the hope and the hypothesis is presumably that if you can address what’s happening in the peripheral nerves at the right developmental window, you may be able to prevent these kinds of things from appearing down the road.OREFICE: Exactly. We think there’s a critical need for normal tactile input during an early period in development. We’d like to be able to identify that critical window, to treat tactile overreactivity in young children.GINTY: Our thinking is that, even in adulthood, preventing touch overreactivity and thus tactile avoidance and defensiveness would be highly beneficial. But we hypothesize that if we could treat it developmentally, then it might also have a long-term consequence of improving anxiety and possibly even social-interaction behaviors later in life.Professors Lauren Orefice and David Ginty are working to identify possible treatments for the touch hypersensitivity. Caroline Perry/OTD file photoOTD: Do you think a treatment to reduce tactile overreactivity would be taken lifelong, or during critical periods of development?GINTY: We don’t know. Long-term treatment beginning early is a good thing for the animal models of ASD. So, based on our mouse studies, we might speculate that the greatest benefits would come from treating tactile overreactivity over the long term. But that’s really up in the air, because human studies have yet to be done.OREFICE: If we’re speculating, we can imagine that in addition to developmentally improving the sense of touch, a future treatment could also improve acute symptoms in people who are beyond this critical period. Supposing a person knows they’re going to be engaged in a particularly stressful situation, like a cocktail party, perhaps we could dampen these external inputs a little bit for the tactile domain. But we’ve got a long road ahead of us.OTD: As a researcher, how do you know when it’s time to engage with a corporate partner?GINTY: For me, it’s pretty easy. My lab, my postdocs and Ph.D. students, are interested in understanding the basic biology and developing new ideas or principles that emerge from that work, revealing new opportunities. Drug development and all that it entails is not our focus, nor is it our strength. Medchem [medicinal chemistry] to identify chemical variants and drug candidates, testing their activity, doing pharmacodistribution analysis, pharmacodynamics, defining optimal modes of delivery and safety measurements, are all labor-intensive and expensive. Those really specialized details of drug development and optimization are best addressed, at least in our case, by a dedicated company that does this for a living.This is the first time my lab has been able to move something this far that’s this promising. And it took a very talented postdoc in the lab — Lauren — to make it happen. Now, it’s the perfect time for us to move this work out of our labs and the basic biology and discovery realm and move it toward clinical utility with Lab1636.OTD: What else needs to happen to develop your lab’s insights toward benefiting patients?GINTY: Well, there’s a lot of space between identifying a pathophysiological mechanism in a mouse model and understanding whether it’s relevant in a human. This presents a strong case for collaborative efforts between clinician-scientists and basic scientists.If this work is going to be translated, and we’re going to move toward clinical trials, we need to have reliable measurements in humans, especially young kids, so that’s another piece we’re hoping to achieve, with our clinical collaborators.OREFICE: We don’t assume that every person with autism has profound touch overreactivity. So part of what we’re doing now with our collaborators at Beth Israel and Boston Children’s Hospital is trying to find a quantitative, objective metric of somatosensory overreactivity. If we can do that in adults, and also earlier ages, it will help us identify which patients exhibit touch overreactivity and therefore may benefit from this type of treatment.OTD: How did the relationship with Deerfield’s Lab1636 come about? GINTY: The Office of Technology Development here at Harvard is superb. This group was key for moving our project forward because they’re the ones with knowledge of who would be interested in translating the work. They understood what needed to be done to make a compelling case and who, in industry, would have an interest in the work and have the capabilities of moving it forward at a larger scale. They were amazing in terms of making connections and conveying the message of our findings. So in many ways, the technology development office really — it shines here, I’d say.OTD: From your perspective, how has the trajectory looked, from discovery to translation?GINTY: The reason we were able to bring our work to this point is that we have developed a strong capability in genetics, electrophysiology, and using the mouse as a model system, which has allowed us to ask about the locus of dysfunction accounting for touch overreactivity in ASD models: Is it a spinal-cord disorder? Is it a peripheral-nervous-system disorder? Does dysfunction in the brain account for touch overreactivity? What nerve cells or neurons are the ones affected, and why? We’re uniquely poised to ask these kinds of questions. And that’s something we’ve been building toward for 20 years.About three years ago, work by Lauren and her colleagues in the lab made it clear that there may be ways of targeting the peripheral nervous system to reverse touch overreactivity in ASDs. Because of this new therapeutic opportunity, the Blavatnik Biomedical Accelerator and the Q-FASTR funding mechanisms became quite compelling. There was a real translational opportunity arising from the work, which we were excited to pursue. And we were, again, uniquely poised to ask about the potential translatability of the findings. Financial support from the Blavatnik Accelerator and Q-FASTR, and a grant from the Simons Foundation, were critical for helping us define a proof-of-principle pharmacological approach aimed at treating touch overreactivity. These funds allowed the project to move to a point where it became compelling for an outside company to invest the additional resources and capabilities needed to take the work forward. “There are also millions of people with chronic pain, with limited treatment options. Our dependence on opioids has been highly problematic for obvious reasons. Going forward, my lab is taking a deep dive into understanding the molecular biology of all sensory neuron subtypes.” — David Ginty Deerfield commits $100M to create alliance with Harvard Harvard University and Deerfield Management announced today the selection of a first project for funding under the Lab1636 R&D alliance that aims to advance promising innovations from labs across the University toward the clinical development of novel therapeutics. The project arises from the lab of David Ginty, the Edward R. and Anne G. Lefler Professor of Neurobiology in the Blavatnik Institute at Harvard Medical School (HMS) and a Howard Hughes Medical Institute investigator. Lauren Orefice is a former postdoctoral researcher in the Ginty Lab and now assistant professor of genetics at HMS and Massachusetts General Hospital. In a question-and-answer session, Ginty and Orefice discuss their recent progress toward identifying possible treatments for the touch hypersensitivity that often occurs in people with autism spectrum disorders (ASD), and their hope for further innovation in neuroscience.Q&ADavid Ginty and Lauren OreficeOTD: How do people experience touch hypersensitivity?GINTY: Well, the truth is we don’t really know how they experience it. We do know that in certain disorders, including autism, light touch can be highly aversive. In fact, there are several examples of disorders where we see touch overreactivity; a person will react abnormally to what you and I would consider innocuous touch stimuli. For a large number of people with autism, light touch can be aversive, and normal, developmental nurturing touch may also be aversive. We refer to this phenomenon with terms like “tactile avoidance” and “tactile defensiveness.”OREFICE: People with ASD often describe that certain types of clothing can be itchy or difficult to wear. Haircuts can even be really difficult for people to deal with, and there are certain barbers or hairstylists that they’ll go to. Things like inclement weather, heavy rain, can be really overwhelming or frightening for some people. For most of us, we are not typically aware of the fact that we are sitting in a chair, wearing a sweater, and the air conditioning is on, etcetera. But for some people with autism, some of these tactile aspects of their environment feel more present, or more profound, as though the volume is turned up.GINTY: Interestingly, we don’t only see this tactile sensitivity in ASD. In other disorders such as neuropathic pain, which can be caused by chemotherapy, diabetes, or damage affecting the somatosensory system, light touch can also be aversive. It can be painful. “We think there’s a critical need for normal tactile input during an early period in development. We’d like to be able to identify that critical window, to treat tactile overreactivity in young children.” — Lauren Orefice R&D alliance will enable ‘promising innovations to advance beyond their laboratory roots’ Created with $20M gift from K. Lisa Yang and Hock E. Tan, initiative aims to unravel the basic biology of autism and related disorders Harvard to launch center for autism research Related OTD: What are you hopeful about, both for this project and more broadly?GINTY: Well, it’s simple. It would be a dream come true if we could help improve quality of life for people with autism, and for their caregivers as well.OREFICE: It’s difficult, when you’re a basic scientist, to know when you’ve found something that might actually be beneficial for human health. But when you realize that you might be able to help people and improve the way they experience the world, it’s so rewarding. It motivates me to continue the basic research. So as our project moves into Lab1636, my lab and David’s lab will continue to ask more of the basic biological questions to understand the mechanisms through which tactile overreactivity occurs.GINTY: There are also millions of people with chronic pain, with limited treatment options. Our dependence on opioids has been highly problematic for obvious reasons. Going forward, my lab is taking a deep dive into understanding the molecular biology of all sensory neuron subtypes. I’m optimistic that over the next few years, in addition to the strategy for reducing tactile overreactivity, new druggable targets on peripheral neurons will be revealed that will allow us to think of new ways to treat chronic pain. Maybe, over time, this approach will help us move away from our clinical reliance on mu opioid agonists.OTD: Is your perspective any different now having been through this kind of translational experience? David, I hear you talking about finding new druggable targets — is that something that you would have been thinking about five years ago in the same way?GINTY: For me, yes, I think it would have been. But a difference now is that technology has advanced to the point, especially with deep sequencing, that new potential drug targets are made clear for us to see. My experience with this project makes me excited about the possibility of harnessing our knowledge of peripheral-nervous-system biology, and druggable targets on sensory neurons themselves, to define new therapeutic approaches. That feels compelling to me. I think there’s going to be a lot of room for additional partnering over the next five to seven years for parallel approaches, or complementary approaches, not just for treating disorders involving light-touch overreactivity, but for pain sensation too.OREFICE: It has changed my perspective in a lot of ways. When we started these projects in mice about five years ago, we had no idea what we would find. And we’ve been very surprised and encouraged by the findings, the robust observations we’ve made.What it’s taught me most of all is to follow your science, listen to the data, and surround yourself with really intelligent, capable people, including the folks in the Office of Technology Development, who can see your research from different perspectives than how you might normally see it. That can transform everything you’re doing and elevate your work into an entirely new arena.There’s something really special about being at Harvard for this type of work. Being here, in the right environment, and with great collaborators, we’ve been able to find some really interesting biology that we hope will ultimately help humans.
Share Facebook Twitter Google + LinkedIn Pinterest One barrier to weed control on soybean farms has just been lifted. In early November, the Environmental Protection Agency approved a label allowing use of the herbicide dicamba in dicamba-resistant soybean, although only one commercial product received that label. Many farmers anticipate this technology will provide a much-needed method to control weeds that are resistant to multiple herbicides, as well as other difficult-to-control species.“Without question, there are instances and scenarios in which dicamba will improve control of certain weed species, but dicamba will not bring back the ‘good ol’ days’ of POST-only weed control programs in soybean. Current expectations of what this technology can accomplish tend to be a bit more optimistic than what the technology actually will be able to deliver,” said Aaron Hager, University of Illinois weed scientist.Hager expects the technology will work well in a handful of scenarios. For example, dicamba should be effective for glyphosate-resistant horseweed (i.e., marestail) that does not respond to the traditional burndown tankmix of glyphosate and 2,4-D.“The new dicamba label allows up to one pound of dicamba acid-equivalent to be applied prior to planting dicamba-resistant soybean. This can provide better and more consistent control of glyphosate-resistant horseweed compared with 0.5-pound acid-equivalent 2,4-D,” Hager said.It is important to note that although the new label allows soybean to be planted immediately after dicamba application, Hager advises farmers to wait a few days following application before injuring the weeds with the planting operation.Hager also predicts that dicamba will provide good control of tall and ivy-leaf morning glory, as well as common and giant ragweed. “Dicamba certainly can provide better control of herbicide-resistant ragweeds than can glyphosate or ALS inhibitors,” he says.For farmers battling waterhemp, the solution may not be as simple. Most university weed control guides list dicamba as good or very good on waterhemp, but not excellent.“Dicamba can improve control of pigweed species, but it will never be as effective as glyphosate once was,” Hager notes. “Illinois farmers have made great strides toward utilizing more diverse herbicide programs for waterhemp control than they were using a decade ago. We suggest that dicamba should be used in a way that does not reduce this diversity. It is imperative to maintain a diverse weed management approach to prolong the effective utility of dicamba.”Waterhemp populations have evolved resistance to herbicides from six site-of-action groups. According to Hager, resistance to dicamba is not a question of “if”, but “when.”Hager points out some of the restrictions that come with the new dicamba label.“The current label contains several mandates related to the actual spray application procedure that are somewhat unique,” he said. “For instance, there are limitations on boom height, sprayer speed, and nozzle type that applicators must follow.”One of the most significant limitations is the inability to tankmix dicamba with other herbicides. There is an avenue by which other herbicides can be approved for application with dicamba, but if the current label remains unchanged during the 2017 growing season, applicators will be required to apply dicamba alone.“In other words, farmers will make a separate application of dicamba and another application of other needed herbicides,” Hager said.Additional concerns about the new product relate to yield potential of dicamba-resistant soybean and the possibility of particle drift and volatilization. For more information on these issues, please visit The Bulletin.More information will be shared about dicamba use in dicamba-resistant soybean as the product is rolled out. Hager suggests that dicamba will provide a solution to unique weed management challenges, but notes that not all weed management challenges can be met with dicamba.“Other herbicide-resistant crop technologies, such as Liberty Link and Enlist, also can provide solutions and remain viable options for soybean producers. Proper stewardship of all technologies is essential to prolong their effective utilization,” Hager said.
Why Tech Companies Need Simpler Terms of Servic… As of today, businesses and individuals can opt out of recieving paper-based phone books in the mail using a new Website called the National Yellow Pages Consumer Choice & Opt Out Site. Last month, we wrote about a study showing that nearly 70% of adults in the United States “rarely or never” use the phone book, and instead opt to use the Web-based search tools, which are infinitely more convenient and efficient. That research was conducted on behalf on WhitePages.com, who operates BanthePhoneBook.org, a site advocating opt-in-only delivery of phone books.The new opt-out site was created by Yellow Pages Association, the trade organization that represents the publishers of phone books in the United States, signaling an acknowledgement that printing and distributing paper phone books to every household is no longer a sustainable practice. To opt out of recieving the phone book on your door, head to www.yellowpagesoptout.com and register for the site. The registration process requires you to enter your address and phone number, but a note on the page promises that this information won’t be used for any purpose other than the opt out. Tags:#biz#How To A Web Developer’s New Best Friend is the AI Wai… john paul titlow Once registered, you’ll recieve an email with your auto-generated password, which you can then use to log into the site. From there, you can select which phone books you would like to recieve (wishful thinking on their part?) or click the grey “Opt Out of All” button in the lower left and then click “Save Changes.”After opting out, you’ll get a confirmation email listing which phones you’ll be recieving moving forward, if any. 8 Best WordPress Hosting Solutions on the Market Top Reasons to Go With Managed WordPress Hosting Related Posts
From time to time I hear from entrepreneurs who want to grow their revenue without investing in a sales force. Some want to put no money at risk, but they want the results that only come from real investments. They want to be cheap for different reasons, but it’s often a resistance to paying before they get results or because they’ve been burned by salespeople that didn’t produce.Regardless of the reason for not investing, a cheap sales force is really more expensive sales force. You may believe that commission-only salespeople, independent agents, or very low paid salespeople will help you grow your business and reach your goals, but they won’t.Commission OnlyCommission-only is a compensation structure that works in some industries, and mostly only where the sales cycle is short enough to allow the salesperson to be immediately compensated upon making the sale. It isn’t easily applied to long-sales cycle, complex sales where the salesperson might take months to build a pipeline and start winning big deals. Running down the commission-only road costs you time–time that you can’t ever recover.Sometimes independent agents work. But if they represent you along with a lot of other products and services, you have very little control over how much of their effort is really made representing and selling on your behalf. More lost time and more lost opportunities.Very Low Base, High BonusYou may be tempted to try a very low base, very high commission strategy. But getting compensation plans right is more complicated than simply basing the base pay on how little you can get away with paying. If the compensation structure prevents you from acquiring the talent you need to compete and win, it’s an expensive sales force. You’ll spend time, effort, and money without producing the results you need.Don’t believe that this means you should pay any price for the talent you need. Getting the talent you need requires a thoughtful, well planned, and well executed compensation structure. Your budget is a consideration, but there isn’t any way to build a professional sales force without making the necessary investment. The cheaper you are when it comes to investing in a professional sales force, the worse your results will be–if you even produce any results at all.QuestionsWhat is the primary reason some people don’t want to invest in a professional sales force?What are the real costs of an ineffective sales force?How do you afford a sales force when you have real financial constraints?How do you design a compensation structure that produces the real results you need? How much is that driven by real constraints and how much is imagined constraints or personal resistance to paying? Essential Reading! Get my 2nd book: The Lost Art of Closing “In The Lost Art of Closing, Anthony proves that the final commitment can actually be one of the easiest parts of the sales process—if you’ve set it up properly with other commitments that have to happen long before the close. The key is to lead customers through a series of necessary steps designed to prevent a purchase stall.” Buy Now
Typhoon Kammuri accelerates, gains strength en route to PH The Kings took down the Beermen in the 2017 Governors’ Cup Finals, but Cone said it’s an entirely different story in the all-Filipino conference.“They’re actually a different in all-Filipino. I think they’re better all-Filipino than they are with imports. So there’s the difference.” Read Next Google honors food scientist, banana ketchup inventor and war hero Maria Orosa Families in US enclave in north Mexico hold sad Thanksgiving Lady Warriors get newfound joy under Roque Don’t miss out on the latest news and information. Police teams find crossbows, bows in HK university PLAY LIST 01:29Police teams find crossbows, bows in HK university01:35Panelo suggests discounted SEA Games tickets for students02:49Robredo: True leaders perform well despite having ‘uninspiring’ boss02:42PH underwater hockey team aims to make waves in SEA Games01:44Philippines marks anniversary of massacre with calls for justice01:19Fire erupts in Barangay Tatalon in Quezon City Pussycat Dolls set for reunion tour after 10-year hiatus Ginebra’s Greg Slaughter. Photo by Tristan Tamayo/INQUIRER.netRelief hit Tim Cone just moments after Barangay Ginebra went through the wringer in sweeping Rain or Shine in their best-of-three quarterfinals series on Wednesday.But hitting a certain level of comfort won’t last long for Cone and the rest of the Gin Kings, who now face an uphill climb against defending champion San Miguel Beer in a best-of-seven semifinals showdown.ADVERTISEMENT “Wow what a relief. It’s always a big relief to get through the quarters. To me, it’s the hardest series to win, the quarter series,” Cone said after the Gin Kings held on for a 99-91 win over the Elasto Painters.“Now we face the monster. That’s San Miguel. You can refer that to San Miguel or you can refer that to June Mar,” Cone went on.FEATURED STORIESSPORTSWATCH: Drones light up sky in final leg of SEA Games torch runSPORTSLillard, Anthony lead Blazers over ThunderSPORTSMalditas save PH from shutoutEither way, it’s an apt description for the Beermen, who have won the last three all-Filipino conferences and June Mar Fajardo, who is the reigning four-time MVP.“Again, San Miguel, what can you say? They won three championships in a row in this conference for a reason,” Cone said. “You watched San Miguel-Talk ’N Text and Talk ’N Text was really playing good basketball up until that game. They were really turning a hole or a big corner and still, San Miguel, outsteadied them all the way through the game. June Mar came up with 30 plus points.” John Lloyd Cruz a dashing guest at Vhong Navarro’s wedding The top-seeded Beermen entered the semifinals after dumping the KaTropa, 106-93, on Tuesday with Fajardo posting 35 points on 15-of-19 shooting from the field, 11 rebounds and two blocks.Making it doubly hard for the Gin Kings is that Greg Slaughter, their best defender against Fajardo, could still be out early in the series due to an ankle injury.“Our big question mark obviously is whether Greg is gonna play. I would say, if we’re gonna play a day after tomorrow, he won’t play. But if given another day or two, he may play. But we do expect him back some time in the series,” Cone said.“We just hope we don’t fall too far behind without him, whether he can make an impact. That’s the big thing for us, whether Greg can play. That would really help us equalize San Miguel. He’d be the great equalizer.”The semifinals could start as early as Friday and Saturday at the latest depending on the result of the quarterfinals matchup between NLEX and Alaska.ADVERTISEMENT Brace for potentially devastating typhoon approaching PH – NDRRMC Typhoon ‘Tisoy’ threatens Games View comments LATEST STORIES LOOK: Iya Villania meets ‘Jumanji: The Next Level’ cast in Mexico MOST READ
Northern Railway, New Delhi, has invited applications for recruitment of sports personnel in various disciplines. The interested and eligible candidates can apply latest by July 28.Post details:Total posts: 10 postsPost name: Sports PersonnelDiscipline:Cricket (Men): 3 postsWeightlifting: 2 postsVolleyball: 2 postsAthletics (Men): 2 postsAthletics (Women): 1 postEligibility criteria:Educational qualification: The candidates applying for this post should have passed Class 10th.Age limit:The candidates applying for this post should age between 18 and 25 years.Minimum sports achievement:The candidates willing to apply for this post should have represented the country in Commonwealth championships (junior/ senior category) or Asian championships/ Asia Cup (junior/ senior category) or South Asian Federations (SAF) games (senior category) or USIC (world railway) championships (senior category). The candidates should have acquired at least third position in Federation Cup championships (senior category). OrThe candidates should have represented a state or equivalent unit in senior/ youth/ junior national championships. OrThe candidates should have acquired at least third position in senior state championship for all units and district of the state.Selection process:The candidates will be selected on the basis of trial of sports performance and interview.Application fee:The candidates are required to pay an application fee of Rs 40 non refundable including postal charges through crossed postal order or demand draft payable at New Delhi in the name of “Sports Officer/ HQ, Head Quarter Sports Association, Northern Railway, New Delhi”.How to apply:In order to apply, the candidates are required to submit the duly filled application forms at the “Sports Officer/ Headquarter Sports Association, Northern Railway, Baroda House, New Delhi, Room No. 7-G, Annexe-II Building, Baroda House, New Delhi-110001”.advertisementThe candidates are required to send the attested copies of all the required documents/ certificates along. Also, the candidates are required to affix their recent passport-size photograph on the application forms.
AMES, IA – JANUARY 7: A Nike logo is visible on a basketball before the match-up between the Iowa State Cyclones and the Baylor Bears on January 7, 2014 at Hilton Coliseum in Ames, Iowa. (Photo by Matthew Holst/Getty Images)It’s a good time to be a college basketball fan in Iowa. The Iowa Hawkeyes are No. 3 in the AP Poll and No. 4 in the Coaches’ Poll, and Iowa State may be back on the rise after a big home win on Monday night against Kansas. After the game, governor Terry Branstad made his way to the Cyclones locker room. There, he was convinced to hit “the dab,” which is still a dance that people are doing.I’m a bit disappointed that they didn’t get him to “run off on da plug twice,” but its probably for the best.
Managing Director, Wisynco Group, William Mahfood, has given his company’s commitment to continue to invest in the economy. He said that increased investment is what is needed to help the country overcome the existing challenges. “Wisyno is investing a lot as well, so for us, we are committed to Jamaica. I think those companies that continue to invest will see tremendous benefits,” he stated. Mr. Mahfood was speaking at the official opening of a Juici Patties store located at 191 Constant Spring Road, St. Andrew on Thursday, February 21. In commending the franchise holder, the Wisynco Managing Director stated that investments such as these are critical for the development of the country. “The store is opening at a time when so much is happening in our economy so it really does speak volume to the temerity and audaciousness of the investors,” he said. State Minister in the Ministry of Industry, Investment and Commerce, Hon. Sharon Ffolkes-Abrahams, hailed Juici Patties for creating investment and employment opportunities across the island. “Juici Patties is not only directly creating a very significant number of jobs in the food service industry, it is also helping to secure jobs and create employment indirectly, through the local goods and services it purchases,” she said. She noted that a number of the restaurants are operated by franchise holders who, in working with Juici Patties, have developed successful businesses while creating jobs in their communities. “This, from all indications, has been a very successful model,” she said. Franchise holder, Radcliff Knibbs, said he decided to relocate his restaurant from Stony Hill, as the space was too small. He said that over time there will be additions to the offerings and outlay of the new store.The opening of the Constant Spring store brings to 61, the number of Juici Patties establishments across the island.