Here’s how I see things now:HittersLocks (11): Will Smith, Russell Martin, David Freese, Max Muncy, Corey Seager, Justin Turner, Cody Bellinger, Joc Pederson, A.J. Pollock, Chris Taylor, Kiké HernandezOn the bubble (3 players for 2 spots): Matt Beaty, Gavin Lux, Edwin RiosNot happening (3): Jedd Gyorko, Kristopher Negron, Austin Barnes Newsroom GuidelinesNews TipsContact UsReport an Error Editor’s note: This is the Friday, Sept. 27 edition of the Inside the Dodgers newsletter. To receive the newsletter in your inbox, sign up here.The Dodgers have clinched the number-1 seed on the National League side of the playoff bracket. They won’t know their first-round opponent until next Tuesday’s wild card game is complete.Dave Roberts has said the final roster spots depend on the Dodgers’ first-round opponent. I tend to believe him. The Nationals, for example, are a largely capable group of hitters against left-handed pitchers. The Cardinals are not. For a relief pitcher on the bubble – right-hander Dylan Floro or left-hander Caleb Ferguson, for example – the opponent could dictate whether or not he watches from the Dodgers’ bullpen or from Camelback Ranch.With that in mind, I wanted to take another look at the Dodgers’ projected 25-man NLDS roster. Is anyone actually auditioning for something this weekend in San Francisco? PitchersLocks (9): Clayton Kershaw, Walker Buehler, Hyun-Jin Ryu, Rich Hill, Kenley Jansen, Pedro Baez, Kenta Maeda, Joe Kelly, Julio UríasOn the bubble: (6 players for 3 spots): Ross Stripling, Dustin May, Tony Gonsolin, Adam Kolarek, Caleb Ferguson, Casey Sadler, Dylan FloroNot happening (2): Josh Sborz, Yimi GarciaFirst, some injury-related caveats.1. Hill has one more start (Sunday against the Giants) to prove his knee can handle 2 or 3 innings on a mound. I’m only calling Hill a “lock” on the premise that his knee holds up. If it doesn’t, I imagine the Dodgers would plug Urías into his spot. Maybe Gonsolin or Stripling. The ability to pitch 2-3 innings seems to be the main qualifier for whomever starts Game 4. It’ll be a bullpen game regardless of who pitches and when.2. We can only take Kelly and Roberts at their word when they say Kelly is going to be ready for the postseason. If you buy that, then Kelly’s next appearance is not a test of his health, but a tuneup. If it is a test – of what, neither will say – and Kelly does not pass, then another short-inning reliever would need to take his place.3. Seager’s latest hamstring injury is a good omen for Lux’s chances of making the final cut. Turner’s back injury might help Beaty. If some roster “insurance” for Seager or Turner is unwarranted, both Lux and Beaty probably make it anyway.As for where the few remaining “position battles” stand …BenchThe first time I ran this exercise, I nearly penciled in Beaty and Lux as locks. (Lux as locks. Heh.) I almost did it again, in spite of how they’ve hit lately. Beaty is 1 for his last 20. Lux is 1 for his last 16. If Scott Elbert and Brian Dozier can get postseason roster spots, these guys can too, though I wonder if Edwin Rios’ surprise September call-up (3 for 9, two HRs) has changed the internal conversations at all. All three are left-handed hitters with pop. Rios’ lack of positional versatility might off-set his value as a pinch hitter, so even a 470-foot home run into San Francisco Bay might not get Rios in at this point.BullpenThere are a lot of wrinkles here. Some if-then scenarios. Let’s start with the big “if.”Roberts asked Kolarek and Kenta Maeda to pitch the ninth inning of a 1-0 win Thursday because Jansen wasn’t allowed to pitch three days in a row. For those of you who just tuned in, you might think the manager is open to using that ninth-inning committee in similar situations in October. Dave Roberts says he’s open to a lot of things, but ninth-inning committees aren’t one.Before Wednesday, Jansen had not converted save opportunities on consecutive days since May. While closing the Dodgers’ first two wins over the Padres, Jansen looked downright normal. If back-to-back scoreless innings against the Padres counts as “earning the closer’s job,” then maybe Jansen is not the question mark I envisioned three weeks ago. But that’s a big “if.” It’s the big “if.” Right now, with three games remaining, Jansen, Maeda and Kolarek all look like necessary ninth-inning options. That means they’re all in.In his seven relief appearances since Sept. 7, May has used his two-seam fastball to neuter right-handed hitters, and his four-seamer to neuter lefties. The two pitches regularly clock in at 95-99 mph. His low-90s cutter has been an effective if unconventional “off-speed pitch” in short situations. For the Dodgers, this was the best-case scenario.May has adjusted to his new role. Kolarek has been dominating his, for the most part. If Kelly is healthy – also a best-case scenario for the Dodgers – that leaves one bullpen job for Gonsolin, Stripling, Ferguson, Sadler and Floro. Woof.I think we can safely peg Sadler and Floro as the longshots here. They’re essentially right-handed specialists, Floro more so than Sadler. Floro is the bigger liability against left-handers, while Sadler’s 2.23 ERA looks a bit deceiving. They’re both behind Maeda, Baez and Kelly in the bullpen pecking order. Those three all offer the added bonus of postseason experience, the ability to pitch multiple innings, and a better chance of retiring the occasional lefty. I think Sadler and Floro are out.Ferguson has emerged as an unusually versatile relief pitcher. Since Aug. 1, the left-hander is almost evenly dominant against lefties and righties. I could make the case for him to take Kolarek’s role, but Roberts seems content with what he’s gotten from his designated LOOGY. If the Dodgers weren’t planning to throw their entire bullpen at Game 4, Ferguson would have an even better case than Floro or Sadler to be the final pick.As things stand, however, I imagine Roberts and Andrew Friedman will want to guard against the danger of a bullpen game that runs too long. Asking three or more pitchers to tag-team six or seven innings isn’t monumental. If Game 4 is tied after nine innings, however, managing workloads becomes a bit dicey – for that game and for the remainder of the series. Stripling and Gonsolin have pitched up to five innings as recently as August. Ferguson hasn’t completed three innings in a game all year. That’s why I think Ferguson draws the short straw here – only because Hill couldn’t stay healthy enough in September to start 5+ innings in the NLDS.The two remaining options are both attractive. Despite a shaky first inning Wednesday, Stripling has been reliable overall this month. Gonsolin has limited his September opponents to a miniscule .504 OPS, but seven walks in 11 innings might not cut it. Throw in Stripling’s experience and I give him a slight edge for the final roster spot over Gonsolin.Whether the Dodgers draw the Cardinals, Brewers or Nationals in the first round could determine who gets the final bullpen spot. So could the health of Hill and Kelly. Gonsolin has had two poor innings all month: one last Wednesday against the Rays, and another Sept. 7 against the Giants. Maybe one good outing by Gonsolin and one bad outing by Stripling this weekend shifts the balance.There’s a broader takeaway here, too. Back on Aug. 1, fans were up in arms when the Dodgers failed to consummate a trade for Pirates closer Felipe Vazquez. Friedman chose to build a new bullpen out of his existing parts instead. At a distance, that might have sounded like a hope and a prayer. Yet since Aug. 1, the Dodgers’ bullpen has been one of the best in baseball just about any way you slice it. Their internal options for October are bountiful, and Vazquez is in jail. What a difference two months makes.-J.P.Editor’s note: Thanks for reading the Inside the Dodgers newsletter. To receive the newsletter in your inbox, sign up here.More readingBelli or Yeli? – FanGraphs’ Craig Edwards declared the National League MVP race “too close to call.”Who’s your padre – Clayton Kershaw’s final regular season start offered a compelling audition for Game Whatever.Pescascarian diet – Walker Buehler says he won’t eat anything that swims.
Source:https://www.iospress.nl/ios_news/early-treatment-with-nusinersen-can-mean-better-outcomes-for-babies-with-spinal-muscular-atrophy/ Jul 17 2018Spinal muscular atrophy (SMA) is a genetic disease that affects motor neurons in the spinal cord, resulting in muscle atrophy and widespread weakness that eventually impair swallowing and breathing. A new study in the Journal of Neuromuscular Diseases finds that children with SMA type 1 can achieve improvements in motor function after six months of treatment with the drug nusinersen, particularly when treatment began before seven months of age. These findings highlight the importance of early detection of SMA through newborn screening.”Our findings add to the increasing body of evidence that early diagnosis and initiation of treatment is fundamental for patients with infantile-onset spinal muscular atropy,” explained lead investigator Janbernd Kirschner, MD, of the Department of Neuropediatrics and Muscle Disorders, Medical Center, Faculty of Medicine, University of Freiburg, and Coordinator of the TREAT-NMD Clinical Trial Coordination Centre (CTCC), Freiburg (Germany).SMA type 1 is the most common and also most severe subtype of SMA. After diagnosis infants with SMA type 1 rarely achieve improvements of motor function or attain motor developmental milestones. Within the last few years, there has been a promising approach for the development of novel drugs intervening the pathophysiology of SMA. Among these, nusinersen is the first drug specifically approved to treat SMA. Prior to approval in Europe, nusinersen was provided to patients with SMA type 1 within an Expanded Access Program (EAP). In contrast to the previous clinical trials, children of different age groups and different stages of the disease were treated with nusinersen within the EAP.The current prospective, open-label study conducted in Germany reports outcomes from 61 children with SMA type 1 treated with nusinersen between November 2016 and June 2017 who met EAP guidelines. Patients ranged in age from a few months to almost 8 years. Symptoms generally appeared within the first three months of life and most babies were diagnosed before six months of age. Prior to treatment, more than jhalf of the children required ventilation support, 20% had already undergone a tracheostomy, and more than half required a feeding tube.Related StoriesChaos in the house and asthma in children – the connectionGenetic contribution to distractibility helps explain procrastinationWhy Mattresses Could be a Health Threat to Sleeping ChildrenAlthough improvements in motor function are not expected within the natural course of the disease, the researchers observed improvements in motor function after six months of nusineresen therapy in many patients, and 34% of the patients achieved new motor developmental milestones. The response to treatment strongly correlated with age at onset of treatment. Overall, greater improvements were seen in children who began treatment at seven months or younger compared to those who started treatment after seven months. Improvements could still be seen in patients who started therapy between two and four years of age, although the magnitude of the changes was less than those for infants. Despite six months of treatment, none of the children were able to stand or walk independently, and many still required ventilator support and tube feeding.The findings of this study add to the increasing body of evidence that early diagnosis and initiation of treatment are fundamental for patients with infantile onset spinal muscular atrophy highlighting the importance of the implementation of a newborn screening. “We have evidence that there is a critical therapeutic time window for delivery of SMN-targeted therapies,” noted Dr. Kirschner. “The implementation of newborn screening for SMA is crucial to allow pre-symptomatic diagnosis.Based on the results of this study, the SMArtCARE project aims to collect further data of all SMA patients to evaluate outcomes in a broader spectrum of SMA, the effect of treatment after prolonged treatment periods, and also to what extent changes in motor function affect patients’ and caregivers’ quality of life.SMA is caused by mutations in the survival motor neuron (SMN) 1 gene, which codes for survival motor neuron protein. This leads to loss of function. The SMN 1 gene is located on chromosome 5q13. Nusinersen, the first drug to be approved for SMA, is an antisense oligonucloetide which leads to increased expression of more full-length and functional SMN protein by functionally converting the SMN2 gene into the SMN1 gene. Nusinersen is injected into the spinal canal to allow it to distribute to the central nervous system.