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Arenado: Manny deal 'really good for baseball'

The baseball field is Rockies third baseman Nolan Arenado's refuge from contract talks. But Tuesday's breaking news -- Manny Machado's 10-year, $300 million contract with the Padres -- made its way onto the field.




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Call for a review of services for people with neurological disorders




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A real opportunity to improve neurology services in England




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Rising drug prices drive US manufacturers’ revenues, analysis finds




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US drug costs are rising faster than overall health spending, officials report




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Australian neuroscientist given two year suspended sentence for falsifying Parkinson's research




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Prescribing sodium oxybate for narcolepsy




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“Impressive results” in stem cell treatment for multiple sclerosis




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Disease modifying therapies for relapsing multiple sclerosis




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Cancer Drugs Fund requires further reform




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Potential role for BCG in treatment of autoimmune diseases




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10 players who you forgot were Blue Jays

Most fans still have a difficult time picturing Jose Bautista wearing anything besides a Blue Jays uniform. In the future, few will be able to name the three organizations Bautista played for in 2018. Some athletes will always be remembered for wearing one uniform in one city, and Bautista is one of those.




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Get ready to watch: MLB.TV available for 2019

Spring Training is imminent, Opening Day is within sight and the big league season isn't complete for fans without a subscription to MLB.TV. The most comprehensive streaming service in professional sports is now available for the 2019 season.




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Here's your guide to Blue Jays Spring Training

The Blue Jays are less than one week away from the start of Spring Training. Here's a brief rundown of everything fans need to know before the Grapefruit League season officially begins.




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Inbox: Who are Blue Jays' sleeper prospects?

What unheralded prospect could break out in 2019? Beat reporter Gregor Chisholm answers that and more in this edition of the Inbox.




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Blue Jays' hope for 2019 lies in the future

The Blue Jays spent the past two years clinging to the past. Now, they're embracing the future.




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Vlad Jr. ready to take center stage this spring

No matter what happens this spring, the player everyone is going to be talking about on a daily basis is Vladimir Guerrero Jr.




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Predicting Blue Jays' Opening Day roster

The start of Spring Training is almost here and it's time for the annual tradition of predicting the Blue Jays' 25-man roster. MLB.com will revisit these projections midway through camp, and then again at the end of Spring Training to see how close we came.




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Buzz precedes Vlad Jr.'s arrival at camp

Vladimir Guerrero Jr. hasn't even reported for duty yet and already he has become the main talking point at Blue Jays Spring Training. General manager Ross Atkins was bombarded with questions about MLB Pipeline's top prospect during his first media availability of the spring on Thursday.




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Sanchez impresses in first spring bullpen

Blue Jays manager Charlie Montoyo was so impressed with Aaron Sanchez's first bullpen session of the spring that it would have been almost impossible to wipe the smile off his face afterwards.




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Axford makes 'ideal' return to Blue Jays for '19

The Blue Jays officially added another veteran to their bullpen Saturday morning by signing right-hander John Axford to a Minor League deal with an invitation to Spring Training. Axford hasn't received any guarantees with the short-term contract, but he is a strong candidate to make Toronto's 25-man roster and head north at the end of camp.




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Reasons for optimism for each MLB club

On this opening week of Spring Training, all 30 Major League teams have one thing in common: optimism. Here's an optimism cheat sheet for each of them.




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GM Atkins responds to comments by Stroman

Blue Jays general manager Ross Atkins declined to get into a back-and-forth with Marcus Stroman on Sunday afternoon, sidestepping criticism of the organization from his right-handed starter.




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Galvis planning to be Blue Jays' regular SS

Freddy Galvis conceded things might eventually change, but the veteran infielder is under the impression that he will be the Blue Jays' everyday shortstop at the start of the season.




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Re: Workplace violence stems from deep rooted problems within the Indian medical system




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Re: Assisted dying bill: Two doctors would need to approve action




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Correspondence on 'Dispute arises over World Professional Association for Transgender Health’s involvement in WHO’s trans health guideline' by Jennifer Block




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Re: Patient involvement in developing clinical guidelines




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Disinformation enabled Donald Trump’s second term and is a crisis for democracies everywhere

Donald Trump did not win the 2020 election, but asserting that he did became a prerequisite for Republicans standing for nomination to Congress or the Senate to win their primaries. An entire party became a vehicle for disinformation.1 Trump did win the 2024 presidential election, and key to that victory was building on the success of that lie. If you control enough of the information ecosystem, truth no longer matters.Another telling example: Haitian migrants in Springfield, Ohio, are not eating cats and dogs. US vice president elect, JD Vance, the source of that claim, admitted as much even as he justified it. “If I have to create stories so that the American media actually pays attention to the suffering of the American people, then that’s what I'm going to do,” he said.2Disinformation in politics is nothing new. History is replete with claims that were fabricated to advance political aims. Although...




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Scarlett McNally: GPs and geriatricians can help to improve shared decision making for surgical patients

At one of my first meetings as an elected council member of the Royal College of Surgeons of England, we approved a report called Access All Ages. It encouraged less ageist thinking and bias among healthcare staff that might lead to them denying older people surgery.1 But sometimes an operation isn’t the best option. Among patients who have surgery, 14% express regret and 15% experience complications, which are at least four times as likely if they’re frail or physically inactive.2 The Centre for Perioperative Care has published information on the importance of exercise before surgery,3 but that alone may not be enough.We need shared decision making,4 including asking patients what matters to them. The public should be primed to ask about BRAN—the benefits, risks, and alternatives to surgery and the likely result from doing nothing.4 A slew of data supports this approach, especially from the POPS initiative (Perioperative Care of...




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Monosynaptic Inputs to Ventral Tegmental Area Glutamate and GABA Co-transmitting Neurons

A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brainwide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus (SC), lateral hypothalamus (LH), midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from the dorsal raphe nucleus, lateral habenula, and VTA. Based on these and prior data, we hypothesized that LH and SC inputs were from glutamatergic neurons. Optical activation of glutamatergic LH neurons activated VTA VGluT2+VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic SC neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high frequency and resulted in head rotation and arrested ambulatory behavior (freezing). Stimulation of glutamatergic LH neurons, but not glutamatergic SC neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity and inhibition of LH glutamatergic neurons disrupted VTA VGluT2+VGaT+ tailshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally salient outcomes.




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Behavioral and Neural Mechanisms of Face-Specific Attention during Goal-Directed Visual Search

Goal-directed visual attention is a fundamental cognitive process that enables animals to selectively focus on specific regions of the visual field while filtering out irrelevant information. However, given the domain specificity of social behaviors, it remains unclear whether attention to faces versus nonfaces recruits different neurocognitive processes. In this study, we simultaneously recorded activity from temporal and frontal nodes of the attention network while macaques performed a goal-directed visual search task. V4 and inferotemporal (IT) visual category-selective units, selected during cue presentation, discriminated fixations on targets and distractors during the search but were differentially engaged by face and house targets. V4 and IT category-selective units also encoded fixation transitions and search dynamics. Compared with distractors, fixations on targets reduced spike–LFP coherence within the temporal cortex. Importantly, target-induced desynchronization between the temporal and prefrontal cortices was only evident for face targets, suggesting that attention to faces differentially engaged the prefrontal cortex. We further revealed bidirectional theta influence between the temporal and prefrontal cortices using Granger causality, which was again disproportionate for faces. Finally, we showed that the search became more efficient with increasing target-induced desynchronization. Together, our results suggest domain specificity for attending to faces and an intricate interplay between visual attention and social processing neural networks.




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Encoding of Vibrotactile Stimuli by Mechanoreceptors in Rodent Glabrous Skin

Somatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in the rodent glabrous skin has received scant attention, unlike in primates where the glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal patterning of LTMR spikes. Rate coding depends on the probability of a spike occurring on each stimulus cycle (reliability), whereas temporal coding depends on the timing of spikes relative to the stimulus cycle (precision). Using in vivo extracellular recordings in male rats and mice of either sex, we measured the reliability and precision of LTMR responses to tactile stimuli including sustained pressure and vibration. Similar to other species, rodent LTMRs were separated into rapid-adapting (RA) or slow-adapting based on their response to sustained pressure. However, unlike the dichotomous frequency preference characteristic of RA1 and RA2/Pacinian afferents in other species, rodent RAs fell along a continuum. Fitting generalized linear models to experimental data reproduced the reliability and precision of rodent RAs. The resulting model parameters highlight key mechanistic differences across the RA spectrum; specifically, the integration window of different RAs transitions from wide to narrow as tuning preferences across the population move from low to high frequencies. Our results show that rodent RAs can support both rate and temporal coding, but their heterogeneity suggests that coactivation patterns play a greater role in population coding than for dichotomously tuned primate RAs.




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Monocyte Invasion into the Retina Restricts the Regeneration of Neurons from Müller Glia

Endogenous reprogramming of glia into neurogenic progenitors holds great promise for neuron restoration therapies. Using lessons from regenerative species, we have developed strategies to stimulate mammalian Müller glia to regenerate neurons in vivo in the adult retina. We have demonstrated that the transcription factor Ascl1 can stimulate Müller glia neurogenesis. However, Ascl1 is only able to reprogram a subset of Müller glia into neurons. We have reported that neuroinflammation from microglia inhibits neurogenesis from Müller glia. Here we found that the peripheral immune response is a barrier to CNS regeneration. We show that monocytes from the peripheral immune system infiltrate the injured retina and negatively influence neurogenesis from Müller glia. Using CCR2 knock-out mice of both sexes, we found that preventing monocyte infiltration improves the neurogenic and proliferative capacity of Müller glia stimulated by Ascl1. Using scRNA-seq analysis, we identified a signaling axis wherein Osteopontin, a cytokine highly expressed by infiltrating immune cells is sufficient to suppress mammalian neurogenesis. This work implicates the response of the peripheral immune system as a barrier to regenerative strategies of the retina.




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A Prefrontal->Periaqueductal Gray Pathway Differentially Engages Autonomic, Hormonal, and Behavioral Features of the Stress-Coping Response

The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes. Optogenetic excitation of the rostral medial prefrontal cortex (mPFC) input to the ventrolateral periaqueductal gray (vlPAG) decreased passive behavior (immobility), attenuated the glucocorticoid hormone response, but did not prevent arterial pressure and heart rate increases associated with rats’ active behavioral (defensive burying) engagement during the SPDB. In contrast, inhibition of the same pathway increased behavioral immobility and attenuated hemodynamic output but did not affect glucocorticoid increases. Further analyses confirmed that hemodynamic increments occurred preferentially during active behaviors and decrements during immobility epochs, whereas pathway manipulations, regardless of the directionality of effect, weakened these correlational relationships. Finally, neuroanatomical evidence indicated that the influence of the rostral mPFC->vlPAG pathway on coping response patterns is mediated predominantly through GABAergic neurons within vlPAG. These data highlight the importance of this prefrontal->midbrain connection in organizing stress-coping responses and in coordinating bodily systems with behavioral output for adaptation to aversive experiences.




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Deciphering Peripheral Taste Neuron Diversity: Using Genetic Identity to Bridge Taste Bud Innervation Patterns and Functional Responses

Peripheral taste neurons exhibit functional, genetic, and morphological diversity, yet understanding how or if these attributes combine into taste neuron types remains unclear. In this study, we used male and female mice to relate taste bud innervation patterns to the function of a subset of proenkephalin-expressing (Penk+) taste neurons. We found that taste arbors (the portion of the axon within the taste bud) stemming from Penk+ neurons displayed diverse branching patterns and lacked stereotypical endings. The range in complexity observed for individual taste arbors from Penk+ neurons mirrored the entire population, suggesting that taste arbor morphologies are not primarily regulated by the neuron type. Notably, the distinguishing feature of arbors from Penk+ neurons was their propensity to come within 110 nm (in apposition with) different types of taste-transducing cells within the taste bud. This finding is contrary to the expectation of genetically defined taste neuron types that functionally represent a single stimulus. Consistently, further investigation of Penk+ neuron function revealed that they are more likely to respond to innately aversive stimuli—sour, bitter, and high salt concentrations—as compared with the full taste population. Penk+ neurons are less likely to respond to nonaversive stimuli—sucrose, umami, and low salt—compared with the full population. Our data support the presence of a genetically defined neuron type in the geniculate ganglion that is responsive to innately aversive stimuli. This implies that genetic expression might categorize peripheral taste neurons into hedonic groups, rather than simply identifying neurons that respond to a single stimulus.




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The Role of the Rat Prefrontal Cortex and Sex Differences in Decision-Making

The prefrontal cortex is critical for decision-making across species, with its activity linked to choosing between options. Drift diffusion models (DDMs) are commonly employed to understand the neural computations underlying this behavior. Studies exploring the specific roles of regions of the rodent prefrontal cortex in controlling the decision process are limited. This study explored the role of the prelimbic cortex (PLC) in decision-making using a two-alternative forced-choice task. Rats first learned to report the location of a lateralized visual stimulus. The brightness of the stimulus indicated its reward value. Then, the rats learned to make choices between pairs of stimuli. Sex differences in learning were observed, with females responding faster and more selectively to high-value stimuli than males. DDM analysis found that males had decreased decision thresholds during initial learning, whereas females maintained a consistently higher drift rate. Pharmacological manipulations revealed that PLC inactivation reduced the decision threshold for all rats, indicating that less information was needed to make a choice in the absence of normal PLC processing. μ-Opioid receptor stimulation of the PLC had the opposite effect, raising the decision threshold and reducing bias in the decision process toward high-value stimuli. These effects were observed without any impact on the rats’ choice preferences. Our findings suggest that PLC has an inhibitory role in the decision process and regulates the amount of evidence that is required to make a choice. That is, PLC activity controls "when," but not "how," to act.




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Neural Predictors of Fear Depend on the Situation

The extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fear-evocative situations including fear of heights, spiders, and social threats. Participants (n = 21; 10 females and 11 males) viewed ~20 s clips depicting spiders, heights, or social encounters and rated fear after each video. Searchlight multivoxel pattern analysis was used to identify whether and which brain regions carry information that predicts fear experience and the degree to which the fear-predictive neural codes in these areas depend on or generalize across the situations. The overwhelming majority of brain regions carrying information about fear did so in a situation-dependent manner. These findings suggest that local neural representations of fear experience are unlikely to involve a singular pattern but rather a collection of multiple heterogeneous brain states.




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Orbitofrontal Cortex Mediates Sustained Basolateral Amygdala Encoding of Cued Reward-Seeking States

Basolateral amygdala (BLA) neurons are engaged by emotionally salient stimuli. An area of increasing interest is how BLA dynamics relate to evolving reward-seeking behavior, especially under situations of uncertainty or ambiguity. Here, we recorded the activity of individual BLA neurons in male rats across the acquisition and extinction of conditioned reward seeking. We assessed ongoing neural dynamics in a task where long reward cue presentations preceded an unpredictable, variably time reward delivery. We found that, with training, BLA neurons discriminated the CS+ and CS– cues with sustained cue-evoked activity that correlated with behavior and terminated only after reward receipt. BLA neurons were bidirectionally modulated, with a majority showing prolonged inhibition during cued reward seeking. Strikingly, population-level analyses revealed that neurons showing cue-evoked inhibitions and those showing excitations similarly represented the CS+ and behavioral state. This sustained population code rapidly extinguished in parallel with conditioned behavior. We next assessed the contribution of the orbitofrontal cortex (OFC), a major reciprocal partner to the BLA. Inactivation of the OFC while simultaneously recording in the BLA revealed a blunting of sustained cue-evoked activity in the BLA that accompanied reduced reward seeking. Optogenetic disruption of BLA activity and OFC terminals in the BLA also reduced reward seeking. Our data indicate that the BLA represents reward-seeking states via sustained, bidirectional cue-driven neural encoding. This code is regulated by cortical input and is important for the maintenance of vigilant reward-seeking behavior.




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Cycling to the unreached

Staff from OM SportsLink and Campus Crusade for Christ cycled from Pretoria to Cape Town to minister to people in rural villages along the way.




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Preparing for missions

Engage, OM South Africa’s bi-annual conference, provides a challenge and a channel for joining missions with OM.




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Even when you’re tired, God works

God sustained MDT participant David, who found it difficult co-leading his short-term outreach when he wasn't doing so well himself.




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There's more to life than rugby

For the past two years OM South Africa SportsLink has attended a prestigious rugby tournament to spread the good news to players, coaches and staff.




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Kids challenged to share the gospel

The AIDS Hope team encourages children in their afterschool program in Mamelodi to share the gospel with the community.




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Kids' reading club

Marleen was challenged to create reading curriculum for kids by what she saw while climbing Mount Everest in Nepal.




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Dabbling in the office of dreams

For the OM Africa communications and media team, the latest and greatest thing is a duck.




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Sharing about freedom

Three patients in a hospital for drug addicts pray a prayer of repentance after hearing testimonies from students in OM Russia’s missions school.




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About OM Russia’s Student Christian Centre

OM Russia’s Student Christian Centre, in partnership with the local Evangelical Church, reaches universities in Novosibirsk. The project leader shares about plans for this year.




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‘Always Ready!’

God uses three OM Russia Discipleship Centre students to bring hope and help to members of a remote church in Siberia.




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Trans-Siberian adventure!

OM Russia's short-term outreach team travels across Russia sharing about Christ with as many travellers as possible.