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  • Spatiotemporal subtypes of brain and spinal cord atrophy in neuromyelitis optica spectrum disorders and multiple sclerosis | BMC Medicine

    Spatiotemporal subtypes of brain and spinal cord atrophy in neuromyelitis optica spectrum disorders and multiple sclerosis | BMC Medicine

    Demographic data

    Totally 1,774 subjects were initially enrolled, including 1,082 HCs, 290 AQP4 antibody positive neuromyelitis optica spectrum disorders (AQP4 + NMOSD) and 402 multiple sclerosis (MS) cases. Fourteen HCs, 6 AQP4 + NMOSD and 6 MS were excluded due to a history of other CNS disease. Three HCs, 6 AQP4 + NMOSD and 5 MS were excluded due to poor image quality. Finally, 1,734 subjects, including 1,065 HCs (age = 45 [31, 54], median [interquartile range, IQR] female percentage = 566/1,065), 278 AQP4 + NMOSD (age = 43 [31, 53] years; female percentage = 256/278) and 391 MS (age = 34 [27, 42] years, female percentage = 264/391) were included in this study (Table 1).

    Brain and spinal cord spatiotemporal atrophy subtypes in AQP4 + NMOSD and MS

    Three AQP4 + NMOSD atrophy subtypes were identified (Figs. 1 and 2 and Additional file 1: Fig. S1): (1) cortical atrophy subtype (NMOSD-C, n = 87, 31.3%), with gradual atrophy of cortical, subcortical and cerebellar GM, spinal cord and brainstem across all stages; (2) spinal cord atrophy subtype (NMOSD-SC, n = 58, 20.9%), with gradual atrophy of the spinal cord, brainstem, subcortical, cerebellar and cortical GM across all stages; and (3) cerebellar atrophy subtype (NMOSD-CE, n = 26, 9.4%), with gradual atrophy of cerebellar GM and WM, and brainstem in early stages, and subcortical and cortical GM, cerebral WM and spinal cord in late stages. Additionally, 107 (38.5%) AQP4 + NMOSD were “normal-appearing” (NMOSD-NA).

    Fig. 1

    SuStaIn subtypes of AQP4 + NMOSD and MS. a, Ternary plot showing the probability of each individual to be classified in a subtype. Dots are labeled by final subtype classification. b, Averaged z-score mappings of brain and spinal cord volumes for each disease and its subtypes. The positive Z-score, indicating atrophy compared to healthy controls, is used for visualization. c, Brain and spinal cord regional mapping of differences (T value) between one subtype and all other subtypes using OLS linear models with adjustment for SuStaIn stage. AQP4, aquaporin 4; NMOSD, neuromyelitis optica spectrum disorders; MS, relapsing–remitting multiple sclerosis; NMOSD-C, cortical atrophy leading subtype of AQP4 antibody positive (AQP4 +) NMOSD; NMOSD-SC, spinal cord atrophy leading subtype of AQP4 + NMOSD; NMOSD-CE, cerebellar atrophy leading subtype of AQP4 + NMOSD; MS-C, cortical atrophy leading subtype of MS; MS-SC, spinal cord atrophy subtype of MS; MS-DGM, deep gray matter atrophy subtype of MS

    Fig. 2
    figure 2

    SuStaIn stages of AQP4 + NMOSD and MS subtypes. Progression of each subtype through SuStaIn stages. Each image is a mean of individuals classified for the listed stages. Here stages from 1–20 are displayed, comprising a majority of subtypeable cases (224 out of 268 for MS and 168 out of 171 for AQP4 + NMOSD). AQP4, aquaporin 4; NMOSD, neuromyelitis optica spectrum disorders; MS, relapsing–remitting multiple sclerosis; NMOSD-C, cortical atrophy leading subtype of AQP4 antibody positive (AQP4 +) NMOSD; NMOSD-SC, spinal cord atrophy leading subtype of AQP4 + NMOSD; NMOSD-CE, cerebellar atrophy leading subtype of AQP4 + NMOSD; MS-C, cortical atrophy leading subtype of MS; MS-SC, spinal cord atrophy subtype of MS; MS-DGM, deep gray matter atrophy subtype of MS

    Three MS atrophy subtypes were also identified (Figs. 1 and 2 and Additional file 1: Fig. S1): (1) MS-C subtype (n = 72, 18.4%), with gradual atrophy of cortical and subcortical GM, cerebral WM and brainstem in early stages, and spinal cord, and cerebellum in late stages; (2) MS-SC subtype (n = 115, 29.4%), with gradual atrophy of the spinal cord, brainstem, subcortical GM, cerebral and cerebellar WM, cerebral and cerebellar GM across the stages; and (3) Deep gray matter atrophy subtype (MS-DGM, n = 81, 20.7%), with gradual atrophy of subcortical GM, cerebral WM and GM, brainstem, cerebellar WM and spinal cord across all stages. Additionally, 123 (31.4%) MS cases were “normal-appearing” (MS-NA).

    Subtype stability and stage progression of AQP4 + NMOSD and MS subtypes

    In AQP4 + NMOSD (Fig. 3c), 20 (20/28, 71.4%) individuals exhibited the same subtype at both baseline and follow-up or progressed from NA to a subtype. Disease stability after excluding individuals classified as NA at baseline and follow-up was found in 80% of cases (12/15).

    Fig. 3
    figure 3

    Clinical and MRI characteristics, stability and stage association of AQP4 + NMOSD and MS atrophy subtypes. a Clinical characteristics of atrophy subtypes. b MRI characteristics of atrophy subtypes. c Subtype stability and stage progression of NMOSD and MS subtypes using longitudinal scans. d Clinical and MRI associations of atrophy stage. AQP4, aquaporin 4; NMOSD, neuromyelitis optica spectrum disorders; MS, multiple sclerosis; NMOSD-C, cortical atrophy leading subtype of AQP4 antibody positive (AQP4 +) NMOSD; NMOSD-SC, spinal cord atrophy leading subtype of AQP4 + NMOSD; NMOSD-NA, “normal-appearing” AQP4 + NMOSD; NMOSD-CE, cerebellar atrophy leading subtype of AQP4 + NMOSD; MS-NA, “normal-appearing” MS; MS-C, cortical atrophy leading subtype of MS; MS-SC, spinal cord atrophy subtype of MS; MS-DGM, deep gray matter atrophy subtype of MS; WMH, white matter hyperintensity; CVLT, California Verbal Learning Test; Brief BVMT, Visuospatial Memory Test-Revised; PASAT, Paced Auditory Serial Addition Test; SDMT, Symbol Digit Modalities Test; COWAT, Controlled Oral Word Association Test; EDSS, Expanded Disability Status Scale

    In MS (Fig. 3c), 30 (30/33, 90.9%) individuals exhibited the same subtype at both baseline and follow-up or progressed from NA to a subtype. Disease stability after excluding individuals classified as NA at baseline and follow-up was found in 84.2% of cases (16/19).

    Clinical and MRI features of AQP4 + NMOSD and MS atrophy subtypes

    In AQP4 + NMOSD (Fig. 3a and b), compared with NMOSD-NA, NMOSD-C had higher EDSS score, lower COWAT score, larger choroid plexus volume, and lower FAs of cerebral WM and brainstem. Compared with NMOSD-NA, NMOSD-SC had a higher number of relapses, lower BVMT score, larger choroid plexus volume, and lower cerebral WM-FA. Compared with NMOSD-NA, NMOSD-CE only had lower brainstem FA. In between atrophy subtype comparisons, NMOSD-C showed lower COWAT score than NMOSD-SC and NMOSD-CE. NMOSD-SC showed lower BVMT score than NMOSD-C. NMOSD-CE had higher cerebellar GM-fALFF than NMOSD-SC. Details are found in Additional file 1: Supplementary Results. Additional analyses by stratifying patients according to their primary clinical syndromes were presented in Additional file 1: Fig. S6. Preliminary subgroup analyses showed similar trends with the main findings when the NMOSD patients were stratified by optic neuritis and myelitis, indicating weak associations between these clinical syndromes and specific atrophy subtypes.

    In MS (Fig. 3a and b), compared with MS-NA, MS-C had lower PASAT and SDMT scores, and larger choroid plexus volume. Compared with MS-NA, MS-SC had a higher number of relapses, higher EDSS score, lower PASAT score, longer disease duration, larger choroid plexus volume, and lower FAs of cerebral WM, cerebellar WM and brainstem. Compared with MS-NA, MS-DGM had higher EDSS score, lower PASAT score, longer disease duration, larger choroid plexus volume, and lower cerebral and cerebellar WM-FAs. In between atrophy subtype comparisons, MS-SC had a higher number of relapses, and lower cerebral and cerebellar WM-FAs compared with MS-C and MS-DGM, while MS-C had lower SDMT score than MS-SC. Details are found in Additional file 1: Supplementary Results.

    Stage associations in AQP4 + NMOSD and MS atrophy subtypes

    In AQP4 + NMOSD, no differences in stages were observed among NMOSD-C, NMOSD-SC and NMOSD-CE. Atrophy stage in NMOSD-C was correlated with EDSS score (R = 0.25, p = 0.0031, pFDR = 0.022), number of relapses (R = 0.18, p = 0.047, pFDR = 0.21) and choroid plexus volume (R = 0.20, p = 0.0072, pFDR = 0.041) (Fig. 3d).

    In MS, no differences in stages were observed among MS-C, MS-SC and MS-DGM. Atrophy stage in MS-C was correlated with age (R = 0.20, p = 0.014, pFDR = 0.39), disease duration (R = 0.45, p < 0.0001, pFDR < 0.0001), relapse (R = 0.35, p = 0.0026, pFDR = 0.0095), WMH volume (R = 0.24, p = 0.0027, pFDR =  = 0.0095) and choroid plexus volume (R = 0.43, p < 0.0001, pFDR < 0.0001). Atrophy stage in MS-SC was correlated with disease duration (R = 0.16, p = 0.014, pFDR = 0.039), EDSS score (R = 0.15, p = 0.022, pFDR = 0.057), PASAT score (R = −0.21, p = 0.032, pFDR = 0.074), SDMT score (R = −0.38, p = 0.035, pFDR = 0.079), WMH volume (R = 0.17, p = 0.0063, pFDR = 0.020) and choroid plexus volume (R = 0.23, p = 0.00036, pFDR = 0.0014). Atrophy stage in MS-DGM was correlated with disease duration (R = 0.18, p = 0.026, pFDR = 0.065), EDSS score (R = 0.16, p = 0.041, pFDR = 0.088), PASAT score (R = −0.25, p = 0.014, pFDR = 0.039), SDMT score (R = −0.48, p = 0.0044, pFDR = 0.015), WMH volume (R = 0.29, p = 0.00020, pFDR = 0.00085) and choroid plexus volume (R = 0.36, p < 0.0001, pFDR < 0.0001) (Fig. 3d).

    Disability worsening and relapse of AQP4 + NMOSD and MS atrophy subtypes

    Here, we reported the step-wise backward Cox regression findings (final model by “autoReg” package in R, see Table 2 for details). In AQP4 + NMOSD, NMOSD-CE showed relatively reduced EDSS progression (Hazard Ratio [HR] = 0.11, 95%CI [0.01, 0.99], p = 0.049) and relapse (HR = 0.13 [0.03, 0.69], p = 0.017). In MS, a late stage had a slightly increased risk of disease phenotype conversion from relapsing–remitting MS to SPMS (HR = 1.03, [1.00, 1.06], p = 0.045). No association of disease subtypes, stages, age or sex was observed for the follow-up EDSS worsening or relapse of MS. A summary of AQP4 + NMOSD and MS atrophy subtypes were provided in Fig. 4.

    Table 2 Univariate and multivariate cox proportional-hazards regression for follow-up disability worsening and relapse in NMOSD and MS
    Fig. 4
    figure 4

    A theoretical model summarizing brain and spinal cord atrophy subtypes in AQP4 + NMOSD (a) and MS (b). Atrophy varies along the axis of disability, relapse, cognition decline, age and disease duration (vertical axis in the diagram) in different AQP4 + NMOSD and MS subtypes. Atrophy varies along a spatiotemporal dimension (horizontal axis in the diagram), such that an individual can be described by their fit along one of at least three trajectories. The text indicates the clinical characteristics of each subtype. The text in bold reflects major clinical differences between subtypes, while normal text reflects MR-related characteristics that differentiate subtypes from normal-appearing individuals. AQP4, aquaporin 4; NMOSD, neuromyelitis optica spectrum disorders; MS, multiple sclerosis; NMOSD-C, cortical atrophy leading subtype of AQP4 antibody positive (AQP4 +) NMOSD; NMOSD-SC, spinal cord atrophy leading subtype of AQP4 + NMOSD; NMOSD-CE, cerebellar atrophy leading subtype of AQP4 + NMOSD; MS-C, cortical atrophy leading subtype of MS; MS-SC, spinal cord atrophy subtype of MS; MS-DGM, deep gray matter atrophy subtype of MS; WM, white matter

    Treatment response to DMT among AQP4 + NMOSD and MS atrophy subtypes

    For response to DMT regarding relapse, in AQP4 + NMOSD (Fig. 5), response rates were 78.6% (11/14) for NMOSD-NA, 38.5% (10/26) for NMOSD-C, 27.3% (3/11) for NMOSD-SC and 60.0% (3/5) for NMOSD-CE. NMOSD-C (p = 0.015, pFDR = 0.046) and NMOSD-SC (p = 0.010, pFDR = 0.046) had lower response rates compared with NMOSD-NA. In MS, response rates were 78.6% (11/14) for MS-NA, 77.8% (14/18) for MS-C, 37.9% (11/29) for MS-SC and 42.9% (9/21) for MS-DGM. MS-SC had a lower response rate than MS-NA (p = 0.013, pFDR = 0.038) and MS-C (p = 0.0078, pFDR = 0.038). MS-DGM had a lower response rate compared with MS-NA (p = 0.037, pFDR = 0.055) and MS-C (p = 0.027, pFDR = 0.054).

    Fig. 5
    figure 5

    Treatment response to DMT regarding the disease relapse and physical disability worsening (EDSS worsening) among AQP4 + NMOSD and MS atrophy subtypes. AQP4, aquaporin 4; NMOSD, neuromyelitis optica spectrum disorders; MS, multiple sclerosis; NMOSD-NA, “normal-appearing” AQP4 antibody positive (AQP4 +) NMOSD; NMOSD-C, cortical atrophy leading subtype of AQP4 + NMOSD; NMOSD-SC, spinal cord atrophy leading subtype of AQP4 + NMOSD; NMOSD-CE, cerebellar atrophy leading subtype of AQP4 + NMOSD; MS-NA, “normal-appearing” MS; MS-C, cortical atrophy leading subtype of MS; MS-SC, spinal cord atrophy subtype of MS; MS-DGM, deep gray matter atrophy subtype of MS; DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale

    For response to DMT regarding EDSS worsening, in AQP4 + NMOSD (Fig. 5), response rates were 85.7% (12/14) for NMOSD-NA, 84.6% (22/26) for NMOSD-C, 54.5% (6/11) for NMOSD-SC and 100% (5/5) for NMOSD-CE. No statistical difference among AQP4 + NMOSD subtypes was observed. In MS, response rates were 85% (17/20) for MS-NA, 85.7% (18/21) for MS-C, 53.3% (32/60) for MS-SC and 73.3% (22/30) for MS-DGM. MS-SC had a lower response rate than MS-NA (p = 0.012, pFDR = 0.035) and MS-C (p = 0.0086, pFDR = 0.035).

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  • Pokémon Go Kanto Celebration Timed Research quest, research tasks and Collection Challenge

    Pokémon Go Kanto Celebration Timed Research quest, research tasks and Collection Challenge

    Kanto Celebration makes the original Gen 1 Pokémon the focus this week in Pokémon Go.

    There’s a rotating set of Kanto Celebration Timed Research quests throughout this Pokémon Go event, along with a Kanto Celebration Collection Challenge waiting to be conquered!

    Don’t forget to get out the Kanto Celebration research tasks and sizable bonuses list either. The XP Celebration quest is continuing throughout this event.

    On this page:

    ‘Kanto Celebration Near and Farfetch’d’ quest steps and rewards

    Kanto Celebration: Near and Farfetch’d is the first Timed Research quest running throughout this Pokémon Go event. It will be available until Wednesday 3rd September at 10am (local). Once this time passes you’ll no longer be able to collect its rewards and it will be replaced with the Kang You Dig It quest.

    So let’s take a look at the Kanto Celebration: Near and Farfetch’d Timed Research quest steps. Just be wary of spoilers!

    ‘Kanto Celebration: Near and Farfetch’d’ Step 1 of 1

    • Catch 50 Pokémon – 5000 XP
    • Use 10 Razz Berries to help catch Pokémon – 25 Mega Venusaur Energy
    • Use 10 Pinap Berries while catching Pokémon – 25 Mega Charizard Energy
    • Use 10 Nanab Berries while catching Pokémon – 25 Mega Blastoise Energy
    • Spin 5 PokéStops or Gyms – 10 Ultra Balls

    Rewards: 5000 XP, 5000 Stardust and a Farfetch’d encounter.

    First Partner Collection Challenge Pokémon list

    First Partner Collection Challenge is part of the Kanto Celebration event in Pokémon Go. This means you have until Sunday 7th September at 8pm (local time) to earn its rewards. (Remember to claim them after you’ve completed the Collection Challenge!)

    Keep in mind that six of Pokémon in this Collection Challenge can only be obtained through evolution and getting them through any other means, such as trading, will not count towards First Partner.

    Here’s all of the Pokémon in the First Partner Collection Challenge and how to get them:

    • Bulbasaur – In the wild or event-exclusive research task (Catch 5 Bulbasaur, Charmander or Squirtle)
    • Ivysaur – Evolve Bulbasaur using 25 Bulbasaur Candy
    • Venusaur – Evolve Ivysaur using 100 Bulbasaur Candy
    • Charmander – In the wild or event-exclusive research task (Catch 5 Bulbasaur, Charmander or Squirtle)
    • Charmeleon – Evolve Charmander using 25 Charmander Candy
    • Charizard – Evolve Charmeleon using 100 Charmander Candy
    • Squirtle – In the wild or event-exclusive research task (Catch 5 Bulbasaur, Charmander or Squirtle)
    • Wartortle – Evolve Squirtle using 25 Squirtle Candy
    • Blastoise – Evolve Wartortle using 100 Squirtle Candy

    Rewards: 100 Mega Venusaur Energy, 100 Mega Charizard Energy and 100 Mega Blastoise Candy.

    Kanto Celebration field research tasks

    Here are the Kanto Celebration field research tasks in Pokémon Go:

    • Catch 5 Bulbasaur, Charmander or Squirtle reward – Bulbasaur, Charmander or Squirtle encounter
    • Use 5 Berries to help catch Pokémon reward – 10 Poké Balls, five Great Balls or two Ultra Balls
    • Evolve a Pokémon reward – One Rare Candy
    • Mega Evolve a Venusaur, Charizard or Blastoise reward – 10,000 XP
    • Spin 5 PokéStops or Gyms reward – 10 Mega Venusaur, Charizard or Blastoise Energy



    August in Pokémon Go is coming to a close with the Sunkissed Shores event and the release of Dondozo! There also levelling changes coming soon.

    You can now catch Dynamax Pokémon through Max Battles. First, however, you need to visit Power Spots to collect Max Particles and complete the To the Max! quest.

    Don’t forget to try out Routes, Gift Exchange and Party Play while you’re hunting down rare Pokémon, fighting in the Go Battle League or competing in PokéStop Showcases.

    Kanto Celebration bonuses

    • Double XP from spinning PokéStops.
    • Mega Evolution duration tripled.
    • One guaranteed Candy XL from evolving Pokémon.
    • Surprise encounters from Go Snapshot!
    • Evolving an Ivysaur into Venusaur will teach it Frenzy Plant (Grass-type Charged Attack).
    • Evolving a Charmeleon into Charizard will teach it Blast Burn (Fire-type Charged Attack).
    • Evolving a Wartortle into Blastoise will teach it Hydro Cannon (Water-type Charged Attack).


    Kanto Celebration wild Pokémon encounters

    Here are the Pokémon appearing more frequently in the wild during Kanto Celebration:

    • Bulbasaur
    • Charmander
    • Squirtle
    • Weedle
    • Pidgey
    • Abra
    • Slowpoke
    • Gastly
    • Chansey
    • Magikarp
    • Snorlax

    Kanto Celebration pay-to-play quest

    • $4.99 or the equivalent pricing tier in your local currency.
    • Non-refundable and can not be purchased using PokéCoins.
    • Can gift to players you’re Great Friends or higher with.
    • Rewards include Dynamax Articuno, Dynamax Zapdos and Dynamax Moltres.

    Hope you enjoy the Kanto Celebration event!

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  • Alex Noren Named Final European Vice Captain for the 2025 Ryder Cup

    Alex Noren Named Final European Vice Captain for the 2025 Ryder Cup

    By Ryder Cup Europe On September 2, 2025 10:00 UTC

    Luke Donald has named Alex Noren as his fifth and final Vice Captain for the 2025 Ryder Cup which will be played at Bethpage Black, New York, USA from September 26-28, 2025.

    Noren was a key part of Team Europe’s 2018 victory at Le Golf National in Paris, France, securing two points from three matches – including a memorable 40-foot putt on the 18th green to defeat Bryson DeChambeau 1up in the final Sunday singles match, as Europe triumphed 17½-10½ over the United States.

    The 43 year old Swede joins brothers Francesco and Edoardo Molinari, Thomas Bjørn and José María Olazábal in Donald’s completed backroom team as Team Europe aims to retain the Ryder Cup in New York.

    Noren said: “It was a big shock when I found out. I didn’t expect it at all. I want to bring a good attitude to the team room. Bring some knowledge. I’ve been in this game a long time.

    “This Ryder Cup is going to be one of the toughest ones to win because of where it is. It’s going to be a very tough crowd, but I think that can feed our players as well.

    “All of us who are part of the team have played a lot in America, so we’re used to the fans, we’re used to the courses, the course setups.

    “We don’t get to be part of team events that often. We all know how much it means for everybody who’s part of it, and who has played on it and we’re looking forward to it.”

    Captain Donald said: “I’m really delighted to announce Alex Noren as our final Vice captain. Alex brings a lot to the table, he is obviously a Ryder Cup player himself, having played in 2018 in France, and he has played on both the DP World Tour and the PGA TOUR at very high level.

    “I am excited to have him on board with the team and he just couldn’t have been happier, more honoured, to take the role.

    “He will do everything that he can to help the team. He’s a humble guy, it’s never about Alex. It’s always about the team and I just think he has great characteristics, which will be vital for his role as a Vice Captain.

    “I love Alex’s demeanour, his work ethic, how he goes about things. He prepares as well as anyone when it comes to his golf. And you know that is important.

    “There’s a bond there with some of the Scandinavian players on our team, but he gets along so well with everyone. He is a good friend of mine, we practise together at the Bears Club where other players who are going to be on that team also practise. So he has a great familiarity with a lot of the guys and I think that’s really useful.

    “It’s full steam ahead now. I’m extremely excited to have everything in place, the last pieces of the puzzle. The team is set, the VCs are set, and we’re ready to go.”

    Outside the Ryder Cup arena, Alex Noren has claimed 11 DP World Tour titles, most recently at the Betfred British Masters last month, a tournament he won for the second time.

    Noren has also been a consistent and dependable presence for Team Europe in professional team competitions, contributing to multiple victories across different formats. He made his debut at the Royal Trophy in 2010, followed by appearances in the Seve Trophy (2011) and World Cup of Golf (2011, 2016), proudly representing Sweden on the global stage. He played a key role in Europe’s victory at the 2018 EurAsia Cup, setting the tone for a standout year in team golf.

    Later that season, Noren earned his place at the 2018 Ryder Cup in Paris – a career-defining moment. He contributed two points from three matches, teaming up with Sergio Garcia for a commanding 5&4 win over Phil Mickelson and DeChambeau in the Friday foursomes, before the pair lost 3&2 to Bubba Watson and Webb Simpson on Saturday. Noren then secured a memorable 1up victory over DeChambeau in the Sunday singles, helping seal Europe’s emphatic win.

    His most recent team appearance came at the 2023 Hero Cup, where he once again played a valuable role in Continental Europe’s victory.

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  • CDC Chops Foodborne Illness Surveillance – Medscape

    1. CDC Chops Foodborne Illness Surveillance  Medscape
    2. The CDC quietly scaled back a surveillance program for foodborne illnesses  NBC News
    3. CDC dramatically scales back program that tracks food poisoning infections  Daily Bulletin
    4. The CDC Is Scaling Back a Major Food Safety Program—What It Means for You  health.com
    5. CDC cuts back foodborne illness surveillance program  CIDRAP

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  • Pakistan vs Afghanistan Live Streaming in India: When & where to watch 4th T20I on TV & online? PAK vs AFG predicted XIs

    Pakistan vs Afghanistan Live Streaming in India: When & where to watch 4th T20I on TV & online? PAK vs AFG predicted XIs

    Having won the series opener against Afghanistan, Pakistan are aiming for a repeat when both teams meet for a second time in the ongoing T20I tri-series in Sharjah on Tuesday. With two wins from two matches, pakistan are on top of the points table with four points. Afghanistan, who had lost to Pakistan in their first game, came back to winning ways with a 38-run win over hosts United Arab Emirates (UAE) on Monday.

    If Salman Ali Agha was the lone batter to shine for Pakistan in their first match, the likes of Hasan Nawaz and Saim Ayub rose to the occasion against UAE. Having said that, Pakistan needs the likes of Sahibzada Farhan and Fakhar Zaman to contribute with the bat too.

    As far as the bowling is concerned, Haris Rauf dismantled Afghanistan with a four-wicket haul in the first game while Hasan Ali took three wickets in the second. Unlike in the first game, the Pakistan bowlers were guilty of conceding more that 150 runs against minnows UAE.

    On the other hand, Afghanistan would like Rahmanullah Gurbaz to fire at the top. In both the games, Gurbaz could only manage 45 runs. Although the likes of Sediqullah Atal and Ibrahim Zadran scored fifties against UAE, Afghanistan will be looking for their top three to fire together at the top of the batting order.

    Pakistan vs Afghanistan 4th T20I match details

    Venue: Sharjah Cricket Stadium, Sharjah

    Pakistan vs Afghanistan head-to-head in T20Is

    Pakistan have played Afghanistan in eight T20Is with the Men in Green emerging victorious five times. Three games were won by Afghanistan. The last time Pakistan beat Afghanistan was last month during the ongoing tri-series when they won by 39 runs.

    Pakistan vs Afghanistan 4th T20I probable XIs

    Pakistan: Sahibzada Farhan, Saim Ayub, Fakhar Zaman, Salman Agha (c), Hasan Nawaz, Mohammad Nawaz, Mohammad Haris (wk), Faheem Ashraf, Hasan Ali, Salman Mirza, Sufiyan Muqeem

    Afghanistan: Rahmanullah Gurbaz (wk), Ibrahim Zadran, Sediqullah Atal, Darwish Rasooli, Karim Janat, Azmatullah Omarzai, Rashid Khan (c), Mohammad Nabi, Sharafuddin Ashraf, Mujeeb Ur Rahman, Fazalhaq Farooqi

    How to watch PAK vs AFG 4th T20I in India?

    There is no official broadcaster for the T20I tri-series involving Pakistan, Afghanistan and UAE. Indian fans can still watch live streaming of Pakistan vs Afghanistan 4th T20I on FanCode app and website from 8:30 PM IST.

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  • 14 of the best films to watch this September

    14 of the best films to watch this September

    Twinless

    This ingenious and outrageous comedy drama was showered with rave reviews when it premiered at the Sundance Film Festival in January. But all of those reviews were careful not to give too much away, because the twists in Twinless are what make it so remarkable. The premise is that Roman (Dylan O’Brien) has an identical twin who dies in a car crash. Roman goes to a twin bereavement support group, where he meets Dennis (the film’s writer-director, James Sweeney), and the two become close friends. But “the initial premise is merely a small fraction of what this film has in store as it upends expectations and runs with them as far as it can”, said Chase Hutchinson in The Wrap. “It’s a juggling act of tones that manages to be funny, chaotic, dark and even unexpectedly poignant… what fun Sweeney has contorting his characters into a whole host of hilarious, yet still uncomfortable, situations.”

    Released on 5 September in the US and Canada

    Universal Studios (Credit: Universal Studios)Universal Studios

    Him

    There’s no sign yet of the next horror film directed by Jordan Peele (Get Out, Us, Nope), but in the meantime we have Him, which Peele produced, and which seems to have his signature blend of shocks, mystery and sly social commentary. It’s the twisted story of a rising American football star, Cameron Cade (Tyriq Withers), who needs some extra help to fulfil his potential. His hero is Isaiah White (Marlon Wayans), a legendary quarterback, so Cade is thrilled to be invited to White’s isolated training compound. Once he’s there, though, he discovers that the training involves gory violence and hallucinatory weirdness. But if that’s what it takes to be a sporting superstar, could the ordeal be worth it? Written by Zack Akers and Skip Bronkie, Him is a “mash-up where sports meet horror”, says its director, Justin Tipping. “I guarantee, this film does not play it safe.”

    Released on 19 September in the US and Canada and 25 September in Australia

    Vincent Productions (Credit: Vincent Productions)Vincent Productions

    Riefenstahl

    Leni Riefenstahl’s documentaries Triumph of the Will and Olympia are Nazi propaganda, though Riefenstahl argued that she cared only about art and beauty, not politics. She spent plenty of time with Hitler, and her claims that she was unaware of his crimes against humanity were never wholly convincing. Andres Veiel’s documentary goes further: it argues that Riefenstahl was a Nazi throughout her life, however much she protested otherwise. The film is an “extraordinary deep-dive documentary about the original cancelled artist”, said The Guardian. “Veiel gained unprecedented access to Riefenstahl’s personal archive and combed through film footage, audio, photos and writing… He paints a textured, complex portrait that feels close to definitive; a slice of dark history that speaks (eloquently, implicitly) to present-day tensions.”

    Released on 5 September in the US

    —

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  • We still haven’t documented 90 percent of animals on Earth

    We still haven’t documented 90 percent of animals on Earth

    It’s easy to assume, as many people do, that our planet is well explored. In the last few centuries, humans have summited Earth’s highest peaks, dived its deepest ocean trenches, and trekked to the North and South poles, documenting the diversity of life along the way — the many birds, butterflies, fish, and other creatures with which we share our big planet.

    Life on Earth is now largely known.

    The more that scientists study the planet’s biodiversity, the more they realize how little of it we know. They estimate that for every species we’ve discovered, there are likely at least another nine or so that remain undiscovered or unidentified, meaning around 90 percent of life on Earth is unknown.

    This doesn’t include the big stuff — the black bears and belugas and bald eagles, all of which have scientific names and descriptions published in academic journals. The unknown is made up of small organisms, such as insects, mites, and crustaceans. These species are the nuts and bolts of ecosystems: They produce soil, pollinate crops, and feed almost everything. And most of them have yet to be identified.

    In just one fly family known as Cecidomyiidae, for example, scientists estimate there could be as many as 1.8 million species globally, and yet fewer than 7,000 have been described. This is especially remarkable given that the total number of described species across the entire animal kingdom is somewhere around 2 million.

    Biologists describe animals like this as dark taxa, a term that refers to groups of organisms in which the bulk of species are undescribed or undiscovered. Some taxonomists have also called them biology’s dark matter.

    “Most people think that life on Earth is described, and we have a good idea of how ecosystems are functioning,” said Emily Hartop, a fly researcher and taxonomist at the Norwegian University of Science and Technology, who studies dark taxa. “The reality is that for most species on Earth, we don’t know what they are, we don’t know where they are, we don’t know what they’re doing. They are unknown.”

    Center for Biodiversity Genomics, University of Guelph

    Center for Biodiversity Genomics, University of Guelph

    Center for Biodiversity Genomics, University of Guelph

    Center for Biodiversity Genomics, University of Guelph

    Scientists who study dark taxa argue that lifting the shadow on these organisms is essential to our own survival. If we don’t know what constitutes our ecosystems, we risk killing off the key players that make them function — or failing to detect a potential threat, such as a disease-carrying insect that could set off the next global pandemic.

    “The little things run the planet,” said Rudolf Meier, a researcher at Berlin’s Museum of Natural History and Humboldt University of Berlin who also studies dark taxa.

    Hartop and some other researchers have dedicated their careers to exposing dark taxa — to making Earth’s unknown known. But filling these gaps is an enormous task and, until recently, considered impossible. The challenge comes down to process: How do you identify millions upon millions of species that are tiny, often look the same, and lack the traditional sort of charisma that funds expeditions?

    Dark taxa biologists find hundreds of new species wherever they look

    A little over a decade ago, when Hartop was living in Los Angeles, she and her colleagues set up bug traps in backyards across the city. They were mesh tents with openings, known as Malaise traps. Once flies buzz into them, they get stuck and navigate — rather unfortunately for them — into a vial of ethanol. The ethanol both kills and preserves the animals.

    New species of scuttle flies

    Over the course of just one year, the traps collected 99 species of scuttle flies, small insects in the family Phoridae that look, to my untrained eyes, a lot like fruit flies. Forty-three of those species were new to science and had never been described before.

    When scientists look for dark taxa, they seem to find new species everywhere. Meier and his colleagues recently collected fungus gnats in Singapore, and their traps revealed 120 species. All but four or five were unknown to science. When researchers went looking for wasps in Costa Rica that parasitize other insects, they found 416 species. More than 400 of them hadn’t been described yet.

    And the opportunity for discovery extends beyond the animal world. Scientists recently analyzed genetic codes from thousands of specimens of ectomycorrhizal fungi — a type of fungi that form symbiotic relationships with plant roots — and found that only around 20 percent of those codes matched known species.

    Why have these organisms been overlooked for so long? One reason is that they’re typically small, often measuring less than 5 millimeters, Meier said. That makes them harder to notice — and less exciting by traditional standards.

    “Funders are much more likely to give you money for birds and butterflies, because that’s something that a funder, who is not a biologist, finds much more relatable,” Meier told me. “If I want to get money for doing things on dark taxa, I first have to override these biases.”

    But a far bigger obstacle is that these groups of life are extremely diverse. There are three species of elephants and eight species of bear. Meanwhile, there could be 1 million species of scuttle flies globally, Hartop said.

    That creates a problem of scale. While trapping bugs in tents is easy, it’s much harder to identify them and demonstrate that they’re different from other species that have already been described. Until recently, it was nearly impossible.

    We are in the Golden Age of discovery

    For hundreds of years, scientists have largely categorized animals by their appearance. A toucan is obviously different from a robin, which is obviously different from a hummingbird. Scientists use these distinctions in form to separate animals by species, typically defined as organisms that reproduce with each other but not with other animal groups.

    The study of form, known as morphology, has been used to categorize small things, too, such as moths and butterflies. But for some animal groups — scuttle flies, mites, and nematodes, for example — this approach is inadequate. While distinguishing these animals by appearance is often possible, it typically requires an enormous amount of time and expertise; scientists literally have to look at them one by one through a microscope. Plus, looks can be deceiving: A bunch of, say, black-and-blue butterflies might appear identical but come from different genetic lineages that make them distinct species.

    A butterfly that’s both black and blue

    That’s why a technology called DNA sequencing has been such a game-changer. In the 1970s, scientists figured out how to sequence part of an organism’s DNA, producing a string of letters that corresponds to its genes. They later discovered that they could use just a small snippet of that sequence to tell one species apart from another. In 2003, a Canadian biologist named Paul Hebert dubbed those snippets “barcodes” because they serve as unique species IDs, akin to barcodes on cereal boxes in the grocery store.

    Over time, scientists sequenced animals and uploaded their barcodes to databases, helping organize and reorganize the animal kingdom. All the while, the technology evolved. DNA sequencing is now so advanced that taxonomists — those who classify life — can barcode thousands of specimens at one time.

    It’s this approach that’s helping illuminate dark taxa: Researchers can collect scores of specimens from the field, sequence portions of their DNA, and then upload those bits of code to an existing database to see if they match known species. If not, they might represent something new.

    Even with modern DNA sequencing, identifying unknown life is, to be clear, still very hard. A big issue is that there aren’t barcodes for most species that scientists have already described. Museums might have physical specimens — dead moths or beetles in a drawer in their basement — that lack genetic data in online databases. So just sequencing a discovery is usually not enough to prove that something is new to science.

    When scientists are confident that they’ve found something new, they’ll face additional challenges if they want to formally describe the animal and give it a scientific name. That typically requires multiple lines of evidence and a description published in a scientific journal. Doing that for dark taxa — which, again, have hundreds of thousands of unknown species — would be incredibly time-consuming. (The world of taxonomy is full of drama about the species-naming process and how much evidence scientists should be required to provide. There’s also a debate about whether formally naming species actually matters if they already have unique DNA sequences that identify them.)

    Nonetheless, modern DNA sequencing has massively sped up the process for discovering and identifying life. It’s pretty extraordinary: Even though we’ve known about the most visible species around us for hundreds of years, only now are we in the Golden Age of species discovery.

    “It’s unbelievable,” said Hebert, a professor at the University of Guelph in Ontario who oversees the Center for Biodiversity Genomics, a DNA-barcoding research center. “This is the age of bio-discovery.”

    Can we describe all life on Earth?

    That’s the goal. While there are no reliable estimates for the total number of species on Earth, it’s likely in the tens of millions. And again, only around 2 million are formally described, Hebert said.

    Before modern sequencing became a reality, identifying all life on Earth would have taken hundreds, if not thousands, of years and likely would have cost trillions of dollars. Now, some scientists are confident that they can do it in a matter of decades or even years.

    In 2005, Hebert launched a project with his colleague Sujeevan Ratnasingham that is essentially trying to collect DNA data for every animal on Earth. So far, the project — known as Barcode of Life — has sequences for roughly 1.5 million species, Hebert said, though many of those are not formally described. To barcode the rest would require no more than $1 billion, he told me confidently. That money would help fund expeditions and DNA sequencing around the world.

    “We want barcode records for every species,” Hebert said. “If I can persuade the world to support this with about $1 billion, which is trivial, we can complete the inventory of animal life by 2040 — I am certain.”

    Hebert and other taxonomists imagine a world in which all species are known and can thus be tracked. Just as we monitor the weather for looming disasters, complete inventories of animal life could allow scientists to monitor biodiversity — both the obvious and obscure stuff — to see how our ecosystems are changing and what that means for us. Are ocean food chains we rely on shrinking? Are the insect larvae that make our soils fertile in decline? Is a pathogen on the loose?

    But there’s also a more noble reason to discover life, he says. “This is the planet we live on,” Hebert said. “We really should understand the organisms that we share it with.”

    And if you’ve got a billion dollars lying around, you can apparently help.

    “For a billionaire, it’s a no-brainer,” Hebert said. “That’s a legacy for that person. You only get to do it once: discover life on our planet.”

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  • Pak Army chief Asim Munir meets China President Xi Jinping day after Modi’s SCO visit concludes | Latest News India

    Pak Army chief Asim Munir meets China President Xi Jinping day after Modi’s SCO visit concludes | Latest News India

    Pakistan Army chief Field Marshal Asim Munir formally met Chinese President Xi Jinping, as part of Prime Minister Shehbaz Sharif’s delegation, on Tuesday.

    Pakistan Army chief Field Marshal Asim Munir. (Reuters file)

    The meeting comes a day after a summit of the Shanghai Cooperation Organisation (SCO), at which India’s PM Narendra Modi was among the attendees, concluded with a joint declaration condemning the Pahalgam attack in particular, and terrorism in general.

    Pakistan was not expressly mentioned but PM Modi spoke of “some nations” using terror as policy. And the declaration was a big step forward from India’s perspective for Pahalgam to be mentioned directly, as the Modi government has blamed Pakistan for the attack in April. Indian forces carried out retaliatory strikes on terror bases as part of Operation Sindoor in May.

    Munir, who is considered the most powerful man in Pakistan, was promoted from General to Field Marshal soon after the operation as he claimed a successfully pushback.

    He was part of the Pakistan team that participated in the SCO summit in Tianjin and will attend a grand parade of the Chinese army to on Wednesday to mark the 80th anniversary of the Chinese win against the Japanese in World War 2.

    This is his second visit to China as army boss. In his first visit to China in July after taking over as Field Marshal, Munir met Vice President Han Zheng but not President Xi, unlike his predecessor General Qamar Javed Bajwa.

    Before that, Munir was hosted for lunch by US President Donald Trump, a rare gesture by an American leader which raised eyebrows in India as well as in China, considering Pak-China all-weather ties.

    While Xi met Prime Minister Narendra Modi and a host of other leaders, who attended the SCO summit in Tianjin, Sharif was allocated the slot on Tuesday to meet the Chinese President in Beijing. Munir was expected to join Sharif to watch the parade in which the Chinese military plans to display its most modern weapons.

    The weapons systems were of big interest to the Pakistan military as over 80 per cent of its weapons acquisitions are from China — a fact flagged by India after Op Sindoor.

    But there has been a realigment of relations by India with China, which were frosty for the past five years after the Galwan border clash, after Trump levied massive trade tariffs on India.

    Munir-Sharif and Xi held wide-ranging talks on bilateral & regional cooperation, said Pakistan’s deputy PM and foreign minister Ishaq Dar, who was also part of the team. Xi said the two sides should accelerate building an even closer China-Pakistan community and set up a model for the broader neighbourhood, according to Dar.

    China’s state-run Xinhua news agency quoted President Xi Jinping as saying that China stands ready to work with Pakistan to build upgraded versions of the China-Pakistan Economic Corridor and the China-Pakistan Free Trade Agreement. China hopes Pakistan will take effective measures to ensure the safety of Chinese personnel, projects and institutions in Pakistan, Xi further said, as per a PTI report.

    On his part, Sharif hailed the Global Governance Initiative (GGI), proposed by Xi at the SCO summit to improve global governance, saying it is of great significance for world peace, development and stability, and Pakistan will give it full support and work actively to implement it, added the report.

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  • Effect of epidural catheter design on analgesic efficacy during progra

    Effect of epidural catheter design on analgesic efficacy during progra

    Introduction

    Since programmed intermittent epidural bolus (PIEB) was introduced to maintain labor analgesia in 2006,1 it has been shown to provide a preferable analgesic effect with reduced consumption of local anesthetics, less motor block, fewer patient-controlled epidural analgesia (PCEA) boluses, and a lower incidence of instrumental vaginal deliveries. Additionally, PIEB improves maternal satisfaction compared to continuous epidural infusion (CEI) methods.2,3 Although many studies have explored variations in PIEB regimens (drug concentration, bolus dose, interval, bolus delivery rate) to optimize labor analgesia,4–6 less attention has been given to the specific design features of epidural catheters associated with this technique.7

    The effectiveness of epidural analgesia depends on several factors, including catheter design. Historically, the number of orifices in an epidural catheter has been linked to analgesic outcomes. Multi-orifice catheters have been reported to provide better analgesic efficacy than single-orifice catheters, given that the presence of multiple orifices can enhance drug distribution within the epidural space.8–11 However, these studies were conducted using conventional continuous infusion or manual bolus techniques. Our in vitro study12 revealed significant differences in flow and drug distribution between single- and multi-orifice catheters under varying rates of programmed intermittent bolus administration. Theoretically, anesthetic distribution within the epidural space is essential for adequate labor analgesia, especially when coverage of the lumbar epidural space (low thoracic and sacral dermatome coverage) is required. In a subsequent clinical trial,13 we found that single-orifice catheters outperformed multi-orifice catheters in terms of faster analgesic onset, lower local anesthetic consumption, and reduced PCEA use at a PIEB delivery rate of 480 mL/h. However, whether this effect persists at a commonly used rate of 360 mL/h remains unclear.

    This prospective, randomized, double-blind, controlled trial aimed to compare the analgesic outcomes of single-orifice and multi-orifice catheters at a 360-mL/h delivery rate during PIEB. We hypothesized that single-orifice catheters would improve labor analgesia and reduce ropivacaine consumption.

    Materials and Methods

    Study Population

    This prospective, randomized, double-blind study was approved by the Institutional Ethics Committee of Shanghai First Maternity and Infant Hospital (Ethics No: KS23161; March 20, 2023). This trial adhered to the Consolidated Standards of Reporting Trials (CONSORT) guidelines and was registered with the Chinese Clinical Trial Registry (No: ChiCTR2300072694; principal investigator: Weijia Du; date of registration: June 21, 2023; Chairperson of the ethics committee: Ye Lou) before patient enrolment.

    The inclusion criteria were as follows: healthy, term, nulliparous women, aged 20 to 40 years, with an American Society of Anesthesiologists physical status II; singleton pregnancies with vertex presentation; active labor with progressive cervical dilation; requesting epidural analgesia with cervical dilation between 2 and 5 cm; and a numerical rating scale (NRS) pain score >5 (NRS: 0 = no pain and 10 = worst pain imaginable). Exclusion criteria included a body mass index >40 kg/m, history of drug abuse, use of pharmacological analgesics within 4 h before the epidural request, contraindications to epidural anesthesia, conditions increasing the risk of caesarean delivery (ie, placenta previa, history of uterine anomalies or surgery), and fetal abnormalities. Eligible participants were given verbal and written information, and all provided written informed consent. Participants were excluded from further studies if delivery occurred within 1 h of epidural catheterization.

    Randomization and Concealment of Group Assignments

    Participants were randomly assigned in a 1:1 ratio using fixed blocks of four, without stratification factors, generated by one of the investigators using SAS 9.4 (SAS Institute, Cary, NC). They were allocated to receive either a single-orifice epidural catheter (Group A) or a multi-orifice catheter (Group B). To ensure allocation concealment, staff not involved in the study placed group assignments in opaque, sealed envelopes. The anesthesiologist responsible for catheter placement based on group assignment was not included in the study. All other study personnel, including the nurse conducting cervical examinations and pain assessment at the request for labor analgesia, the research nurse performing the follow-ups, and the participants, were blinded to group allocation.

    Epidural kits labelled for Group A contained a 19-G, single-orifice, open-end, wire-reinforced, polyurethane, and flexible catheter, whereas kits for Group B contained a 19-G, four-lateral-hole, wire-reinforced, polyurethane, and flexible catheter (Arrow International, Westmeath, Ireland). All components of the epidural kits were identical except for the epidural catheter. The two types of catheters were manufactured by the same company, with different hole layouts being the only difference.

    Treatment Protocol

    Epidural Catheter Placement

    Standard maternal and fetal monitoring was performed, including baseline maternal heart rate and non-invasive arterial blood pressure (BP) measurements. An intravenous catheter was inserted, and 500 mL of lactated Ringer’s solution was infused over 15 min during the epidural procedure. The attending anesthesiologist placed all catheters. Analgesia was initiated with the parturient in the right lateral decubitus position, targeting the L2–L3 interspace using pre-procedural spinal ultrasound assessment. After identifying the epidural space via the loss-of-resistance technique, a single- or multi-orifice epidural catheter was advanced 4 cm into the epidural space, with the needle bevel-oriented cephalad, and secured. The parturients were then placed in a supine position with left uterine displacement. After confirming negative aspiration for blood and cerebrospinal fluid, a 3-mL test dose of 1.5% lidocaine with 15 μg of epinephrine was administered. Parturients with a positive test dose were withdrawn from the analysis. These cases were managed according to standard clinical practice: the epidural catheter was either repositioned or replaced, and alternative analgesia was provided as needed. Complications such as intravascular or intrathecal placement, paresthesia, or difficulty threading the catheter were recorded.

    Initiation of Labor Analgesia

    Epidural analgesia was initiated with a loading bolus of 12 mL of 0.1% ropivacaine mixed with sufentanil (0.3 µg/mL). This was administered 3 min after administering the test dose, delivered in 6-mL increments every 2 min. Adequate analgesia was defined as an NRS score ≤ 2 during two consecutive uterine contractions with no request for additional analgesia, confirmed by tocodynamometer tracings.

    Maintenance of Labor Analgesia

    After adequate analgesia was established, an epidural pump (Apon ZZB-IV; Jiangsu Apon Medical Technology, Jiangsu, China) was initiated to deliver PIEBs of 10 mL every 45 min, the first bolus was administered 45 min after the loading bolus. Additionally, all parturients had access to PCEA, which allowed 8-mL boluses with a 10-min lockout interval between PCEA or PIEB/PCEA boluses. The solution used for PIEB and PCEA was 0.1% ropivacaine with sufentanil (0.3 µg/mL). The injectate rate was set at 360 mL/h, with a 40-mL hourly maximum volume.

    Pain scores were recorded using NRS, and sensory blockade (assessed via cold stimulation) and motor strength were assessed every 2 min during the first 20 min, and subsequently at 30 min, 60 min, and then at 60-min intervals until delivery. Motor strength was measured using the modified Bromage score: 0= No impairment; 1= Inability to raise the extended leg but preserved knee and foot movement; 2= Inability to raise the extended leg or flex the knees, with retained foot movement; 3= Complete block (no movement at ankles, feet, or knees). Motor blockade was defined as a modified Bromage score ≥1. The sensory blockade level to cold was assessed bilaterally along the mid-clavicular line, from the caudal to the cephalad. The upper sensory block level was recorded as the highest dermatome, where the parturient no longer felt normal sensations compared to the forehead or cheek. Dermatomal levels in the lower extremities were tested at the inguinal crease at the midclavicular line (L1), anteromedial thigh (L2), medial femoral condyle above the knee (L3), medial malleolus (L4), dorsum web between the great and second toes (L5), lateral calcaneus (S1), and midpoint of the popliteal fossa (S2). The study continued for 6 h post-initial dose or until full cervical dilation, whichever occurred first.

    Standard care at the institution included non-invasive BP monitoring every 2 min during the first 20 min, then at 30- and 60-min intervals until delivery, along with continuous maternal heart rate, pulse oximetry, and fetal heart rate monitoring. Maternal hypotension episodes (systolic BP <90 mmHg or <80% of baseline) and fetal bradycardia (<110 bpm for >10 min) were recorded and treated properly. The parturient was excluded from the analysis if delivery occurred within 1 h of epidural catheterization. Data on analgesic usage were extracted from the investigator’s history of pump use after delivery.

    Inadequate Analgesia

    In the event of an NRS score >3 or a maternal request for additional medication 20 min after the loading bolus, the parturient was instructed to self-administer the PCEA bolus. If the pain persisted after two PCEA boluses within 20 min, a provider bolus of 5 mL of 0.2% ropivacaine was administered manually. If necessary, an additional 5 mL was administered after a 10-min interval. If adequate analgesia was still not achieved, the epidural catheter was replaced, and the parturient was withdrawn from the analysis.

    Outcomes

    The primary outcome was ropivacaine consumption per hour, calculated as the total amount of ropivacaine administered (via pump and provider-administered boluses) divided by the duration of labor analgesia (mg/h). The duration of labor analgesia was defined as the time from pump initiation to delivery. Secondary outcomes included the percentage of parturients with adequate analgesia 20 min after the initial epidural bolus, time to achieve adequate analgesia, PCEA boluses requested and delivered, time to first PCEA bolus request, and the number of clinician-administered boluses. Other analgesic characteristics such as the frequency of motor block and unilateral blockade were also collected.

    Additional data collected included demographic information, obstetric variables, maternal satisfaction (assessed 24 h after delivery using a 5-point rating scale: 5 = excellent, 4 = very good, 3 = good, 2 = fair, 1 = poor), and the incidence of side effects such as pruritus, vomiting, postpartum headache, hypotension, and fetal bradycardia.

    Statistical Analysis

    The primary outcome was ropivacaine consumption per hour. Data from a previous study13 involving 182 parturients indicated that the mean (standard deviation) ropivacaine used per hour was 14.45 mg (1.87 mg) with a single-orifice catheter and 15.49 mg (2.10 mg) with a multi-orifice catheter. A sample size of 59 participants per group provided 80% power to detect this difference at α = 0.05 using a two-sided t-test. To account for 5% dropouts and catheter failures, we aimed to enroll 124 participants. Sample size calculations were performed using PASS software (NCSS, Kaysville, UT).

    Data from this randomized controlled trial were analyzed on an intention-to-treat basis using SPSS (version 24.0; IBM, Armonk, NY). The normality of continuous data was tested using the Shapiro–Wilk test. Normally distributed data are presented as mean ± standard deviation and analyzed among groups using the t-test. Skewed data are presented as median [interquartile range] and compared using the Mann–Whitney U-test. Categorical variables are reported as frequencies (percentages) and were compared using the chi-squared (χ2) test. Standardized differences and 95% confidence intervals (CIs) were calculated for interval data using Hedge’s g and for ordinal and dichotomous data using Cliff’s delta, calculated via the “effsize” function in R software (version 4.1.2; R Foundation for Statistical Computing, Vienna, Austria) through R Studio (version 2023.06.1+524; RStudio, Boston, MA).

    To assess the within-subject variability in VAS scores between groups, a mixed-effects model with repeated measures was used, incorporating group, time, and their interaction as fixed effects, with a random intercept and group-specific residual variances. This was compared to a restricted model with equal residual variances. Maximum likelihood estimation was used to determine covariance parameters. The least squares mean for VAS scores was also estimated using mixed effects with repeated measures. Statistical analyses for the mixed-effects model were conducted using SAS (version 9.4; SAS Institute). P<0.05 was considered statistically significant.

    Results

    This study was conducted at Shanghai First Maternity and Infant Hospital between July 2023 and September 2023. The participant flow is outlined in Figure 1. A total of 102 participants were included in the final analysis (50 in the single-orifice catheter group and 52 in the multi-orifice catheter group). Maternal demographics and baseline characteristics were well-balanced between the two groups (Table 1).

    Table 1 Baseline Characteristics

    Figure 1 Flow chart showing study participant recruitment.

    The primary and secondary outcomes are summarized in Table 2. The median (interquartile range) ropivacaine consumption per hour showed no significant difference between the groups: 12.6 mg/h [11.6–13.2 mg/h] for the single-orifice catheter group and 12.8 mg/h [12.3–13.3 mg/h] for the multi-orifice catheter group (difference 29%; 95% CI, –10.2 to 68.2%; P=0.241, Figure 2). There were also no significant differences in the median time to the first PCEA bolus, the percentage of parturients who required PCEA, or the number of PCEA boluses administered between the two groups. However, a higher percentage of parturients achieved adequate analgesia 20 min after the loading bolus with the single-orifice catheter compared to the multi-orifice catheter (84.0% vs 63.5%, difference 22.5%; 95% CI, 9.2% to 35.1%, P=0.019). The median time to adequate analgesia was significantly shorter for the single-orifice catheter group at 8 min [4–16] compared to 15 min [9.5–22.5] for the multi-orifice catheter group (P=0.002). Pain scores were similar between the groups, except at 6 and 18 min (Table 3). None of the parturients in either group experienced motor or unilateral block. Maternal satisfaction scores were comparable between the groups, and there were no significant differences in side effects or catheter-related complications.

    Table 2 Analgesic Outcomes

    Table 3 Comparison of NRS Pain Scores at Each Time-Point. Values are Median (IQR [Range])

    Figure 2 Kaplan-Meier curves for time to achieving NRS ≤ 3 following initial bolus dosing with single-orifice or multi-orifice catheters. Survival probability indicates probability of subjects surviving with NRS ≤ 3 at given time.

    The obstetric and neonatal outcomes were also well-balanced between the two groups (Table 4).

    Table 4 Obstetric and Neonatal Outcomes

    Discussion

    In this randomized, double-blind, controlled study, no significant difference was found in hourly ropivacaine consumption between single- and multi-orifice wire-reinforced flexible catheters during the maintenance of labor analgesia with a PIEB at a delivery rate of 360 mL/h. Additionally, PCEA boluses requested and delivered, time to first PCEA bolus request, and the number of clinician-administered boluses were similar across both groups, suggesting that catheter design did not affect the quality of analgesia during labor maintenance. However, a higher percentage of parturients with NRS score ≤2 within 20 min of the loading bolus was observed in the single-orifice catheter group compared to the multi-orifice group.

    Several factors, such as patient position, the volume and concentration of the local anesthetic, the injection site, and epidural space compliance, can influence drug distribution in the epidural space. The limited available data make it difficult to determine whether the number and position of the catheter orifices impact analgesic outcomes and potential side effects. It has been suggested that multi-orifice catheters might allow for preferential efflux through single or multiple orifices depending on the rate and pressure of delivery.14 This could lead to greater lateral drug spread, improved injectate distribution,9 and better analgesic outcomes. However, under PIEB administration, flow dynamics at the catheter orifice may differ. In an in vitro study,12 we found that multi-orifice catheters offered no advantage over single-orifice catheters in drug spread when programmed injections were delivered at a rate above 360 mL/h. When combined with high-rate epidural injection, the open-ended design of single-orifice catheters may facilitate more efficient passage into the epidural space, leading to more extensive medication distribution. This has been linked to improved clinical outcomes under PIEB, such as improved analgesia and lower bupivacaine consumption.1–15 Our subsequent clinical findings supported this hypothesis,13 showing that single-orifice catheters resulted in a more rapid analgesic onset, reduced ropivacaine consumption, and better pain control at full cervical dilation compared to multi-orifice catheters at a PIEB delivery rate of 480 mL/h. However, in the present study with a programmed bolus rate of 360 mL/h, we did not observe any clinical benefits during the maintenance of labor analgesia. This could be attributed to the lower injection pressure at this delivery rate, which might be insufficient to produce a “jet effect” necessary for optimal drug dispersion through the open end of the epidural catheter. Bolus delivery rates are programmable and have varied significantly in previous studies. In vitro studies12–14,16 have demonstrated that an increasing delivery rate is associated with a higher delivery pressure at the catheter orifice. Multi-orifice catheters can generate higher pressures with higher delivery rates, sometimes triggering occlusion alarms.12–17 Therefore, single-orifice catheters may be preferable to multi-orifice catheters when considering the use of high-rate (>360 mL/h) PIEB administration for the maintenance of labor analgesia.

    This is the second randomized controlled trial investigating the analgesic efficacy of two different epidural catheters under a PIEB regimen. In this study, single-orifice catheters were associated with a higher percentage of parturients achieving adequate analgesia after the initial manual rapid bolus. They attained adequate analgesia almost in half the time as the multi-orifice catheters. A similar association was observed in our previous study,13 where an initial bolus was administered using a pump at a rate of 480 mL/h. These findings may hold clinical significance, suggesting that single-orifice catheters provide “transient” benefits regarding the faster analgesic onset when compared with multi-orifice catheters. Further studies are needed to explore the outcomes of these two catheter types in various clinical scenarios requiring manual epidural top-ups, such as epidural anesthesia for caesarean delivery, conversion from labor analgesia to anesthesia, and the management of breakthrough pain during labor.

    We observed no differences between the two groups in the incidence of difficult catheter insertion, paresthesia, intravascular cannulation, intrathecal placement, or challenging catheter removal. The materials used in manufacturing epidural catheters can influence clinical performance, including intravascular cannulation, paresthesia, and ease of catheter removal and placement.7 Early studies suggested that single-orifice catheters were associated with difficult placement11 and inadequate blocks.8–10 However, advancements in materials and the development of flexible inner wire coils in recent decades have significantly reduced the incidence of catheter-related complications and improved the quality of labor analgesia. Spiegel et al18 conducted a prospective, randomized, controlled trial and found no statistically significant differences in analgesic outcomes or complications between single-orifice, wire-reinforced polyurethane catheters and multi-orifice, wire-reinforced nylon catheters. The authors posited that the flexibility provided by the wire coil could mitigate the potential risks associated with single-orifice designs.

    The strength of our study is its randomized, double-blind design, which effectively minimized the bias and influence of known and unknown confounders. However, this study had some limitations. First, the study subjects were restricted to nulliparous parturients to obtain longer durations of labor analgesia. As a result, these findings may not be applicable to multiparous parturients with short labor durations. Second, the initiation of labor analgesia was achieved via conventional epidural analgesia in the current study, and the results may differ if using combined spinal-epidural or dural puncture epidural techniques. Both techniques are hypothesized to enhance drug transfer from the epidural to the intrathecal space, thereby hastening block onset and analgesic efficacy.19 Finally, the catheters used were from a single manufacturer. In terms of catheter design, including the number and position of orifices, there is a wide range of variability in the characteristics between single- and multi-orifice catheters from various brands, which could influence the distribution of epidural medication and catheter-related complications. Therefore, the results of the current study cannot be generalized to other brands of epidural catheters.

    Conclusion

    In conclusion, our study found no significant differences in analgesic quality between catheter designs during the maintenance of labor analgesia, as measured by hourly ropivacaine consumption and PCEA requests at a delivery rate of 360 mL/h under PIEB. However, the single-orifice catheter was associated with a more rapid analgesic onset after the loading bolus, suggesting that single-orifice catheters may be preferable for PIEB at higher delivery rates (>360 mL/h) compared to multi-orifice catheters.

    Data Sharing Statement

    • Intent to Share: We intend to share individual deidentified participant data collected during this clinical trial.

    • Specific Data to be Shared: This will include the raw deidentified dataset, the study protocol, the statistical analysis plan, and the informed consent form.

    • Access Method: The data will be made accessible to researchers who provide a methodologically sound proposal. Requests should be directed to the corresponding author, Weijia Du, at Email: [email protected].

    • Timeline: The data will become available 6 months after article publication and will remain accessible for a period of 5 years.

    Declaration of Helsinki Compliance

    This study was performed in line with the principles of the Declaration of Helsinki.

    Disclosure

    The authors report no conflicts of interest in this work. This manuscript was funded by National Science Foundation of China (NO. 82371533), the Science and Technology Commission of Shanghai Municipality (NO. 22XD1402400) and Shanghai Municipal Health Commission (20224Y0201.

    References

    1. Wong CA, Ratliff JT, Sullivan JT, et al. A randomized comparison of programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth Analg. 2006;102(3):904–909. doi:10.1213/01.ane.0000197778.57615.1a

    2. Sng BL, Zeng Y, de Souza NNA, et al. Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour. Cochrane Database Syst Rev. 2018;5:CD011344.

    3. Hussain N, Lagnese CM, Hayes B, et al. Comparative analgesic efficacy and safety of intermittent local anaesthetic epidural bolus for labour: a systematic review and meta-analysis. Br J Anaesth. 2020;125(4):560–579. doi:10.1016/j.bja.2020.05.060

    4. Howle R, Ragbourne S, Zolger D, et al. Influence of different volumes and frequency of programmed intermittent epidural bolus in labor on maternal and neonatal outcomes: a systematic review and network meta-analysis. J Clin Anesth. 2024;93:111364. doi:10.1016/j.jclinane.2023.111364

    5. Munro A, George RB, Andreou P. An innovative approach to determine programmed intermittent epidural bolus pump settings for labor analgesia: a randomized controlled trial. Anesth Analg. 2024;139(3):545–554. doi:10.1213/ANE.0000000000006813

    6. Lange EMS, Wong CA, Fitzgerald PC, et al. Effect of epidural infusion bolus delivery rate on the duration of labor analgesia: a randomized clinical trial. Anesthesiology. 2018;128(4):745–753. doi:10.1097/ALN.0000000000002089

    7. Toledano RD, Tsen LC. Epidural catheter design: history, innovations, and clinical implications. Anesthesiology. 2014;121(1):9–17. doi:10.1097/ALN.0000000000000239

    8. D’Angelo R, Foss ML, Livesay CH. A comparison of multiport and uniport epidural catheters in laboring patients. Anesth Analg. 1997;84(6):1276–1279. doi:10.1213/00000539-199706000-00019

    9. Segal S, Eappen S, Datta S. Superiority of multi-orifice over single-orifice epidural catheters for labor analgesia and cesarean delivery. J Clin Anesth. 1997;9(2):109–112. doi:10.1016/S0952-8180(97)00232-8

    10. Collier CB, Gatt SP. Epidural catheters for obstetrics. Terminal hole or lateral eyes?. Reg Anesth. 1994;19(6):378–385.

    11. Michael S, Richmond MN, Birks RJ. A comparison between open-end (single hole) and closed-end (three lateral holes) epidural catheters. Complications and quality of sensory blockade. Anaesthesia. 1989;44(7):578–580. doi:10.1111/j.1365-2044.1989.tb11446.x

    12. Du W, Song Y, Zhao Q, et al. The effect of open-end versus closed-end epidural catheter design on injection pressure and dye diffusion under various programmed intermittent epidural delivery rates: an in vitro study. Int J Obstet Anesth. 2022;51:103252. doi:10.1016/j.ijoa.2022.103252

    13. Yi J, Li Y, Yuan Y, et al. Comparison of labor analgesia efficacy between single-orifice and multiorifice wire-reinforced catheters during programmed intermittent epidural boluses: a randomized controlled clinical trial. Reg Anesth Pain Med. 2023;48(2):61–66. doi:10.1136/rapm-2022-103723

    14. Fegley AJ, Lerman J, Wissler R. Epidural multiorifice catheters function as single-orifice catheters: an in vitro study. Anesth Analg. 2008;107(3):1079–1081. doi:10.1213/ane.0b013e31817f1fc2

    15. Capogna G, Camorcia M, Stirparo S, et al. Programmed intermittent epidural bolus versus continuous epidural infusion for labor analgesia: the effects on maternal motor function and labor outcome. A randomized double-blind study in nulliparous women. Anesth Analg. 2011;113(4):826–831. doi:10.1213/ANE.0b013e31822827b8

    16. Klumpner TT, Lange EM, Ahmed HS, et al. An in vitro evaluation of the pressure generated during programmed intermittent epidural bolus injection at varying infusion delivery speeds. J Clin Anesth. 2016;34:632–637. doi:10.1016/j.jclinane.2016.06.017

    17. Krawczyk P, Piwowar P, Salapa K, et al. Do epidural catheter size and flow rate affect bolus injection pressure in different programmed intermittent epidural bolus regimens? An in vitro study. Anesth Analg. 2019;129(6):1587–1594. doi:10.1213/ANE.0000000000003650

    18. Spiegel JE, Vasudevan A, Li Y, et al. A randomized prospective study comparing two flexible epidural catheters for labour analgesia. Br J Anaesth. 2009;103(3):400–405. doi:10.1093/bja/aep174

    19. Heesen M, Rijs K, Rossaint R, et al. Dural puncture epidural versus conventional epidural block for labor analgesia: a systematic review of randomized controlled trials. Int J Obstet Anesth. 2019;40:24–31. doi:10.1016/j.ijoa.2019.05.007

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  • Every Brentford player on international duty in September | Brentford FC

    Every Brentford player on international duty in September | Brentford FC

    18 Brentford players are set to represent their nations during September.

    Jordan Henderson could become the second Bees player, behind Ivan Toney, to get a senior England Cap while Mikkel Damsgaard’s Denmark will host Aaron Hickey’s Scotland as qualifying for FIFA World Cup 2026 gets underway.

    Here are all the players on international duty (kick-off times shown in BST).

    Jordan Henderson – England

    FIFA World Cup 2026 Qualifiers

    Andorra (H) – Saturday 6 September, 5pm

    Serbia (A) – Tuesday 9 September, 7.45pm

    Nathan Collins and Caoimhín Kelleher – Republic of Ireland

    FIFA World Cup 2026 Qualifiers

    Hungary (H) – Saturday 6 September, 7.45pm

    Armenia (A) – Tuesday 9 September, 5pm

    Aaron Hickey – Scotland

    FIFA World Cup 2026 Qualifiers

    Denmark (A) – Friday 5 September, 7.45pm

    Belarus (A) – Monday 8 September, 7.45pm

    Mikkel Damsgaard – Denmark

    FIFA World Cup 2026 Qualifiers

    Scotland (H) – Friday 5 September, 7.45pm

    Greece (A) – Monday 8 September, 7.45pm

    Yehor Yarmoliuk – Ukraine

    FIFA World Cup 2026 Qualifiers

    France (H) – Friday 5 September, 7.45pm

    Azerbaijan (A) – Tuesday 9 September, 5pm

    Hákon Valdimarsson – Iceland

    FIFA World Cup 2026 Qualifiers

    Azerbaijan (H) – Friday 5 September, 7.45pm

    France (A) – Tuesday 9 September, 7.45pm

    Kristoffer Ajer – Norway

    International friendly and FIFA World Cup 2026 Qualifier

    Finland (H) – Thursday 4 September, 5pm

    Moldova (H) – Tuesday 9 September, 7.45pm

    Dango Ouattara – Burkina Faso

    FIFA World Cup 2026 Qualifiers

    Djibouti (A) – Friday 5 September, 5pm

    Egypt (H) – Tuesday 9 September, 5pm

    Benjamin Fredrick and Frank Onyeka – Nigeria

    FIFA World Cup 2026 Qualifiers

    Rwanda (H) – Saturday 6 September, 5pm

    South Africa (A) – Tuesday 9 September, 5pm

    Ethan Pinnock – Jamaica

    FIFA World Cup 2026 Qualifiers

    Bermuda (A) – Friday 5 September, 11pm

    Trinidad and Tobago (H) – Wednesday 10 September, 1am

    Ji-soo Kim – South Korea Under-22s

    2026 AFC Under-23 Asian Cup Qualifiers

    Macau (N) – Wednesday 3 September, 9.30am

    Laos (N) – Saturday 6 September, 9.30am

    Indonesia (N) – Tuesday 9 September, 1.30pm

    Michael Kayode – Italy Under-21s

    UEFA European Under-21 Championship Qualifiers

    Montenegro (H) – Friday 5 September, 5.15pm

    North Macedonia (A) – Tuesday 9 September, 5.15pm

    Antoni Milambo – Netherlands Under-21s

    UEFA European Under-21 Championship Qualifier

    Israel (H) – Tuesday 9 September, 4pm

    Yunus Emre Konak – Turkey Under-21s

    UEFA European Under-21 Championship Qualifier

    Croatia (H) – Tuesday 9 September, 6pm

    Jayden Meghoma – England Under-20

    International friendly

    Italy (H) – Friday 5 September, 7.30pm

    Julian Eyestone – USA Under-20

    International friendlies

    Morocco (N) – Friday 5 September, 6pm

    Morocco (N) – Sunday 7 September, 6pm

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