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  • Intranasal Esketamine Premedication Reduces Sevoflurane Requirements d

    Intranasal Esketamine Premedication Reduces Sevoflurane Requirements d

    Introduction

    Pediatric anesthesia management requires balancing adequate anesthetic depth with minimal side effects. Sevoflurane remains the preferred inhalational agent in pediatric practice due to its favorable induction characteristics and low airway irritation potential. However, it may produce excitatory phenomena during the induction and emergence phases, particularly in younger children.1 The laryngeal mask airway (LMA) has become integral to pediatric anesthesia, facilitating spontaneous ventilation during general anesthesia for minor surgical procedures.2 When insufficient anesthetic depth, LMA insertion can trigger significant protective airway reflexes, including laryngospasm and coughing.3 While deepening anesthesia effectively prevents these airway responses, higher sevoflurane concentrations have been associated with adverse neurological effects in susceptible patients, including epileptiform activity and emergence agitation, though individual patient factors significantly influence risk.4–6 Successful LMA placement therefore requires careful optimization of anesthetic depth, quantified as the minimum alveolar concentration required for LMA insertion (MACLMA).

    Premedication offers several advantages in pediatric anesthesia, including anxiety reduction, improved induction cooperation, enhanced anesthetic potentiation, and decreased anesthetic requirements.7,8 Studies have shown that midazolam and dexmedetomidine effectively reduce sevoflurane requirements for LMA insertion.9,10 However, these agents present significant limitations: delayed onset, prolonged recovery times, and potential for paradoxical agitation or hemodynamic instability.

    Esketamine, the S (+) enantiomer of ketamine, has emerged as a promising alternative for pediatric premedication.11 This N-methyl-D-aspartate receptor (NMDA) antagonist exhibits approximately twice the analgesic potency of racemic ketamine with fewer psychological side effects, minimal secretions, rapid onset, and shorter recovery time.12 Unlike conventional agents, esketamine preserves airway reflexes without causing cardiovascular depression. Intranasal administration is particularly suitable for pediatric patients as it avoids injection-related distress while ensuring efficient mucosal absorption.13

    Despite these advantages, the effect of intranasal esketamine premedication on sevoflurane requirements for LMA insertion in pediatric patients has not been investigated. This randomized controlled trial, therefore, examines whether intranasal esketamine at doses of 0.5 mg/kg and 1.0 mg/kg reduces the minimum alveolar concentration of sevoflurane required for LMA insertion in children undergoing elective strabismus surgery. We hypothesize that intranasal esketamine premedication will produce dose-dependent reductions in sevoflurane requirements, enabling adequate anesthetic depth at lower sevoflurane concentrations, thereby reducing risks associated with inadequate anesthesia and excessive volatile exposure.

    Methods

    Study Design and Participants

    This randomized, double-blind, placebo-controlled trial was conducted at Fujian Provincial Hospital, China, from November 2023 through September 2024. The Institutional Review Board approved the study protocol (approval number K2023-01-003) on January 18, 2023, with trial registration at the Chinese Clinical Trials Registry (https://www.chictr.org.cn/showproj.html?proj=208297, ChiCTR2300076364) on October 7, 2023. Written informed consent was obtained from all parents or legal guardians before enrollment. The study adhered to the Declaration of Helsinki principles, Good Clinical Practice guidelines, and CONSORT 2025 reporting standards.14

    We enrolled healthy children aged 2–5 years, classified as American Society of Anesthesiologists, with physical status I or II and scheduled for elective strabismus surgery, who were eligible for participation. We excluded patients with suspected difficult airway, recent respiratory conditions (within two weeks), recent sedative or analgesic use (within 48 hours), neuropsychiatric disorders, obesity (body mass index > 30 kg/m²), known allergies to study medications, or significant life events within one month of surgery (parental divorce, bereavement, relocation, or school changes) that might affect behavioral assessments.

    Randomization and Allocation Concealment

    Participants were randomly assigned in equal proportions (1:1:1) to one of three treatment groups using computer-generated randomization: control (saline), esketamine 0.5 mg/kg, or esketamine 1.0 mg/kg. Allocation concealment was ensured using sequentially numbered, opaque, sealed envelopes. An independent research pharmacist, isolated from the clinical team, prepared identical syringes labeled only with study codes on the day of surgery. This double-blind design was maintained throughout the trial, with parents/guardians, healthcare providers, and outcome assessors all blinded to treatment assignments.

    Premedication Protocol

    All premedications were administered in a designated preoperative area with parents present to reduce anxiety. Twenty minutes before anesthetic induction, participants received one of three intranasal treatments according to their randomization: 0.9% saline solution (control), esketamine 0.5 mg/kg, or esketamine 1.0 mg/kg. Each formulation was delivered at a standardized volume of 0.04 mL/kg using a 1-mL syringe. An independent nurse administered the medication by instilling equal volumes into each nostril while the child remained supine.

    Anesthetic Management

    Children followed standard fasting guidelines (6–8 hours for solids, 2 hours for clear liquids) before anesthesia.15 Standard monitoring was established on arrival in the operating room, including pulse oximetry, electrocardiography, capnography, and noninvasive blood pressure measurement. We used a face mask with a semi-closed circuit system for anesthesia induction, delivering 5% sevoflurane in oxygen at 6 L/min. Ventilation progressed from initial spontaneous breathing to gentle manual assistance, maintaining end-tidal carbon dioxide between 35–45 mmHg throughout the procedure. We maintained the core temperature at 36.8 ± 0.4°C using a forced-air warming system (Bair Hugger 755; 3M Healthcare, USA). Sevoflurane concentration and end-tidal carbon dioxide were continuously monitored using a CARESCAPE Monitor B650 (GE Healthcare, USA).

    Sevoflurane MACLMA Determination

    We determined the minimum alveolar concentration of sevoflurane required for LMA insertion using Dixon’s sequential up-and-down method.16 Starting concentrations followed established protocols: 2.0% for the control group based on published data for unpremedicated children.10 The esketamine groups began at lower concentrations (1.6% for 0.5 mg/kg and 1.2% for 1.0 mg/kg) reflecting the expected dose-dependent anesthetic-sparing effect of NMDA receptor antagonists. All concentrations were equilibrated for 15 minutes before LMA insertion to ensure steady-state conditions.

    To ensure unbiased assessment, a single experienced pediatric anesthesiologist (with over 200 LMA insertions annually) performed all procedures while blinded to the premedication type and sevoflurane concentration. Following each insertion attempt, the sevoflurane concentration was adjusted by ± 0.2% for the next patient in that group. An unsuccessful insertion (intentional movement, coughing, or airway reaction within one minute of insertion) led to a 0.2% increase, while a successful insertion prompted a 0.2% decrease. Independent observers, also blinded to treatment allocation, documented all responses to maintain assessment objectivity.

    Anesthesia and Recovery Protocol

    Following LMA placement assessment, anesthesia was deepened with 2.0 mg/kg propofol, 0.2 μg/kg sufentanil, and 0.3 mg/kg rocuronium. Maintenance anesthesia consisted of 2% sevoflurane in a 50% oxygen-air mixture. Analgesia included 1 mg/kg intravenous flurbiprofen axetil and 0.4% oxybuprocaine eye drops administered perioperatively. Antiemetic prophylaxis comprised 0.15 mg/kg dexamethasone and 0.1 mg/kg ondansetron. Following surgery and LMA removal, children were transferred to the PACU, where parents provided emotional support during recovery.

    Outcome Measures

    The primary outcome was the MACLMA of sevoflurane, determined using Dixon’s up-and-down sequential allocation method.17 This method relies on identifying crossover events—instances where a patient’s response differed from the preceding patient’s response (either successful insertion followed by unsuccessful insertion or the reverse). We calculated each crossover value as the midpoint between the end-tidal sevoflurane concentrations. The final MACLMA for each group was derived by averaging all crossover values.

    For secondary outcomes, we assessed anesthesia induction quality using a validated 4-point scale (1 = uncooperative behavior requiring physical restraint; 4 = full cooperation or sleep state with mask acceptance).18 Emergence delirium was assessed during the first 30 minutes of recovery using the Pediatric Anesthesia Emergence Delirium scale, with scores ≥10 indicating clinically significant delirium.19 Emergence time was defined as the interval from sevoflurane discontinuation to purposeful movement in response to verbal commands. Discharge readiness from the PACU was evaluated using the modified Aldrete scoring system (threshold ≥9).20 Parental satisfaction was assessed 24 hours postoperatively using a 5-point Likert scale (1 = very dissatisfied; 5 = very satisfied).21 Finally, behavioral changes were evaluated three days after surgery via telephone interview using the Post-Hospitalization Behavior Questionnaire for Ambulatory Surgery.22

    Adverse events were systematically documented using standardized forms throughout the perioperative period. Monitored complications included bradycardia, hypotension, laryngospasm, hypoxemia, postoperative nausea and vomiting, and nightmares. All outcome assessments were performed by a single investigator blinded to treatment allocation to ensure consistency and minimize bias.

    Sample Size and Statistical Analysis

    Based on Dixon’s up-and-down methodology, dose-response studies typically require 24–26 participants to obtain six crossover points.23 Following recent methodological guidance,24 implemented a fixed prespecified sample size rather than a random stopping rule. We included 30 participants in each treatment group to enhance statistical reliability and account for potential withdrawals.

    Statistical analyses followed a predetermined plan. Data normality was assessed using the Shapiro–Wilk test. Continuous data are presented as mean ± standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables. Categorical data are expressed as frequencies and percentages. We determined the sevoflurane MACLMA using Dixon’s method and verified it through probit regression analysis.

    Between-group comparisons employed appropriate parametric or non-parametric tests based on data distribution. One-way ANOVA with Bonferroni-adjusted post-hoc tests was applied to normally distributed variables, while the Kruskal–Wallis test, followed by Dunn’s test with Bonferroni adjustment, was used for non-normally distributed data. Categorical outcomes, including emergence delirium, behavioral changes, and adverse events, were analyzed using chi-square or Fisher’s exact tests as appropriate. All analyses were performed using IBM SPSS Statistics version 27 (IBM Corp., Armonk, NY, USA), with statistical significance set at p < 0.05 (two-tailed).

    Results

    Between November 2023 and September 2024, we screened 98 children for study participation, with 90 meeting the eligibility criteria for randomization. Following protocol exclusions, the final analysis included 28 patients in the control group, 28 in the esketamine 0.5 mg/kg group, and 29 in the esketamine 1.0 mg/kg group (Figure 1). Demographic and baseline characteristics were similar across all groups (Table 1).

    Table 1 Baseline Characteristics

    Figure 1 Consolidated Standards of Reporting Trials (CONSORT) flow diagram.

    Our primary finding showed that intranasal esketamine premedication reduced the MACLMA of sevoflurane in a dose-dependent manner. These concentrations were 2.16% ± 0.18% (control, Figure 2A), 1.87% ± 0.17% (esketamine 0.5 mg/kg, Figure 2B), and 1.50% ± 0.19% (esketamine 1.0 mg/kg, Figure 2C), representing reductions of 13.4% and 30.6% from the control value, respectively. Probit regression analysis validated these findings, yielding comparable values of 2.06% (95% confidence interval [CI]: 1.85–2.26%) for control, 1.77% (95% CI: 1.60–1.95%) for esketamine 0.5 mg/kg, and 1.42% (95% CI: 1.27–1.59%) for esketamine 1.0 mg/kg groups (Figure 3).

    Figure 2 Individual responses to laryngeal mask airway insertion determined by Dixon’s up-and-down method.

    Notes: Sequential plots showing patient responses to laryngeal mask airway insertion across three treatment groups: (A) control, (B) esketamine 0.5 mg/kg, and (C) esketamine 1.0 mg/kg. Hollow circles represent successful insertions, while solid circles indicate unsuccessful insertions (characterized by movement, coughing, or bucking within one minute of placement). The horizontal dashed lines indicate the calculated minimum alveolar concentration of sevoflurane required for laryngeal mask airway insertion: 2.16% ± 0.18% (control group), 1.87% ± 0.17% (esketamine 0.5 mg/kg group), and 1.50% ± 0.19% (esketamine 1.0 mg/kg group). These values demonstrate a dose-dependent reduction in sevoflurane requirements with intranasal esketamine premedication.

    Figure 3 Probability curves for successful laryngeal mask airway insertion.

    Notes: Probit regression analysis showing the probability of successful laryngeal mask airway insertion relative to sevoflurane concentration. Three treatment groups are represented: control (light red line), esketamine 0.5 mg/kg (medium blue line), and esketamine 1.0 mg/kg (dark blue line). The horizontal dashed line at 0.5 probability (50%) intersects with each curve at the minimum alveolar concentration value: 2.06% for control, 1.77% for esketamine 0.5 mg/kg, and 1.42% for esketamine 1.0 mg/kg. The progressive leftward shift of the curves with increasing esketamine dosage illustrates the dose-dependent reduction in sevoflurane requirements.

    The clinical benefits of esketamine extended beyond anesthetic reduction. Secondary outcomes revealed clear dose-dependent effects favoring the higher dose (Table 2). The 1.0 mg/kg group showed significantly improved cooperation during anesthesia induction compared to the control (p < 0.001), while the 0.5 mg/kg group showed no difference (p = 0.756). This dose-dependent pattern persisted through recovery: only the higher dose significantly reduced emergence delirium incidence (13.8% versus 46.4%, p = 0.007) and postoperative negative behavioral changes at day 3 (20.7% versus 53.6%, p = 0.010). Parents whose children received the higher dose reported significantly greater satisfaction (p = 0.022).

    Table 2 Secondary Outcomes

    Importantly, these benefits came without compromising safety or prolonging recovery. Emergence times and PACU discharge readiness were similar across all treatment groups (p = 0.331 and p = 0.589, respectively). The incidence of adverse events (including bradycardia, hypotension, laryngospasm, hypoxemia, postoperative nausea and vomiting, and nightmares) showed no significant differences between groups, and no serious complications occurred throughout the study.

    Discussion

    Our findings demonstrate that intranasal esketamine premedication significantly reduces sevoflurane requirements during LMA insertion in pediatric patients in a dose-dependent manner. Both tested dosages (0.5 mg/kg and 1.0 mg/kg) produced clinically meaningful reductions compared to the control, with the higher dose providing approximately twice the effect. The 1.0 mg/kg dose conferred additional clinical benefits beyond anesthetic sparing, including enhanced induction cooperation, decreased emergence delirium, and reduced postoperative negative behavioral changes at day 3 postoperatively. Crucially, these advantages were achieved without extending recovery time or increasing adverse events.

    These results build upon established research on NMDA in anesthesia practice. Chen et al showed that low-dose ketamine effectively reduces sevoflurane requirements for suppressing adrenergic responses during surgical procedures,25 while Hamp et al26 reported similar dose-dependent reductions with S-ketamine administration. Our findings advance this knowledge by demonstrating that the intranasal route achieves comparable anesthetic-sparing effects to intravenous administration while offering distinct advantages for pediatric patients, particularly avoiding injection-related distress. The observed dose-dependent relationship is consistent with known NMDA receptor antagonism pharmacological principles.

    Beyond anesthetic reduction, our study revealed important behavioral benefits. Intranasal esketamine at 1.0 mg/kg significantly reduced emergence delirium (13.8% versus 46.4%) and subsequent behavioral disturbances (20.7% versus 53.6%). These improvements align with Chen et al27 who demonstrated that intravenous ketamine infusion (1 mg/kg bolus followed by 1 mg/kg/h infusion) reduced emergence delirium from 46% to 22% in children. Several mechanisms may explain these findings. Esketamine’s anti-inflammatory properties could counteract surgery-induced neuroinflammation linked to postoperative behavioral changes.28,29 Furthermore, esketamine’s neuroprotective effects may reduce physiological stress responses to surgical and anesthetic stimuli, potentially protecting the developing brain from adverse changes.30,31

    Several factors limit the interpretation of our results. The absence of pharmacokinetic measurements precluded detailed characterization of intranasal esketamine absorption profiles. Although we selected a 20-minute premedication interval based on published data indicating peak sedative effects at approximately 16 minutes,11 this fixed timing may not have captured peak drug concentrations in all patients. Our single-center design involving a specific patient population undergoing eye muscle surgery may limit applicability to other pediatric surgical contexts. Testing only two doses provides incomplete information about the optimal dose across different age groups. Additionally, the varying sevoflurane concentrations required by the Dixon methodology could theoretically affect secondary outcomes, although the substantial separation between group values makes this unlikely. Finally, despite careful blinding protocols, esketamine’s recognizable clinical effects may have compromised blinding in some cases.

    Nevertheless, our study maintains high methodological standards. The randomized, double-blind, placebo-controlled design ensures robust internal validity. The Dixon sequential allocation method provided precise measurements of anesthetic requirement while protecting children from inappropriate depth. Our comprehensive pharmacodynamic and clinical outcomes assessment offers practitioners complete information about intranasal esketamine’s effects. This approach demonstrates the quantitative reduction in sevoflurane requirements and the meaningful clinical improvements in children’s perioperative experience.

    Conclusion

    Intranasal esketamine premedication significantly reduces sevoflurane requirements for LMA insertion in pediatric patients, with the 1.0 mg/kg dose achieving optimal results: 30.6% reduction in anesthetic requirements, improved induction cooperation, and decreased emergence agitation without prolonging recovery. These findings offer clinicians an evidence-based strategy to minimize volatile anesthetic exposure while maintaining airway safety. Although our single-center study involved a specific population undergoing strabismus surgery with one experienced operator, the results demonstrate clear clinical benefits. Future multicenter trials with diverse populations and practitioners should validate these findings and optimize dosing across age groups. Nevertheless, our data establish intranasal esketamine as a valuable tool for enhancing both safety and efficacy in pediatric anesthesia practice.

    Data Sharing Statement

    The corresponding author (Yanling Liao, Email: [email protected]) will make the deidentified participant data supporting this study’s findings available upon reasonable request with a methodologically sound proposal. Data will become accessible six months after publication and remain available for three years thereafter. Requestors will be required to sign a data access agreement.

    Acknowledgments

    We sincerely thank Professor Yusheng Yao for his valuable guidance, and all participating children and their families for their cooperation. Throughout this study, we also acknowledge the dedicated support provided by the anesthesiologists, surgeons, and nursing staff at Fujian Provincial Hospital.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    This study was funded by the Science and Technology Program of Haicang District of Xiamen, China (No. 350205Z20232004), Natural Science Foundation of Xiamen, China (No. 3502Z202374068), the Fujian Provincial Health Technology Project (No. 2024CXA046), the Special Project of the National Natural Science Foundation Basic Research Enhancement Program (No. JCZX202404), and the Joint Funds for the Innovation of Science and Technology, Fujian Province (No. 2023Y9309).

    Disclosure

    The authors declare no conflicts of interest in this work.

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    12. Zhang BS, Zhang XJ, Wang CA. The efficacy and safety of esketamine in pediatric anesthesia: a systematic review and meta-analysis. Asian J Surg. 2023;46(12):5661–5663. doi:10.1016/j.asjsur.2023.08.073

    13. Hebbar KC, Reddy A, Luthra A, et al. Comparison of the efficacy of intranasal atomized dexmedetomidine versus intranasal atomized ketamine as a premedication for sedation and anxiolysis in children undergoing spinal dysraphism surgery: a randomized controlled trial. Eur J Anaesthesiol. 2024;41(4):288–295. doi:10.1097/EJA.0000000000001936

    14. Hopewell S, Chan AW, Collins GS, et al. CONSORT 2025 statement: updated guideline for reporting randomized trials. BMJ. 2025;389:e081123. doi:10.1136/bmj-2024-081123

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    21. Sam CJ, Arunachalam PA, Manivasagan S, et al. Parental satisfaction with pediatric day-care surgery and its determinants in a tertiary care hospital. J Indian Assoc Pediatr Surg. 2017;22(4):226–231. doi:10.4103/jiaps.JIAPS_212_16

    22. Jenkins BN, Kain ZN, Kaplan SH, et al. Revisiting a measure of child postoperative recovery: development of the post hospitalization behavior questionnaire for ambulatory surgery. Paediatr Anaesth. 2015;25(7):738–745. doi:10.1111/pan.12678

    23. Görges M, Zhou G, Brant R, et al. Sequential allocation trial design in anesthesia: an introduction to methods, modeling, and clinical applications. Paediatr Anaesth. 2017;27(3):240–247. doi:10.1111/pan.13088

    24. Oron AP, Souter MJ, Flournoy N. Understanding research methods: up-and-down designs for dose-finding. Anesthesiology. 2022;137(2):137–150. doi:10.1097/ALN.0000000000004282

    25. Chen C, Pang Q, Tu A, et al. Effect of low-dose ketamine on MAC BAR of sevoflurane in laparoscopic cholecystectomy: a randomized controlled trial. J Clin Pharm Ther. 2021;46(1):121–127. doi:10.1111/jcpt.13263

    26. Hamp T, Baron-Stefaniak J, Krammel M, et al. Effect of intravenous S-ketamine on the MAC of sevoflurane: a randomized, placebo-controlled, double-blinded clinical trial. Br J Anaesth. 2018;121(6):1242–1248. doi:10.1016/j.bja.2018.08.023

    27. Chen JY, Jia JE, Liu TJ, et al. Comparison of the effects of dexmedetomidine, ketamine, and placebo on emergence agitation after strabismus surgery in children. Can J Anaesth. 2013;60(4):385–392. doi:10.1007/s12630-013-9886-x

    28. Tu W, Yuan H, Zhang S, et al. Influence of anesthetic induction of propofol combined with esketamine on perioperative stress and inflammatory responses and postoperative cognition of elderly surgical patients. Am J Transl Res. 2021;13(3):1701–1709.

    29. Wang T, Weng H, Zhou H, et al. Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex. J Affect Disord. 2022;307:97–107. doi:10.1016/j.jad.2022.03.072

    30. Luo T, Deng Z, Ren Q, et al. Effects of esketamine on postoperative negative emotions and early cognitive disorders in patients undergoing non-cardiac thoracic surgery: a randomized controlled trial. J Clin Anesth. 2024;95:111447. doi:10.1016/j.jclinane.2024.111447

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  • Two Consecutive Holidays Announced in Islamabad

    Two Consecutive Holidays Announced in Islamabad

    The Islamabad Capital Territory (ICT) administration has declared Wednesday, August 13, 2025, as a local holiday within the revenue limits of the federal capital.

    The notification, issued by the Office of the District Magistrate on August 12, states that the holiday will apply to all offices except those providing essential services, including the Metropolitan Corporation Islamabad (MCI), Capital Development Authority (CDA), ICT Administration, ICT Police, Islamabad Electric Supply Company (IESCO), Sui Northern Gas Pipelines Limited (SNGPL), and hospitals.

    The District Magistrate has directed that the notification be circulated to relevant federal ministries, departments, and media outlets to ensure public awareness.

    It is worth noting that August 14, 2025, will also be observed as a public holiday to mark Pakistan’s Independence Day. This means residents of Islamabad will enjoy two consecutive days off on August 13 and 14.


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  • Pillar Two tax risk insurance – Irish market considerations

    Pillar Two tax risk insurance – Irish market considerations

    2. Pillar Two

    Pillar Two aims to create a fairer and more stable international tax system by protecting the tax base and curbing tax avoidance by multinational corporations. The publication of the Global Anti-Base Erosion Model Rules (Pillar Two) by the OECD in December 2021, outlined a global minimum taxation for international companies. It was implemented in Ireland in 2023 by way of Section 94 of the Finance (No.2) Act 2023’s insertion of (a new) Part 4A of the Taxes Consolidation Act (TCA) 1997.

    The regulatory framework of Pillar Two stipulates that in certain cases, a top-up tax must be levied on large multinational companies. To determine this tax, the tax base ‘GloBE Income’ is set in relation to the predefined recorded taxes ‘Adjusted Covered Taxes’. This allows for the identification of the states in which a multinational group of companies (MNE Group) is subject to an effective tax rate of less than 15%. When a group of companies has an effective tax rate of less than 15% in a certain country, a top-up tax is generally levied at the level of the ultimate group company within the framework of the ‘Income Inclusion Rule’ (IIR) and ‘Qualified Domestic Top Up Tax’ (QDTT). In the event that the low taxation is not (or is not fully) compensated for by the IIR, the ‘Undertaxed Profits Rule’ (UTPR) applies, the aim being to raise the effective tax rate of multinational groups to a minimum of 15%. However, the top-up tax is only calculated after deduction of a substance-related discount, so that ultimately only the ‘excess’ profit is subject to taxation.

    In the Irish context, Pillar Two’s target group and addressees are constituent entities located in Ireland that are part of an MNE Group. The prerequisite for designation as an MNE Group is that it achieves a turnover threshold of at least €750 million in the consolidated financial statements of the ‘Ultimate Parent Entity’ in at least two of the four previous financial years.

    Though simple in theory, in practice, there is considerable scope for uncertainty as by implementing these rules into Irish tax law, new laws have been introduced (which require interpretation), and ordinary accounting is interrupted by the increased administrative burden of the minimum tax assessment. The starting point for the calculation of GloBE Income is the result of the included group entity according to the annual financial statements (before consolidations of intra-group transactions). The result of the included company is generally to be calculated in accordance with the accounting standard used in the preparation of the consolidated financial statements of the group parent company. In addition, there are various adjustments and voting rights which must be carefully exercised. For example, uncapitalized tax deferrals on loss carryforwards can lead to an effective tax rate of less than 15% in the year of loss offsetting. This would trigger the application of Pillar Two provisions, and so the delta between the actual tax rate and the 15% minimum rate would be subject to tax.

    Some uncertainties can be preempted or clarified in Irish tax law by way of Revenue Opinions or Confirmations in accordance with Tax and Duty Manuals Part 37-00-40. However, the parameters for seeking a Revenue Opinion are relatively narrow. The question therefore arises as to whether Pillar Two risks can be insured.

    Pillar Two coverage: W&I insurance or tax insurance

    Two types of policies can be used to insure tax risks:

    • Warranty and indemnity (W&I) insurance, which is used to insure unknown tax risks that emanate from events in the past. Placed in the context of a corporate transaction, the provisions of W&I insurance are linked to the warranties and indemnities provided by a seller to a buyer in a sale and purchase agreement. A significant part of the cover is protection in the event that a seller has not disclosed relevant information to a buyer, or for risks which have not been discovered in due diligence.
    • Tax insurance is a form of standalone insurance that covers both known and unknown tax risks that have arisen in the past or may arise in the future. It has a much broader scope of application than W&I insurance and so can cover tax risks outside of an M&A transaction, e.g.  those risks for which a resolution might otherwise be sought by seeking a Revenue Opinion or Confirmation.

    Insurer appetite — W&I Insurance

    Approximately a third of insurers are willing to provide insurance cover for tax risks related to Pillar Two under a W&I insurance policy. Another third have clear reservations about providing coverage under W&I insurance, while the final third have yet to take a position. A list of reasons for the reluctance to offer tax cover under a W&I insurance policy includes:

    • Pillar Two being typically outside of the scope of tax due diligence
    • Lack of experience or lack of market consensus
    • The accounting standard may lead to risk allocation uncertainty (in the context of de-/first-time consolidation)
    • Liability for a third-party tax is difficult to assess without considering the position of both sides of a transaction
    • Certain issues are outside of the control of the parties (such as which countries have implemented the rules)
    • Uncertainty regarding political decision-making on Pillar Two implementation 

    Insurer appetite — Tax insurance

    The picture as relates to standalone tax insurance is clearer, and here there is a general willingness among insurers active in the Irish market to provide cover for Pillar Two risks. Insurers will consider areas such as:

    • Risks around inconsistency in implementation and interpretation in national law or tax authority commentary.
    • The Group’s use of Safe Harbor Rules.1
    • Risks related to the question of whether the non-consolidation of MNE Groups/units of companies is correct (this is likely to be particularly relevant at the time of first filing Pillar Two returns).

    The majority of insurers surveyed will consider covering known Pillar Two risks under a tax insurance policy.

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  • Football transfer rumours: Real Madrid’s Rodrygo to join Manchester City? | Transfer window

    Football transfer rumours: Real Madrid’s Rodrygo to join Manchester City? | Transfer window

    Pep Guardiola is the foremost football genius of his generation, revolutionising the game with imaginative tactics such as having the best players and the most money. But he has a particular expertise when it comes to wingers: consider Jack Grealish, now binned to Everton; Savinho, in the process of being binned to Spurs; Jérémy Doku, once fun, now ineffective; Julián Alvarez, binned to be brilliant at Atlético Madrid; Ferran Torres, binned after two seasons; Nolito, binned to Sevilla after a season; all acquired for a combined total of roughly £234.4m.

    Consequently, one can only imagine Rodrygo’s excitement at the prospect of joining Manchester City from Real Madrid, who have decided that, though he offers goals, assists, energy, effort, experience, selflessness, variety, balance and big-game performances, he simply isn’t famous enough or attention-seeking enough to remain part of their squad. They value him at £87m – or, if he moves to the Etihad, £29.99 in two years’ time.

    None of this is to decry Guardiola’s expertise when it comes to midfielders: in other City news, James McAtee is the latest to be deemed sub-par, following Cole Palmer, Morgan Rogers and Roméo Lavia out of the club. Nottingham Forest are close to agreeing a deal for the 22-year-old and, having paid £52m for Anthony Elanga, expect the price to be somewhere in the region of £9067m; Matheus Nunes, Nico González and Matteo Kovacic are all expected to remain in situ.

    Elsewhere Chelsea are, of course, in the market. They are contemplating a bid for Piero Hincapié, the Bayer Leverkusen centre-back, but any move may be affected by their apparent antipathy towards Newcastle. Having already deprived them of João Pedro and Liam Delap, they are now trying to give Liverpool £43m for Ibrahima Konaté because, as last season proves, a frequently injured and inattentive defender is a mark of champions. Though this profile would need replacing, Arne Slot might well repurpose some loot for the acquisition of Alexander Isak, who will only contemplate reintegrating or signing a new contract if he is informed there is no prospect of a move to Anfield.

    Meantime, the feelgood story of the summer continues apace as Eddie Howe seeks a centre-forward, any centre-forward, prepared to play for him. As such, Newcastle are talking to Rennes about Arnaud Kalimuendo … but so too are Brentford, whose negotiations are the more advanced. Stay tuned for yet more heartwarming hilarity.

    Howe is also interested in Bilal El Khannouss, Leicester’s attacking midfielder, but so are Leeds, while Everton, having been rebuffed in various attempts to sign Tyler Dibling, will instead try for Tyler Durden. Should he fail to materialise, they too will contact the KP Stadium, with Abdul Fatawu the target.

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    Down the East Lancs Road and to Old Trafford where, holding a placard reading “I AM THE TRUTH”, Rasmus Højlund has chained himself to the Manchester United team bus; shortly afterwards, Ruben Amorim ordered its sending to the breaker’s yard. However there is interest in the player from Italy, with Inter, Roma and Juventus joining Milan in the chase, but the smart money is on him joining his fellow reject Scott McTominay at Napoli and proving once again the old adage that when you leave United, the only way is stratospheric. Maybe they’ve got more in common with City than they think.

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  • Man Utd reveal adidas third kit for 2025/26 season

    Man Utd reveal adidas third kit for 2025/26 season

    Reimagining one of the most storied kits in our history, the design focuses on the details, from the engineered devil-base fabric to the authentic three-stripe tape and flat-knit crew collar and cuffs.

    After last year’s celebrated reintroduction of the adidas Trefoil logo on our third jersey, its return honours the logo’s historic legacy in the sport, as well as acknowledging the rising role of fashion in today’s game. 

    The black engineered base fabric features a subtle, yet striking, club devil motif, woven directly into the design, a nod to one of the most iconic symbols in our history. The modern black-and-yellow shield crest further celebrates the club’s DNA, while yellow-and-blue accents on the collar and flat-knit cuffs add a fresh twist to a classic silhouette.

    Finished with the fabled three adidas stripes in bold yellow across the shoulders and the Trefoil logo in yellow on the chest, the jersey seamlessly blends heritage with timeless adidas Originals design.

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  • Another holiday announced on August 13 – samaa tv

    1. Another holiday announced on August 13  samaa tv
    2. PSX to remain closed on August 14 for Independence Day  Profit by Pakistan Today
    3. Two Consecutive Holidays Announced in Islamabad  ProPakistani
    4. Banks to remain closed on Thursday  Associated Press of Pakistan
    5. Four-day school holiday announced in Sindh from Aug 15  nation.com.pk

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  • This is the Tivoli Stadion Tirol – realmadrid.com

    This is the Tivoli Stadion Tirol – realmadrid.com

    1. This is the Tivoli Stadion Tirol  realmadrid.com
    2. Soccer – Spain: Real Madrid train ahead of final against WSG Tirol  ptv.com.pk
    3. Just in – Real Madrid superstar out of WSG Tirol clash; teenager called up as replacement  Madrid Universal
    4. Real Madrid dealt another major injury blow just days before season opener  The Real Champs
    5. Real Madrid midfield heavyweight hoping to be ready for Osasuna clash after fitness setback  Yahoo Sports

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  • China may have put up another hurdle for Nvidia to overcome

    China may have put up another hurdle for Nvidia to overcome

    By Barbara Kollmeyer

    Report says China telling companies not to buy Nvidia’s H20 chips

    China is reportedly dissuading companies from purchasing Nvidia’s H20 chips.

    Nvidia’s rock-and-a-hard place position on selling AI chips to China might have just worsened, as that country has reportedly told companies not to buy them.

    Notifications have been sent to several firms, dissuading them from using the H20 processors, which Nvidia (NVDA)developed specifically for the Chinese market, Bloomberg reported Tuesday, citing sources. That especially applies to any company using the processors related to any government activity, the report added.

    The purported development follows a Financial Times report on Sunday that Nvidia and Advanced Micro Devices had worked out a deal to give 15% of revenue from China chip sales to the U.S. government in exchange for export licenses to sell in the country again.

    Analysts have said that such a deal would set a dangerous precedent for those companies by paying the U.S. government to sell their own chips. Nvidia’s H20 and AMD’s MI308 chips were designed specifically to meet U.S. export rules, but were banned from selling those to China in April by the administration of U.S. President Donald Trump.

    Read: Nvidia and AMD reportedly strike deals with Trump – but analysts see a ‘slippery slope’

    Sources told Bloomberg that China’s apparent reluctance to allow companies to purchase Nvidia’s H20 chip also applies to AI accelerators from AMD, though the report said it’s not clear if the guidelines also apply to its MI308 chips.

    Bloomberg reached out to China’s Ministry of Industry and Information Technology and the Cyberspace Administration of China for comment, but neither responded. MarketWatch has reached out to Nvidia and AMD for comment.

    Shares of both companies were tilting modestly lower ahead of Tuesday’s open, according to Robinhood. Monday saw Nvidia stock fall 0.3% and AMD lose 0.2%.

    -Barbara Kollmeyer

    This content was created by MarketWatch, which is operated by Dow Jones & Co. MarketWatch is published independently from Dow Jones Newswires and The Wall Street Journal. 

    
  (END) Dow Jones Newswires
    

    
  08-12-25 0337ET
    

    Copyright (c) 2025 Dow Jones & Company, Inc.

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  • US Stock Futures Waver in Lead-Up to CPI Print: Markets Wrap

    US Stock Futures Waver in Lead-Up to CPI Print: Markets Wrap


    This content was published on

    (Bloomberg) — US stock futures edged higher, mirroring the subdued tone across most asset classes, as investors stayed on the sidelines ahead of Tuesday’s inflation report that could reshape expectations for interest rate cuts.

    Contracts for the S&P 500 rose 0.2%. The dollar traded flat. US Treasuries saw muted action with the yield on 10-year notes dropping less than one basis point to 4.28%. Gold ticked higher.

    Europe’s Stoxx 600 index rose 0.3% as luxury names outperformed after Washington extended a trade truce with Beijing. A gauge for Asian stocks advanced 0.5%.

    Tuesday’s inflation report arrives after traders in recent weeks ramped up expectations for Federal Reserve policy easing this year, aiming to bolster a labor market showing signs of softening. Still, investors remain attuned to the risk of persistent price pressures — particularly in the face of shifting US tariff policies — and the potential for a stagflationary backdrop.

    Money markets show traders have priced in more than two rate cuts by December, with about an 80% probability of a quarter-point reduction next month. The core consumer price index, regarded as a measure of underlying inflation because it strips out volatile food and energy costs, is expected to show a 0.3% increase for July, compared to 0.2% in the previous month.

    “If we get a continued slowdown in the employment picture, we expect the Fed to deliver rate cuts even in the face of sticky inflation,” said Mohit Kumar, chief European strategist at Jefferies International. “However, a sticky inflation picture will prevent an aggressive easing policy.”

    Markets Live Strategist Garfield Reynolds says:

    Global equities look nervous heading into Tuesday’s US CPI release, given the potential the data could disrupt expectations for Fed interest-rate cuts that have helped to prop up risk appetite in the US and beyond. Asian stocks may face a more perilous risk-reward set up given this local investor hesitance.

    Meanwhile, China urged local companies to avoid using Nvidia’s H20 processors, particularly for government-related purposes. The move will complicate the chipmaker’s attempts to recoup billions in lost China revenue as well as the Trump administration’s unprecedented push to turn those sales into a US government windfall.

    Some of the main moves in markets:

    Stocks

    The Stoxx Europe 600 rose 0.3% as of 8:28 a.m. London time S&P 500 futures rose 0.2% Nasdaq 100 futures rose 0.1% Futures on the Dow Jones Industrial Average rose 0.2% The MSCI Asia Pacific Index rose 0.5% The MSCI Emerging Markets Index was little changed Currencies

    The Bloomberg Dollar Spot Index was little changed The euro was little changed at $1.1616 The Japanese yen fell 0.1% to 148.32 per dollar The offshore yuan was little changed at 7.1956 per dollar The British pound rose 0.1% to $1.3446 Cryptocurrencies

    Bitcoin rose 0.2% to $119,132.36 Ether rose 1.6% to $4,314.48 Bonds

    The yield on 10-year Treasuries was little changed at 4.28% Germany’s 10-year yield was little changed at 2.70% Britain’s 10-year yield advanced three basis points to 4.60% Commodities

    Brent crude rose 0.4% to $66.89 a barrel Spot gold rose 0.1% to $3,347.30 an ounce This story was produced with the assistance of Bloomberg Automation.

    –With assistance from Anand Krishnamoorthy.

    ©2025 Bloomberg L.P.

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  • Missing Cosmic Lithium Problem Could Still Point To New Physics

    Missing Cosmic Lithium Problem Could Still Point To New Physics

    Lithium, currently in such high demand for electric vehicles and smart phones, also continues to push astrophysical theory to the limit. Known as the Cosmological Lithium Problem, the primordial abundance of this light metal has puzzled astrophysicists for more than two decades now. And the eventual solution to this conundrum might require new physics.

    The crux of the issue is the observed underabundance of Lithium-7, a stable isotope of Lithium that consists of three protons and four neutrons.

    For every nucleus of lithium, there are two billion nuclei of hydrogen in the early universe, Andreas Korn, a stellar astrophysicist at Uppsala University in Sweden, tells me in Stockholm.

    And among old galactic halo stars, the Lithium-7 underabundance is a factor of two to three below big bang nucleosynthesis predictions. That is, the process that (within the first three minutes after the big bang) produced the first light elements — hydrogen, helium, and tiny amounts of lithium and beryllium.

    Lithium is not a rare earth element, but it is a very rare element in the cosmos — about nine orders of magnitude less than hydrogen and five orders of magnitude less than oxygen in the present-day universe.

    Why Does This Matter?

    The Lithium-7 problem is important because it poses the only remaining inconsistency in big bang nucleosynthesis, says Korn. Too much Lithium-7 was produced in the big bang, and we see too little of it in old stars, he says.

    If it’s not solved through conventional theory, then the door will inherently be left ajar for new physics.

    Defining the true nature of the universe’s exotic dark matter, for instance, through big bang nucleosynthesis or some other observation would represent a revolution in fundamental physics, says Korn.

    Physicists know that the standard model of particle physics is not complete.

    Unsurprisingly, we physicists are looking for clues other than the gravitational effects of the cosmos’ missing exotic dark matter to further constrain the realm of new physics, says Korn. Discrepancies in BBN could provide such clues, he says.

    The hope has been that such an extension of conventional physics could at the same time explain the cosmos’ elusive dark matter.

    The Lithium problem was aptly described in a 2011 review paper.

    In a paper appearing in the journal Annual Reviews of Nuclear and Particle Science, author Brian Fields notes that BBN represents our earliest reliable probe of the cosmos. However, Lithium-7 observations lie at least a factor of three below predictions, he writes.

    And in the last 14 years since Fields’ paper was published, there has only been incremental progress in resolving this Lithium-7 discrepancy.

    Precise observations of solar neutrinos also point to new physics.

    Nuclear reaction networks applied to the Sun predict how many neutrinos are created in the fusion reactions, but it turns out that the number of electron neutrinos falls short of expectations, says Korn. They are changed to other types of neutrinos on the way to us, through a process called neutrino oscillations, he says.

    BBN also tells us that there were three neutrino types present in the early universe. Any discrepancy between BBN predictions and observations could, in principle, provide such clues for new physics.

    But there is a possibility that most of this problem is simply solved by conventional stellar physics, says Korn.

    In BBN, Lithium represents only a trace element. In the Sun, 99.5% of the lithium is gone because it has been mixed down to layers that are hotter than two and a half million degrees Kelvin, and that Lithium has disintegrated.

    Tracing Old Stars

    Halo stars are very old, metal poor stars on the outskirts of our own Milky Way Galaxy that can trace the state of the universe as it was 10 or 12 billion years ago, says Korn.

    Stellar Mixing

    But the challenge is that astronomers have a hard time determining how much lithium and other elements have been mixed deep into the interior of the target star. In particular, theorists need to know how much mixing of lithium occurs at the boundary between the star’s outer convective envelope and its stellar interior.

    As in a hot pot of soup, stellar material that is brought to the bottom of the convection zone reaches temperatures of two and a half million Kelvin and subsequently destroyed, says Korn.

    Hard Work

    Korn says that particle physicists, nuclear theorists and observational astrophysicists have all had their nose to the grindstone, trying to resolve this lithium-7 underabundance issue for decades now.

    It’s important to understand just how much lithium is depleted by stars because only then can we scientifically address the remaining cosmological lithium problem, says Korn.

    Future Observations

    In a 2021 paper published in the journal Experimental Astronomy, the authors write that a proposed European Space Agency mission known as HAYDN (High precision AsteroseismologY of DeNse stellar fields) would potentially see launch by mid-century. If so, it would observe stars in metal-poor globular clusters in both our own Milky Way Galaxy and nearby dwarf galaxies.

    The HAYDN mission will be crucial to getting a better handle on the real abundance of Lithium in the Milky Way and nearby dwarf galaxies like the Large and Small Magellanic Clouds via a process known as asteroseismology which uses stellar oscillations (literally seismic waves inside a star) to probe its interior.

    These space-based observations, says Korn, would help theorists place better constraints on just how much lithium-7 is being destroyed in stellar interiors.

    A Stellar Solution?

    I’m upholding the idea that at least part, or even a significant part, of the problem is a stellar problem, says Korn. But it remains a hard nut to crack, he says.

    ForbesNew Book Reveals Backstories Of Cosmic HistoryBy Bruce Dorminey

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