Ergodicity Breaking Provably Robust to Arbitrary Perturbations.

We present a new route to ergodicity breaking via Hilbert space fragmentation that displays an unprecedented level of robustness. Our construction relies on a single emergent (prethermal) conservation law. In the limit when the conservation law is exact, we prove the emergence of Hilbert space fragmentation with an exponential number of frozen configurations. These configurations are low-entanglement states in the middle of the energy spectrum and therefore constitute examples of quantum many-body scars. We further prove that every frozen configuration is absolutely stable to arbitrary perturbations, to all finite orders in perturbation theory. In contrast to previous constructions, our proof is not limited to symmetric perturbations, or to perturbations with compact support, but also applies to perturbations with long-range tails, and even to arbitrary geometrically nonlocal k-body perturbations, as long as k/L→0 in the thermodynamic limit, where L is linear system size. Additionally, we identify one-form U(1) charges characterizing some nonfrozen sectors, and discuss the dynamics starting from typical initial conditions, which we argue is best interpreted in terms of the magnetohydrodynamics of the emergent one-form symmetry.

Shooting the messenger: a systematic review investigating extracellular vesicle isolation and characterisation methods and their influence on understanding extracellular vesicles-radiotherapy interactions in glioblastoma.

BACKGROUND: Extracellular vesicles (EVs) hold promise for improving our understanding of radiotherapy response in glioblastoma due to their role in intercellular communication within the tumour microenvironment (TME). However, methodologies to study EVs are evolving with significant variation within the EV research community. METHODS: We conducted a systematic review to critically appraise EV isolation and characterisation methodologies and how this influences our understanding of the findings from studies investigating radiotherapy and EV interactions in glioblastoma. 246 articles published up to 24/07/2023 from PubMed and Web of Science were identified using search parameters related to radiotherapy, EVs, and glioblastoma. Two reviewers evaluated study eligibility and abstracted data. RESULTS: In 26 articles eligible for inclusion (16 investigating the effects of radiotherapy on EVs, five investigating the effect of EVs on radiation response, and five clinical studies), significant heterogeneity and frequent omission of key characterisation steps was identified, reducing confidence that the results are related to EVs and their cargo as opposed to co-isolated bioactive molecules. However, the results are able to clearly identify interactions between EVs and radiotherapy bi-directionally within different cell types within the glioblastoma TME. These interactions facilitate transferable radioresistance and oncogenic signalling, highlighting that EVs are an important component in the variability of glioblastoma radiotherapy response. CONCLUSIONS: Future multi-directional investigations interrogating the whole TME are required to improve subsequent clinical translation, and all studies should incorporate up to date controls and reporting requirements to increase the validity of their findings. This would be facilitated by increased collaboration between less experienced and more experienced EV research groups.

Prognostic implications of adaptive immune features in MMR-proficient colorectal liver metastases classified by histopathological growth patterns.

BACKGROUND: After resection, colorectal cancer liver metastases (CRLM) surrounded by a desmoplastic rim carry a better prognosis than the metastases replacing the adjacent liver. However, these histopathological growth patterns (HGPs) are insufficient to guide clinical decision-making. We explored whether the adaptive immune features of HGPs could refine prognostication. METHODS: From 276 metastases resected in 176 patients classified by HGPs, tissue microarrays were used to assess intratumoral T cells (CD3), antigen presentation capacity (MHC class I) and CD73 expression producing immunosuppressive adenosine. We tested correlations between these variables and patient outcomes. RESULTS: The 101 (57.4%) patients with dominant desmoplastic HGP had a median recurrence-free survival (RFS) of 17.1 months compared to 13.3 months in the 75 patients (42.6%) with dominant replacement HGP (p = 0.037). In desmoplastic CRLM, high vs. low CD73 was the only prognostically informative immune parameter and was associated with a median RFS of 12.3 months compared to 26.3, respectively (p = 0.010). Only in dominant replacement CRLM, we found a subgroup (n = 23) with high intratumoral MHC-I expression but poor CD3+ T cell infiltration, a phenotype associated with a short median RFS of 7.9 months. CONCLUSIONS: Combining the assessments of HGP and adaptive immune features in resected CRLM could help identify patients at risk of early recurrence.

How low can you go? Justified hesitancy and the ethics of childhood vaccination against COVID-19.

This paper explores some of the ethical issues around offering COVID-19 vaccines to children. My main conclusion is rather paradoxical: the younger we go, the stronger the grounds for justified parental hesitancy and, as such, the stronger the arguments for enforcing vaccination. I suggest that this is not the reductio ad absurdum it appears, but does point to difficult questions about the nature of parental authority in vaccination cases. The first section sketches the disagreement over vaccinating teenagers, arguing that the UK policy was permissible. The second section outlines a problem for this policy, that it faces justified vaccine hesitancy. The third section discusses three strategies for responding to this problem, arguing that there may be no simple way of overcoming parents' reasons to resist vaccinations.

Costa, cancer and coronavirus: contractualism as a guide to the ethics of lockdown.

Lockdown measures in response to the COVID-19 pandemic involve placing huge burdens on some members of society for the sake of benefiting other members of society. How should we decide when these policies are permissible? Many writers propose we should address this question using cost-benefit analysis (CBA), a broadly consequentialist approach. We argue for an alternative non-consequentialist approach, grounded in contractualist moral theorising. The first section sets up key issues in the ethics of lockdown, and sketches the apparent appeal of addressing these problems in a CBA frame. The second section argues that CBA fundamentally distorts the normative landscape in two ways: first, in principle, it allows very many morally trivial preferences-say, for a coffee-might outweigh morally weighty life-and-death concerns; second, it is insensitive to the core moral distinction between victims and vectors of disease. The third section sketches our non-consequentialist alternative, grounded in Thomas Scanlon's contractualist moral theory. On this account, the ethics of self-defence implies a strong default presumption in favour of a highly restrictive, universal lockdown policy: we then ask whether there are alternatives to such a policy which are justifiable to all affected parties, paying particular attention to the complaints of those most burdened by policy. In the fourth section, we defend our contractualist approach against the charge that it is impractical or counterintuitive, noting that actual CBAs face similar, or worse, challenges.

International female rugby union players' anthropometric and physical performance characteristics: A five-year longitudinal analysis by individual positional groups.

Longitudinal changes in anthropometric and physical performance characteristics of International female rugby union players were evaluated across 5-seasons, according to field position. Sixty-eight international female rugby union players from a top 2 ranked international team, undertook anthropometric and physical performance measurements across five seasons. Anthropometric and physical performance changes occurred, with skinfolds decreasing between 2015 and 2017 and body mass increasing between 2017 and 2019. Single-leg isometric squat (SL ISO), 0-10 m momentum (0-10 Mom) and 20-30 m momentum (20-30Mom) were higher in 2018 and 2019 than all years. Front-row players were characterised by greater SL ISO and 1-RM bench press than inside and outside backs, with higher skinfolds and lower endurance levels than all positions. Between 2017 and 2019, front-row players had larger decreases and increases in endurance and one repetition maximum (1-RM) bench press, respectively, compared to all other positions. Forwards had the highest 0-10Mom and 20-30Mom, and scrum-half the lowest, while outside backs had faster 0-10, 30-40, and 40 m (TT40 m) times, and greater peak velocity (Vmax) compared to forward positions. These longitudinal findings show that physical performance has increased, with anthropometric and performance characteristics becoming more distinctive between positions, among elite female rugby union players.

Painless expanding facial swelling.

A previously healthy 11-year-old girl sustained a mosquito bite on her right cheek while on holiday in rural Bangladesh. A painless lump developed at the site, and over the ensuing 2 months gradually expanded. She was otherwise completely asymptomatic; there was no family history of note. On examination, there was obvious swelling affecting the right cheek and visible abnormality of the upper gum with displacement of the right upper central incisor (figure 1).

Pulse flaking: Opportunities and challenges, a review.

Pulses provide economic and health benefits to people in many countries around the world; however, their adoption in western diets, particularly in processed and formulated foods, is limited. One strategy to increase the level of pulses in western diets is to improve pulse accessibility to the ready-to-eat (RTE) food market sector. Pulses have compositional and structural differences when compared to cereals and behave differently during processing. While there have been numerous studies on pulses processed using traditional processing methods, there are limited studies describing processing of pulses as a major ingredient in RTE forms such as flakes. To understand the full processing potential of pulses, systematic studies are required using commercial-scale RTE pilot processing equipment coupled with fundamental property determination techniques to evaluate the effects of processing and pulse material on pulse flake attributes. In-depth studies of pulse properties and their processability are likely to result in the production of high-quality pulse-based foods with superior health benefits. This review explores the current and potential opportunities for processing pulses with a focus on flake products. The roles of pulse type and major structure-forming components such as fiber, carbohydrates, and proteins on end-product quality of processed pulses are discussed.

Acute Neuromuscular Electrical Stimulation (NMES) With Blood Flow Restriction: The Effect of Restriction Pressures.

CONTEXT: Neuromuscular electrical stimulation (NMES) combined with blood flow restriction (BFR) has been shown to improve muscular strength and size better than NMES alone. However, previous studies used varied methodologies not recommended by previous NMES or BFR research. OBJECTIVE: The present study investigated the acute effects of NMES combined with varying degrees of BFR using research-recommended procedures to enhance understanding and the clinical applicability of this combination. DESIGN: Randomized crossover. SETTING: Physiology laboratory. PARTICIPANTS: A total of 20 healthy adults (age 27 [4] y; height 177 [8] cm; body mass 77 [13] kg). INTERVENTIONS: Six sessions separated by at least 7 days. The first 2 visits served as familiarization, with the experimental conditions performed in the final 4 sessions: NMES alone, NMES 40% BFR, NMES 60% BFR, and NMES 80% BFR. MAIN OUTCOME MEASURES: Maximal voluntary isometric contraction, muscle thickness, blood pressure, heart rate, rating of perceived exertion, and pain were all recorded before and after each condition. RESULTS: The NMES 80% BFR caused greater maximal voluntary isometric contraction decline than any other condition (-38.9 [22.3] N·m, P < .01). Vastus medialis and vastus lateralis muscle thickness acutely increased after all experimental conditions (P < .05). Pain and ratings of perceived exertion were higher after NMES 80% BFR compared with all other experimental conditions (P < .05). No cardiovascular effects were observed between conditions. CONCLUSION: The NMES combined with 80% BFR caused greater acute force decrement than the other conditions. However, greater perceptual ratings of pain and ratings of perceived exertion were observed with NMES 80% BFR. These acute observations must be investigated during chronic interventions to corroborate any relationship to changes in muscle strength and size in clinical populations.

Computationally Universal Phase of Quantum Matter.

We provide the first example of a symmetry protected quantum phase that has universal computational power. This two-dimensional phase is protected by one-dimensional linelike symmetries that can be understood in terms of the local symmetries of a tensor network. These local symmetries imply that every ground state in the phase is a universal resource for measurement-based quantum computation.

Oral taurine improves critical power and severe-intensity exercise tolerance.

This study investigated the effects of acute oral taurine ingestion on: (1) the power-time relationship using the 3-min all-out test (3MAOT); (2) time to exhaustion (TTE) 5% > critical power (CP) and (3) the estimated time to complete (Tlim) a range of fixed target intensities. Twelve males completed a baseline 3MAOT test on a cycle ergometer. Following this, a double-blind, randomised cross-over design was followed, where participants were allocated to one of four conditions, separated by 72 h: TTE + taurine; TTE + placebo; 3MAOT + taurine; 3MAOT + placebo. Taurine was provided at 50 mg kg-1, whilst the placebo was 3 mg kg-1 maltodextrin. CP was higher (P < 0.05) in taurine (212 ± 36 W) than baseline (197 ± 40 W) and placebo (193 ± 35 W). Work end power was not affected by supplement (P > 0.05), yet TTE 5% > CP increased (P < 0.05) by 1.7 min after taurine (17.7 min) compared to placebo (16.0 min) and there were higher (P < 0.001) estimated Tlim across all work targets. Acute supplementation of 50 mg kg-1 of taurine improved CP and estimated performance at a range of severe work intensities. Oral taurine can be taken prior to exercise to enhance endurance performance.

The effect of severe and moderate hypoxia on exercise at a fixed level of perceived exertion.

PURPOSE: The purpose of this study was to determine the primary cues regulating perceived effort and exercise performance using a fixed-RPE protocol in severe and moderate hypoxia. METHODS: Eight male participants (26 ± 6 years, 76.3 ± 8.6 kg, 178.5 ± 3.6 cm, 51.4 ± 8.0 mL kg- 1 min- 1[Formula: see text]O2max) completed three exercise trials in environmental conditions of severe hypoxia (FIO2 0.114), moderate hypoxia (FIO2 0.152), and normoxia (FIO2 0.202). They were instructed to continually adjust their power output to maintain a perceived effort (RPE) of 16, exercising until power output declined to 80% of the peak 30-s power output achieved. RESULTS: Exercise time was reduced (severe hypoxia 428 ± 210 s; moderate hypoxia 1044 ± 384 s; normoxia 1550 ± 590 s) according to a reduction in FIO2 (P < 0.05). The rate of oxygen desaturation during the first 3 min of exercise was accelerated in severe hypoxia (- 5.3 ± 2.8% min- 1) relative to moderate hypoxia (- 2.5 ± 1.0% min- 1) and normoxia (- 0.7 ± 0.3% min- 1). Muscle tissue oxygenation did not differ between conditions (P > 0.05). Minute ventilation increased at a faster rate according to a decrease in FIO2 (severe hypoxia 27.6 ± 6.6; moderate hypoxia 21.8 ± 3.9; normoxia 17.3 ± 3.9 L min- 1). Moderate-to-strong correlations were identified between breathing frequency (r = - 0.718, P < 0.001), blood oxygen saturation (r = 0.611, P = 0.002), and exercise performance. CONCLUSIONS: The primary cues for determining perceived effort relate to progressive arterial hypoxemia and increases in ventilation.

Seven-day ischaemic preconditioning improves muscle efficiency during cycling.

Ischaemic preconditioning (IPC) has emerged as a potential non-invasive ergogenic aid to enhance exercise performance. Repeated application of IPC has demonstrated clinical efficacy, therefore our aims were to investigate its effect on endurance cycling performance and muscle efficiency. Twenty participants undertook 7-d repeated bilateral lower limb occlusion (4 x 5-min) of IPC (220 mmHg) or sham (20 mmHg). Prior to and 72-h following the intervention, participants performed submaximal cycling at 70, 80 and 90% of ventilatory threshold (VT) followed by an incremental exercise test. IPC had no effect on V˙ O2max (P = 0.110); however, time to exhaustion increased by ~ 9% and Wmax by ~ 5 % (IPC pre 307 ± 45 to post 323 ± 51 W) relative to sham (P = 0.002). There were no changes in gross efficiency (GE) (P > 0.05); however, delta efficiency (DE) increased by 3.1% following IPC (P = 0.011). Deoxyhaemoglobin (HHb) was reduced following IPC ~ 30% (P = 0.017) with no change in total haemoglobin (tHb). Repeated IPC over 7-d enhanced muscle efficiency and extended cycling performance. The physiological effects of repeated IPC on skeletal muscle efficiency explains the notable improvements in endurance performance.

Effects of Small-Sided Game Variation on Changes in Hamstring Strength.

Madison, G, Patterson, SD, Read, P, Howe, L, and Waldron, M. Effects of small-sided game variation on changes in hamstring strength. J Strength Cond Res 33(3): 839-845, 2019-Small-sided games (SSGs) are commonly used by soccer practitioners to condition players. This form of exercise can result in fatigue, potentially exposing the muscle to injury risk. The purpose of this study was to determine the effects of SSG variations on hamstring torque in semiprofessional soccer players. In a counterbalanced cross-over design, 10 male semiprofessional soccer players took part in both small relative area (3 vs. 3; 300 m) and large relative area (4 vs. 4; 1000 m) SSGs. The games comprised 6 × 4-minute bouts, with 90-second recovery. Both movement and heart rate responses were monitored by global positioning systems (GPS) and hamstring isometric torque was measured pre-training and post-training using a NordBord. There were differences (p < 0.05) between the small and large relative area games for peak hamstring force decrement (5.78 N and -13.62 N, respectively) and mean hamstring force decrement at 90° (11.11 N and -4.78 N, respectively). The number of accelerations was related to (r = 0.46, p = 0.039) reduced hamstring peak torque at 90°. In conclusion, larger relative area SSGs elicited the greatest internal and external loads, resulting in decrements in hamstring force. The number of accelerations performed in the session increases the likelihood of hamstring fatigue and can be controlled with the relative pitch area.

The effects of acute leucine or leucine-glutamine co-ingestion on recovery from eccentrically biased exercise.

This study investigated the effects of leucine or leucine + glutamine supplementation on recovery from eccentric exercise. In a double-blind independent groups design, 23 men were randomly assigned to a leucine (0.087 g/kg; n = 8), leucine + glutamine (0.087 g/kg + glutamine 0.3 g/kg; n = 8) or placebo (0.3 g/kg maltodextrin; n = 7) group. Participants performed 5 sets of drop jumps, with each set comprising 20 repetitions. Isometric knee-extensor strength, counter-movement jump (CMJ) height, delayed-onset muscle soreness (DOMS) and creatine kinase (CK) were measured at baseline, 1, 24, 48 h and 72 h post-exercise. There was a time × group interaction for isometric strength, CMJ and CK (P < 0.05), with differences between the leucine + glutamine and placebo group at 48 h and 72 h for strength (P = 0.013; d = 1.43 and P < 0.001; d = 2.06), CMJ (P = 0.008; d = 0.87 and P = 0.019; d = 1.17) and CK at 24 h (P = 0.012; d = 0.54) and 48 h (P = 0.010; d = 1.37). The leucine group produced higher strength at 72 h compared to placebo (P = 0.007; d = 1.65) and lower CK at 24 h (P = 0.039; d = 0.63) and 48 h (P = 0.022; d = 1.03). Oral leucine or leucine + glutamine increased the rate of recovery compared to placebo after eccentric exercise. These findings highlight potential benefits of co-ingesting these amino acids to ameliorate recovery.

The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis.

PURPOSE OF REVIEW: The aims of this meta-analysis were to investigate the effects of orally administered isolated taurine on resting systolic blood pressure (SBP) and diastolic blood pressure (DBP) in humans. RECENT FINDINGS: There is growing evidence that taurine deficiency is associated with hypertension and that oral supplementation can have antihypertensive effects in humans. However, these investigations have been conducted across a number of decades and populations and have not been collectively reviewed. A search was performed using various databases in May 2018 and later screened using search criteria for eligibility. There were seven peer-reviewed studies meeting the inclusion criteria, encompassing 103 participants of varying age and health statuses. Taurine ingestion reduced SBP (Hedges' g = - 0.70, 95% CI - 0.98 to - 0.41, P < 0.0001) and DBP (Hedges' g = - 0.62, 95% CI - 0.91 to - 0.34, P < 0.0001). These results translated to mean ~ 3 mmHg reductions in both SBP (range = 0-15 mmHg) and DBP (range = 0-7 mmHg) following a range of doses (1 to 6 g/day) and supplementation periods (1 day to 12 weeks), with no adverse events reported. These preliminary findings suggest that ingestion of taurine at the stated doses and supplementation periods can reduce blood pressure to a clinically relevant magnitude, without any adverse side effects. Future studies are needed to establish the effects of oral taurine supplementation on targeted pathologies and the optimal supplementation doses and periods.

Computational Power of Symmetry-Protected Topological Phases.

We consider ground states of quantum spin chains with symmetry-protected topological (SPT) order as resources for measurement-based quantum computation (MBQC). We show that, for a wide range of SPT phases, the computational power of ground states is uniform throughout each phase. This computational power, defined as the Lie group of executable gates in MBQC, is determined by the same algebraic information that labels the SPT phase itself. We prove that these Lie groups always contain a full set of single-qubit gates, thereby affirming the long-standing conjecture that general SPT phases can serve as computationally useful phases of matter.

International validation of a urinary biomarker panel for identification of active lupus nephritis in children.

BACKGROUND: Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts. METHODS: Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy. RESULTS: A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (p c) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (p c = 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991). CONCLUSION: In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an 'excellent' ability for accurately identifying active LN in children.

Cardiovascular function during supine rest in endurance-trained males with New Zealand blackcurrant: a dose-response study.

PURPOSE: Blackcurrant contains anthocyanins that could alter cardiovascular function and reduce cardiovascular disease risk. We examined dose responses of New Zealand blackcurrant (NZBC) extract on cardiovascular function during supine rest. METHODS: Fifteen endurance-trained male cyclists (age: 38 ± 12 years, height: 178 ± 5 cm, body mass: 76 ± 10 kg, [Formula: see text]: 56 ± 8 mL kg-1 min-1, mean ± SD) were randomly assigned using a counterbalanced Latin square design to complete four conditions, a control of no NZBC, or one of three doses (300, 600 or 900 mg day-1) of NZBC extract (CurraNZ™) for 7-days with a 14-day washout. Cardiovascular function (i.e., blood pressure, heart rate, ejection time, cardiac output, stroke volume, and total peripheral resistance) during supine rest was examined (Portapres® Model 2). RESULTS: Systolic and diastolic blood pressure, heart rate and ejection time were unchanged by NZBC. A dose effect (P < 0.05) was observed for cardiac output, stroke volume, and total peripheral resistance. A trend for a dose effect was observed for mean arterial blood pressure. Cardiac output increased by 0.6 ± 0.6 L min-1 (15%) and 1.0 ± 1.0 L min-1 (28%) and stroke volume by 5 ± 8 mL (7%) and 6 ± 17 mL (18%) between control and 600, and 900 mg day-1, respectively. Total peripheral resistance decreased by 4 ± 3 mmHg L-1 min-1 (20%) and 5 ± 9 mmHg L-1 min-1 (20%) for 600, and 900 mg day-1. CONCLUSION: Seven-days intake of New Zealand blackcurrant extract demonstrated dose-dependent changes on some cardiovascular parameters during supine rest in endurance-trained male cyclists.