From non-alcoholic fatty liver disease to metabolic-associated steatotic liver disease: Rationale and implications for the new terminology.

Non-alcoholic fatty liver disease (NAFLD) was the term first used to describe hepatic steatosis in patients with the metabolic syndrome who did not consume excess amounts of alcohol. Alcoholic liver disease (ALD) has many similarities to NAFLD in both pathogenesis and histology. This entity is now the most prevalent chronic liver disease worldwide as a consequence of the epidemic of obesity. Attempts to incorporate the importance of the metabolic syndrome in the development of steatosis resulted in the renaming of NAFLD as metabolic-associated fatty liver disease. This new term, however, has the disadvantage of the use of terms that may be perceived as derogatory. The terms fatty and non-alcoholic have negative connotations in many cultures. In addition, non-alcoholic is not usually a term applicable to pediatric cases of hepatic steatosis. Recently, an international collaborative effort, with participants from 56 countries, after a global consultation process, recommended to change the nomenclature to steatotic liver disease -including metabolic dysfunction- associated steatotic liver disease, metabolic-associated steatohepatitis and metabolic dysfunction-associated ALD. The new terminology is consistent with most of the previously published epidemiological studies and will have a major impact on research into diagnosis, prognosis and treatment.

Universal Measurement-Based Quantum Computation in a One-Dimensional Architecture Enabled by Dual-Unitary Circuits.

A powerful tool emerging from the study of many-body quantum dynamics is that of dual-unitary circuits, which are unitary even when read "sideways," i.e., along the spatial direction. Here, we show that this provides the ideal framework to understand and expand on the notion of measurement-based quantum computation (MBQC). In particular, applying a dual-unitary circuit to a many-body state followed by appropriate measurements effectively implements quantum computation in the spatial direction. We show how the dual-unitary dynamics generated by the dynamics of the paradigmatic one-dimensional kicked Ising chain with certain parameter choices generate resource states for universal deterministic MBQC. Specifically, after k time steps, equivalent to a depth-k quantum circuit, we obtain a resource state for universal MBQC on ∼3k/4 encoded qubits. Our protocol allows generic quantum circuits to be "rotated" in space-time and gives new ways to exchange between resources like qubit number and coherence time in quantum computers. Beyond the practical advantages, we also interpret the dual-unitary evolution as generating an infinite sequence of new symmetry-protected topological phases with spatially modulated symmetries, which gives a vast generalization of the well-studied one-dimensional cluster state and shows that our protocol is robust to symmetry-respecting deformations.

Identification of a Safe and Tolerable Carbamazepine Dosing Paradigm that Facilitates Effective Evaluation of CYP3A4 Induction.

Carbamazepine (CBZ) is the recommended alternative to rifampicin as a CYP3A4 inducer in drug-drug interaction studies. However, the traditional CBZ dosing paradigm can lead to several adverse events (AEs). This study tested a shorter CBZ dosing regimen using the CYP3A4-sensitive index substrate midazolam (MDZ). This was a fixed-sequence arm of an open-label, phase I study (NCT04840888). Healthy participants (n = 15) aged 18-63 years received oral doses of 1.2 mg MDZ alone (Day 1), CBZ b.i.d. alone (100 mg Days 2-4; 200 mg Days 5-7; 300 mg Days 8-10 and 12-13), and 300 mg CBZ b.i.d. plus 1.2 mg MDZ (Days 11 and 14). One participant (6.7%) experienced constipation due to treatment with CBZ plus MDZ on Day 11. One participant (6.7%) experienced urticaria (Days 12-13), and two participants (13.3%) experienced somnolence (Days 8-10) due to treatment with 300 mg CBZ b.i.d. alone. All AEs were mild. For MDZ, the geometric mean (90% CI) ratio (vs. Day 1) of the area under the curve (AUC 0-∞) was 0.28 (0.24-0.31) on Day 11 and 0.26 (0.23-0.29) on Day 14. The AUC (0-12 hours) of CBZ was 114,000 ng∙h/mL on Day 11 and 105,000 ng∙h/mL on Day 14. Steady-state concentrations of CBZ and induction of CYP3A4 were achieved on Day 11. The data are consistent with predictions of physiologically-based pharmacokinetic models in Simcyp. The 9-day dosing regimen for CBZ induction was well-tolerated by healthy participants, supporting the use of a shorter CBZ regimen for CYP3A4 induction studies.

A brain metastasis liquid biopsy: Where are we now?

Brain metastases remain a challenging and feared complication for patients with cancer and research in this area has lagged behind research into metastases to other organs. Due to their location and the risks associated with neurosurgical biopsies, the biology underpinning brain metastases response to treatment and evolution over time remains poorly understood. Liquid biopsies are proposed to overcome many of the limitations present with tissue biopsies, providing a better representation of tumor heterogeneity, facilitating repeated sampling, and providing a noninvasive assessment of tumor biology. Several different liquid biopsy approaches have been investigated including circulating tumor cells, circulating tumor DNA, extracellular vesicles, and tumor-educated platelets; however, these have generally been less effective in assessing brain metastases compared to metastases to other organs requiring improved techniques to investigate these approaches, studies combining different liquid biopsy approaches and/or novel liquid biopsy approaches. Through this review, we highlight the current state of the art and define key unanswered questions related to brain metastases liquid biopsies.

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.

Metastatic Leptomeningeal Carcinomatosis From Primary Lobular Breast Cancer Found in a Medical School Cadaveric Dissection.

Leptomeningeal carcinomatosis (LC) is an uncommon sequelae of metastatic cancer affecting the pia and arachnoid mater. It has been postulated that recent improvements in cancer patient survival time have increased the frequency of LC and other rare metastatic conditions that patients previously would not have lived long enough to experience. LC carries a universally poor prognosis with a mean survival of between two to four months if treated; however, the recent increase in incidence has allowed for further research into the condition and potential treatments. Options for administering chemotherapy have been limited in the past, but recent developments in surgical chemotherapeutic ports have allowed for intrathecal delivery of drugs like methotrexate without systemic exposure. In fact, innovative delivery systems undergoing clinical trials can deliver these drugs in a metronomic fashion to limit the leukoencephalopathy complications of methotrexate. Primary breast cancer is the most common source of metastatic leptomeningeal lesions, and such a lesion was observed by the authors in the cadaver of a 70-year-old Caucasian female with unspecified breast cancer in a medical school anatomic laboratory. The cause of death was listed as "complication of malignant neoplasm of unspecified site of unspecified female breast." Through this case report, we seek to develop our understanding of this rare metastatic phenomenon and highlight the importance of student cadaveric dissection.

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.

Homogeneity in immune features between colorectal liver metastases better identifies patients with good prognosis compared to pathological response to preoperative chemotherapy.

In colorectal cancer liver metastases (CRLM), the density of tumor-infiltrating lymphocytes, the expression of class I major histocompatibility complex (MHC-I), and the pathological response to preoperative chemotherapy have been associated with oncological outcomes after complete resection. However, the prognostic significance of the heterogeneity of these features in patients with multiple CRLMs remains under investigation. We used a tissue microarray of 220 mismatch repair-gene proficient CRLMs resected in 97 patients followed prospectively to quantify CD3+ T cells and MHC-I by immunohistochemistry. Histopathological response to preoperative chemotherapy was assessed using standard scoring systems. We tested associations between clinical, immunological, and pathological features with oncologic outcomes. Overall, 29 patients (30.2%) had CRLMs homogeneous for CD3+ T cell infiltration and MHC-I. Patients with immune homogeneous compared to heterogeneous CRLMs had longer median time to recurrence (TTR) (30 vs. 12 months, p = .0018) and disease-specific survival (DSS) (not reached vs. 48 months, p = .0009). At 6 years, 80% of the patients with immune homogeneous CRLMs were still alive. Homogeneity of response to preoperative chemotherapy was seen in 60 (61.9%) and 69 (80.2%) patients according to different grading systems and was not associated with TTR or DSS. CD3 and MHC-I heterogeneity was independent of response to pre-operative chemotherapy and of other clinicopathological variables for their association with oncological outcomes. In patients with multiple CRLMs resected with curative intent, similar adaptive immune features seen across metastases could be more informative than pathological response to pre-operative chemotherapy in predicting oncological outcomes.

The relationship between physical characteristics and match collision performance among elite international female rugby union players.

This study investigated whether anthropometric and physical abilities explained variance in match collision performance among international female rugby union players. Physical performance and anthropometric data for fifty-one international female rugby union players, and collision actions categorised as "effort" or "performance" variables, from 20 international matches, were analysed using partial least squares regression. Among forwards, variance in carries/min was explained (R2 = .22) by a combination of; body mass, skinfolds, acceleration momentum and negative associations with mean aerobic speed and single-leg isometric squat relative force (SLISO/kgBM). Variance in collision dominance among forwards was explained (R2 = .21) by lower skinfolds and higher acceleration momentum, while tackles/min (R2 = .19) were explained by greater jumping power and single-leg isometric squat (SLISO). Among backs, variance in tackles/min (R2 = .54) was explained by greater bench press, SLISO and SLISO/kgBM. Variance in collision dominance among backs was explained (R2 = .23) by negative and positive associations with body mass and SLISO/kgBM, respectively. These findings suggest the development of physical characteristics, such as body mass and composition, strength and power contribute towards successful collision actions among international female rugby union players. The contribution of different physical characteristics towards collision events is dependent on position, and whether the collision event is categorised by "performance" or "effort". It is suggested that physical training programmes should reflect this level of specificity.HighlightsAmong elite female rugby union forwards, acceleration momentum, body mass and skinfolds are positively associated with winning collisions and carrying the ball into contact more frequently, whilst tackle frequency is positively associated with relative leg strength and power output.Among elite female backs, the ability to win collisions is positively associated with relative leg power output, and negatively associated with body mass. Tackle frequency is associated with maximum upper- and lower-body strength in this group.Physical characteristics account for some of the variability in collision performance, but interpretation of these findings should consider that factors such as technique during collision events may account for a larger proportion of total variance.Sports science practitioners can improve collision performance, to varying degrees, by enhancing specific gross physical characteristics, according to a player's position and the tactical role they are expected to fulfil.

Neurotensin neurons in the extended amygdala control dietary choice and energy homeostasis.

Obesity is a global pandemic that is causally linked to many life-threatening diseases. Apart from some rare genetic conditions, the biological drivers of overeating and reduced activity are unclear. Here, we show that neurotensin-expressing neurons in the mouse interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a nucleus of the central extended amygdala, encode dietary preference for unhealthy energy-dense foods. Optogenetic activation of IPACNts neurons promotes obesogenic behaviors, such as hedonic eating, and modulates food preference. Conversely, acute inhibition of IPACNts neurons reduces feeding and decreases hedonic eating. Chronic inactivation of IPACNts neurons recapitulates these effects, reduces preference for sweet, non-caloric tastants and, furthermore, enhances locomotion and energy expenditure; as a result, mice display long-term weight loss and improved metabolic health and are protected from obesity. Thus, the activity of a single neuronal population bidirectionally regulates energy homeostasis. Our findings could lead to new therapeutic strategies to prevent and treat obesity.

Small extracellular vesicle-associated miR-6068 promotes aggressive phenotypes of prostate cancer through miR-6068/HIC2/SIRT1 axis.

Early diagnosis and treatment of patients with aggressive prostate cancer (PCa) remains a clinically unmet need. We aimed to determine the levels of small extracellular vesicle (sEV)-associated microRNAs (miRs); miR-4737, miR-6068, and miR-6076 in a large panel of PCa cells and delineate the biological significance of miR-6068 in promoting PCa cells. sEVs were isolated from the conditioned medium of PCa cells, followed by RNA extraction and quantitative Real-Time PCR analysis. Functional assays were performed, and the protein expression of hypermethylated in cancer 2 (HIC2), as a potential miR-6068 target gene, was evaluated in PCa tissues by immunohistochemistry. sEV-associated miR-6068, miR-4737, and miR-6076 levels displayed large and significant differences compared to normal cells. miR-6068 was explicitly upregulated in sEV of PC-3 and CWR-R1ca cells (P<0.010). Suppression of miR-6068 in CWR-R1ca cells decreased cell proliferation, colony formation, and cell migration. In contrast, upregulation of miR-6068 in RC77T/E cells decreased HIC2 levels and increased cell aggressive phenotypes. The overexpression of HIC2 in PCa tissues was primarily observed in the cytoplasm compared to benign prostatic hyperplasia (BPH) and normal tissues (P<0.0001). This study confirms the differential packaging of miR-4737, miR-6068, and miR-6076 in sEVs of PCa cells. MiR-6068 promotes PCa cells to acquire aggressive phenotypes by inhibiting the HIC2/Sirtuin 1 (SIRT1) axis.

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.

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.

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.

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).

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.

Aerobic exercise with blood flow restriction causes local and systemic hypoalgesia and increases circulating opioid and endocannabinoid levels.

This study examined the effect of aerobic exercise with and without blood flow restriction (BFR) on exercise-induced hypoalgesia and endogenous opioid and endocannabinoid systems. In a randomized crossover design, pain-free individuals performed 20 min of cycling in four experimental trials: 1) low-intensity aerobic exercise (LI-AE) at 40% V̇o2max; 2) LI-AE with low-pressure BFR (BFR40); 3) LI-AE with high-pressure BFR (BFR80); and 4) high-intensity aerobic exercise (HI-AE) at 70% V̇o2max. Pressure pain thresholds (PPTs) were assessed before and 5 min postexercise. Circulating concentrations of beta-endorphin and 2-arachidonoylglycerol were assessed before and 10 min postexercise. In the exercising legs, postexercise PPTs were increased following BFR40 and BFR80 compared with LI-AE (23-32% vs. 1-2% increase, respectively). The increase in PPTs was comparable to HI-AE (17-20% increase) with BFR40 and greater with BFR80 (30-32% increase). Both BFR80 and HI-AE increased PPTs in remote areas of the body (increase of 26-28% vs. 19-21%, respectively). Postexercise circulating beta-endorphin concentration was increased following BFR40 (11%) and HI-AE (14%), with the greatest change observed following BFR80 (29%). Postexercise circulating 2-arachidonoylglycerol concentration was increased following BFR40 (22%) and BFR80 (20%), with the greatest change observed following HI-AE (57%). Addition of BFR to LI-AE can trigger both local and systemic hypoalgesia that is not observed follow LI-AE alone and activate endogenous opioid and endocannabinoid systems of pain inhibition. Compared with HI-AE, local and systemic hypoalgesia following LI-AE with high-pressure BFR is greater and comparable, respectively. LI-AE with BFR may help pain management in load-compromised individuals.NEW & NOTEWORTHY We have shown that performing blood flow restriction (BFR) during low-intensity aerobic exercise can trigger local and systemic hypoalgesia, which is not typically observed with this intensity of exercise. High-pressure BFR triggers greater and comparable hypoalgesia than high-intensity aerobic exercise in the exercising limbs and remote areas of the body, respectively. Performing BFR during low-intensity aerobic exercise activates the opioid and endocannabinoid systems, providing novel insight into potential mechanisms of hypoalgesia with BFR exercise.

Elite international female rugby union physical match demands: A five-year longitudinal analysis by position and opposition quality.

OBJECTIVES: This study aimed to evaluate changes in rugby union physical match characteristics across five seasons of International female competition, according to position and opposition quality. DESIGN & METHODS: Global positional systems and performance analysis data from 78 female rugby union players (minimum of five international appearances) were analysed between 2015 and 2019. Mixed-linear-modelling was used to investigate the effects of season, opposition and position during 969 individual match performances from 53 International matches. RESULTS: Running demands increased between 2015 and 2017 (World Cup year) and plateaued thereafter, except for sprints among the outside backs, which declined between 2017 and 2019, and accelerations and decelerations >3 m s2 which increased between 2017 and 2019. Collisions were higher in forwards than backs, and highest against stronger opposition. Running demands were greater against weaker opposition, but the 'most intense periods' of running were greater against stronger opposition in 2017. CONCLUSIONS: Match demands increased between 2015 and the 2017 World Cup year, which was underpinned by increased sprinting and greater running during maximum intensity periods against top 5 opposition. The increase in accelerations and decelerations in the latter years, alongside the maintenance of average running demands and collision counts, is consistent with the reported continuous playing style of female rugby, thus placing specific demands on players and requiring tailored training methods. Some positions (Forwards and Scrum-halves) appear to be important for this adopted style, demonstrating concomitantly high relative collision and running intensities.