Optimal Beam Polarizations for New-Physics Search through gamma gamma -> t tbar -> lX/bX

We perform an optimal-observable analysis of the final charged-lepton/b-quark momentum distributions in gamma+gamma -> t+tbar -> lX/bX for various beam polarizations in order to study possible anomalous t-tbar-gamma, tbW and gamma-gamma-H couplings, which could be generated by SU(2)xU(1) gauge-invariant dimension-6 effective operators. We find optimal beam polarizations that will minimize the uncertainty in determination of those non-standard couplings. We also compare e+ebar and gamma+gamma colliders from the viewpoint of the anomalous-top-quark-coupling determination.Comment: Final version, published in JHEP : more detailed description of the basic framework given with some new references, and three related appendices adde

Baseline Psychological Traits Contribute to Lake Louise Acute Mountain Sickness Score at High Altitude

Talks, Benjamin James, Catherine Campbell, Stephanie J. Larcombe, Lucy Marlow, Sarah L. Finnegan, Christopher T. Lewis, Samuel J.E. Lucas, Olivia K. Harrison, and Kyle T.S. Pattinson. Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude. High Alt Med Biol. 23:69-77, 2022. Background: Interoception refers to an individual's ability to sense their internal bodily sensations. Acute mountain sickness (AMS) is a common feature of ascent to high altitude that is only partially explained by measures of peripheral physiology. We hypothesized that interoceptive ability may explain the disconnect between measures of physiology and symptom experience in AMS. Methods: Two groups of 18 participants were recruited to complete a respiratory interoceptive task three times at 2-week intervals. The control group remained in Birmingham (140 m altitude) for all three tests. The altitude group completed test 1 in Birmingham, test 2 the day after arrival at 2,624 m, and test 3 at 2,728 m after an 11-day trek at high altitude (up to 4,800 m). Results: By measuring changes to metacognitive performance, we showed that acute ascent to altitude neither presented an interoceptive challenge, nor acted as interoceptive training. However, AMS symptom burden throughout the trek was found to relate to sea level measures of anxiety, agoraphobia, and neuroticism. Conclusions: This suggests that the Lake Louise AMS score is not solely a reflection of physiological changes on ascent to high altitude, despite often being used as such by researchers and commercial trekking companies alike. Keywords: acute mountain sickness; altitude; breathlessness; exercise; filter detection task; interoceptio

Expert United Kingdom consensus on the preservation of joint health in people with moderate and severe haemophilia A: A modified Delphi panel

Aim: For people with haemophilia A (PwHA), bleeding in the joints leads to joint damage and haemophilia-related arthropathy, impacting range of motion and life expectancy. Existing guidelines for managing haemophilia A support healthcare professionals (HCPs) and PwHA in their efforts to preserve joint health. However, such guidance should be reviewed, considering emerging evidence and consensus as presented in this manuscript. Methods: Fifteen HCPs experienced in the management of PwHA in the UK participated in a three-round Delphi panel. Consensus was defined at ≥70% of panellists agreeing or disagreeing for Likert-scale questions, and ≥70% selecting the same option for multiple- or single-choice questions. Questions not reaching consensus were revised for the next round. Results: 26.8% (11/41), 44.8% (13/29) and 93.3% (14/15) of statements reached consensus in Rounds 1, 2 and 3, respectively. HCPs agreed that prophylaxis should be offered to patients with a baseline factor VIII (FVIII) level of ≤5 IU/dL and that, where there is no treatment burden, the aim of prophylaxis should be to achieve a trough FVIII level ≥15 IU/dL and maintain a longer period with FVIII levels of ≥20-30 IU/dL to provide better bleed protection. The aspirational goal for PwHA is to prevent all joint bleeds, which may be achieved by maintaining normalised (50-150 IU/dL) FVIII levels. Conclusion: The panel of experts were largely aligned on approaches to preserving joint health in PwHA, and this consensus may help guide HCPs

ALPGEN, a generator for hard multiparton processes in hadronic collisions

This paper presents a new event generator, ALPGEN, dedicated to the study of multiparton hard processes in hadronic collisions. The code performs, at the leading order in QCD and EW interactions, the calculation of the exact matrix elements for a large set of parton-level processes of interest in the study of the Tevatron and LHC data. The current version of the code describes the following final states: (W -> ffbar') QQbar+ N jets (Q being a heavy quark, and f=l,q), with N f fbar)+QQbar+Njets (f=l,nu), with N ffbar') + charm + N jets (f=l,q), N f fbar') + N jets (f=l,q) and (Z/gamma* -> f fbar)+ N jets (f=l,nu), with N<=6; nW+mZ+lH+N jets, with n+m+l+N<=8 and N<=3 including all 2-fermion decay modes of W and Z bosons, with spin correlations; Q Qbar+N jets (N b f fbar' decays and relative spin correlations included if Q=t; Q Qbar Q' Qbar'+N jets, with Q and Q' heavy quarks (possibly equal) and N b f fbar' decays and relative spin correlations included if Q=t; N jets, with N<=6. Parton-level events are generated, providing full information on their colour and flavour structure, enabling the evolution of the partons into fully hadronised final states.Comment: 1+38 pages, uses JHEP.cls. Documents code version 1.2: extended list of processes, updated documentation and bibliograph

Expert United Kingdom consensus on the preservation of joint health in people with moderate and severe haemophilia A: A modified Delphi panel

\ua9 2024 The Authors. Haemophilia published by John Wiley &amp; Sons Ltd.Aim: For people with haemophilia A (PwHA), bleeding in the joints leads to joint damage and haemophilia-related arthropathy, impacting range of motion and life expectancy. Existing guidelines for managing haemophilia A support healthcare professionals (HCPs) and PwHA in their efforts to preserve joint health. However, such guidance should be reviewed, considering emerging evidence and consensus as presented in this manuscript. Methods: Fifteen HCPs experienced in the management of PwHA in the UK participated in a three-round Delphi panel. Consensus was defined at ≥70% of panellists agreeing or disagreeing for Likert-scale questions, and ≥70% selecting the same option for multiple- or single-choice questions. Questions not reaching consensus were revised for the next round. Results: 26.8% (11/41), 44.8% (13/29) and 93.3% (14/15) of statements reached consensus in Rounds 1, 2 and 3, respectively. HCPs agreed that prophylaxis should be offered to patients with a baseline factor VIII (FVIII) level of ≤5 IU/dL and that, where there is no treatment burden, the aim of prophylaxis should be to achieve a trough FVIII level ≥15 IU/dL and maintain a longer period with FVIII levels of ≥20–30 IU/dL to provide better bleed protection. The aspirational goal for PwHA is to prevent all joint bleeds, which may be achieved by maintaining normalised (50–150 IU/dL) FVIII levels. Conclusion: The panel of experts were largely aligned on approaches to preserving joint health in PwHA, and this consensus may help guide HCPs

BMC Ophthalmol

Background Systematically review the evidence describing the impact of anti–vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization. Methods A systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches. Results The use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients’ VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently administered treatments (e.g. photodynamic therapy) and increased number of patients treated (prior to anti-VEGF, only ~ 20% of patients were eligible for treatment). Conclusions The introduction of anti-VEGF agents has been associated with a positive impact on patient-relevant outcomes, including a significant reduction in incidence of blindness and visual impairment by nAMD. Anti-VEGF agents replaced less-effective treatments, improving patient outcomes and broadening the patient population eligible for treatment

The ANZUS Treaty during the Cold War: a reinterpretation of U.S. diplomacy in the Southwest Pacific

This article explains the origins of the Australia–New Zealand–United States (ANZUS) Treaty by highlighting U.S. ambitions in the Pacific region after World War II. Three clarifications to the historiography merit attention. First, an alliance with Australia and New Zealand reflected the pursuit of U.S. interests rather than the skill of antipodean diplomacy. Despite initial reservations in Washington, geostrategic anxiety and economic ambition ultimately spurred cooperation. The U.S. government's eventual recourse to coercive diplomacy against the other ANZUS members, and the exclusion of Britain from the alliance, substantiate claims of self-interest. Second, the historiography neglects the economic rationale underlying the U.S. commitment to Pacific security. Regional cooperation ensured the revival of Japan, the avoidance of discriminatory trade policies, and the stability of the Bretton Woods monetary system. Third, scholars have unduly played down and misunderstood the concept of race. U.S. foreign policy elites invoked ideas about a “White Man's Club” in Asia to obscure the pursuit of U.S. interests in the region and to ensure British exclusion from the treaty

Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo

Multiple myeloma is a B cell malignancy. Recently, it has been demonstrated that bone marrow samples of patients with multiple myeloma display an enhanced angiogenesis. The mechanisms involved seem to be multiple and complex. We here demonstrate that the murine 5T multiple myeloma models are able to induce angiogenesis in vitro by using a rat aortic ring assay and in vivo by determining the microvessel density. The rat aortic rings cultured in 5T multiple myeloma conditioned medium exhibit a higher number of longer and more branched microvessels than the rings cultured in control medium. In bone marrow samples from 5T multiple myeloma diseased mice, a statistically significant increase of the microvessel density was observed when compared to bone marrow samples from age-matched controls. The angiogenic phenotype of both 5T multiple myeloma cells could be related, at least in part, to their capacity to produce vascular endothelial growth factor. These data clearly demonstrate that the 5T multiple myeloma models are good models to study angiogenesis in multiple myeloma and will allow to unravel the mechanisms of neovascularisation, as well as to test new putative inhibitors of angiogenesis

Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

Hypoxia inducible factors HIF1α and HIF2α are important proteins involved in the regulation of the transcription of a variety of genes related to erythropoiesis, glycolysis and angiogenesis. Hypoxic stimulation results in rapid increase of the HIF1α and 2α protein levels, as a consequence of a redox-sensitive stabilization. The HIFαs enter the nucleus, heterodimerize with the HIF1β protein, and bind to DNA at the hypoxia response elements (HREs) of target genes. In this study we evaluated the immunohistochemical expression of these proteins in 108 tissue samples from non-small-cell lung cancer (NSCLC) and in normal lung tissues. Both proteins showed a mixed cytoplasmic/nuclear pattern of expression in cancer cells, tumoural vessels and tumour-infiltrating macrophages, as well as in areas of metaplasia, while normal lung components showed negative or very weak cytoplasmic staining. Positive HIF1α and HIF2α expression was noted in 68/108 (62%) and in 54/108 (50%) of cases respectively. Correlation analysis of HIF2α expression with HIF1α expression showed a significant association (P < 0.0001, r = 0.44). A strong association of the expression of both proteins with the angiogenic factors VEGF (P < 0.004), PD-ECGF (P < 0.003) and bFGF (P < 0.04) was noted. HIF1α correlated with the expression of bek-bFGF receptor expression (P = 0.01), while HIF2α was associated with intense VEGF/KDR-activated vascularization (P = 0.002). HIF2α protein was less frequently expressed in cases with a medium microvessel density (MVD); a high rate of expression was noted in cases with both low and high MVD (P = 0.006). Analysis of overall survival showed that HIF2α expression was related to poor outcome (P = 0.008), even in the group of patients with low MVD (P = 0.009). HIF1α expression was marginally associated with poor prognosis (P = 0.08). In multivariate analysis HIF2α expression was an independent prognostic indicator (P = 0.006, t-ratio 2.7). We conclude that HIF1α and HIF2α overexpression is a common event in NSCLC, which is related to the up-regulation of various angiogenic factors and with poor prognosis. Targeting the HIF pathway may prove of importance in the treatment of NSCLC. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee

Emicizumab is a bispecific antibody that activates FX to FXa in the absence of FVIII. It has been shown to reduce bleeding episodes in people with haemophilia A complicated by a FVIII inhibitor. Despite the protection against bleeds, some breakthrough bleeds are inevitable and these may require additional haemostatic treatment. Emicizumab has been associated with severe adverse events when co‐administered with activated prothrombin complex concentrate. To minimize the risk of adverse events, the UK Haemophilia Centre Doctors’ Organisation issues the following updated interim guidance to its Inhibitor Guidelines for managing patients receiving Emicizumab based on the limit published information available in February 2018