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1. The Solar and Geomagnetic Storms in May 2024: A Flash Data Report

Author

Hayakawa, Hisashi, Ebihara, Yusuke, Mishev, Alexander, Koldobskiy, Sergey, Kusano, Kanya, Bechet, Sabrina, Yashiro, Seiji, Iwai, Kazumasa, Shinbori, Atsuki, Mursula, Kalevi, Miyake, Fusa, Shiota, Daikou, Silveira, Marcos V. D., Stuart, Robert, Oliveira, Denny M., Akiyama, Sachiko, Ohnishi, Kouji, and Miyoshi, Yoshizumi

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Earth and Planetary Astrophysics, Physics - Space Physics
Abstract

In May 2024, the scientific community observed intense solar eruptions that resulted in an extreme geomagnetic storm and auroral extension, highlighting the need to document and quantify these events. This study mainly focuses on their quantification. The source active region (AR 13664) evolved from 113 to 2761 millionths of the solar hemisphere between 4 May and 14 May 2024. AR 13664's magnetic free energy surpassed 1033 erg on 7 May 2024, triggering 12 X-class flares. Multiple interplanetary coronal mass ejections (ICMEs) came out from this AR, accelerating solar energetic particles toward Earth. At least four ICMEs seemingly piled up to disturb the interplanetary space, according to the satellite data and interplanetary scintillation data. The shock arrival at 17:05 UT on 10 May 2024 significantly compressed the magnetosphere down to ~ 5.04 R_E, and triggered a deep Forbush decrease. GOES satellite data and ground-based neutron monitors confirmed a ground-level enhancement from 2 UT to 10 UT on 11 May 2024. The ICMEs induced extreme geomagnetic storms, peaking at a Dst index of -412 nT at 2 UT on 11 May 2024, marking the sixth-largest storm since 1957. The AE and AL indices showed extreme auroral extensions that located the AE/AL stations into the polar cap. We gathered auroral records at that time and reconstructed the equatorward boundary of the visual auroral oval to 29.8{\deg} invariant latitude. We compared naked-eye and camera auroral visibility, providing critical caveats on their difference. We also confirmed global enhancements of storm-enhanced density of the ionosphere., Comment: 39 pages, 20 figures, and 2 tables. Figures 15 and 17 will appear on the record version. Under Review

Published
2024

2. The Profiles of Bars in Spiral Galaxies

Author

Erwin, Peter, Debattista, Victor P., and Anderson, Stuart Robert

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

We present an analysis of major-axis surface-brightness profiles of bars in a volume-limited sample of 182 barred spiral galaxies, using Spitzer 3.6 micron images. Unlike most previous studies, we use the entire bar profile, and we classify profiles into four categories. These are "Peak+Shoulders" (P+Sh) -- updating the classic "flat bar" profile -- and three subtypes of the classic "exponential" profile: (true) Exponential, "Two-Slope" (shallow inner slope + steeper outer slope), and "Flat-Top" (constant inner region, steep outer slope). P+Sh profiles are preferentially found in galaxies with high stellar masses, early Hubble types, red colours, and low gas fractions; the most significant factor is stellar mass, and previous correlations with Hubble type can be explained by the tendency of higher-mass galaxies to have earlier Hubble types. The most common type of non-P+Sh profile is Exponential, followed by Flat-Top profiles; all non-P+Sh profiles appear to have similar distributions of stellar mass, Hubble type, colour, and gas fraction. We also morphologically classify the bars of an inclined subsample into those with and without boxy/peanut-shaped (B/P) bulges; as previously reported, the presence of a B/P bulge is very strong function of stellar mass. Essentially all bars with B/P bulges have P+Sh profiles; we associate the profile shoulders with the outer, vertically thin part of the bar. We find a small number of P+Sh profiles in bars without clear B/P bulges, which may indicate that P+Sh formation precedes the formation of B/P bulges., Comment: pdflatex, 21 pages, 12 figures; accepted by MNRAS. Data, code, and Jupyter notebooks available at https://github.com/perwin/barprofiles_paper

Published
2023
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3. The interplay between accretion, galaxy downsizing and the formation of box/peanut bulges in TNG50

Author

Anderson, Stuart Robert, Gough-Kelly, Steven, Debattista, Victor P., Du, Min, Erwin, Peter, Cuomo, Virginia, Caruana, Joseph, Hernquist, Lars, and Vogelsberger, Mark

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

From the TNG50 cosmological simulation we build a sample of 191 well-resolved barred galaxies with a stellar mass $\logMstar > 10$ at $z=0$. We search for box/peanut bulges (BPs) in this sample, finding them in 55\% of cases. We compute $\fbp$, the BP probability for barred galaxies as a function of $\Mstar$, and find that this rises to a plateau, as found in observations of nearby galaxies. The transition mass where $\fbp$ reaches half the plateau value is $\logMstar = 10.14$, consistent with the observational value within measurement errors. We show that this transition in $\fbp$ can be attributed to the youth of the bars at low $\Mstar$, which is a consequence of downsizing of galaxies. Young bars, being generally shorter and weaker, have not yet had time to form BPs. At high mass, while we find a plateau, the value is at $\sim 60\%$ whereas observations saturate at $100\%$. We attribute this difference to excessive heating in TNG50, due to merger activity and to numerical resolution effects. BPs in TNG50 tend to occur in galaxies with more quiescent merger histories. As a result, the main driver of whether a bar hosts a BP in TNG50 is not the galaxy mass, but how long and strong the bar is. Separating the BP sample into those that have visibly buckled and those that have not, we find that fully half of BP galaxies show clear signs of buckling, despite the excessive heating and limited vertical resolution of TNG50., Comment: 20 pages, 24 figures, 5 tables. Submitted to MNRAS

Published
2023

5. Protocol for the RoboSling Trial: A Randomised Study Assessing Urinary Continence Following Robotic Radical Prostatectomy with or without an Intraoperative Retropubic Vascularised Fascial Sling (RoboSling)

Author

Amandeep Virk, Patrick-Julien Treacy, Wenjie Zhong, Stuart Robert Jackson, Nariman Ahmadi, Nicola Nadia Jeffery, Lewis Chan, Paul Sved, Arthur Vasilaras, Ruban Thanigasalam, and Scott Leslie

Subjects
incontinence, intraoperative sling, prostate cancer, prostatectomy, robotic surgery, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Objectives: To determine if early (three months) and late (one year) post-operative continence is improved by performing a novel retropubic vascularised fascial sling (RoboSling) procedure concurrently with robot-assisted radical prostatectomy in men undergoing treatment for localised prostate cancer. To additionally assess surgical outcomes, quality of life and health economic outcomes in patients undergoing the novel RoboSling technique. Methods: This study aims to recruit 120 consecutive patients with clinically localised prostate cancer who have chosen to undergo robot-assisted radical prostatectomy in the Sydney Local Health District, Australia. A prospective assessment of early and late post-operative continence following robot-assisted radical prostatectomy with and without a RoboSling procedure will be performed in a two-group, 1:1, parallel, randomized controlled trial. Four surgeons will take part in the study, all of whom are beyond their learning curve. Patients will be blinded as to whether the RoboSling procedure is performed for them, as will be the research officers collecting the post-operative data on urinary function. Trial Registration: ACTRN12618002058257. Results: The trial is currently underway. Conclusions: The RoboSling technique is unique in that the sling is vascularised and has a broad surface area compared to previously described slings in the literature. If a clinically significant improvement in post-operative continence is established with the RoboSling, then, we can in turn expect improvements in quality of life for men undergoing this technique with radical prostatectomy.

Published
2024
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6. The secular growth of bars revealed by flat (peak + shoulders) density profiles

Author

Anderson, Stuart Robert, Debattista, Victor P., Erwin, Peter, Liddicott, David J., Deg, Nathan, and Silva, Leandro Beraldo e

Subjects
Astrophysics - Astrophysics of Galaxies
Abstract

The major-axis density profiles of bars are known to be either exponential or 'flat'. We develop an automated non-parametric algorithm to detect flat profiles and apply it to a suite of simulations (with and without gas). We demonstrate that flat profiles are a manifestation of a bar's secular growth, producing a 'shoulder' region (an overdensity above an exponential) in its outskirts. Shoulders are not present when bars form, but develop as the bar grows. If the bar does not grow, shoulders do not form. Shoulders are often accompanied by box/peanut bulges, but develop separately from them and are independent tracers of a bar's growth. They can be observed at a wide range of viewing orientations with only their slope varying significantly with inclination. We present evidence that shoulders are produced by looped x1 orbits. Since the growth rate of the bar moderately correlates with the growth rate of the shoulder strength, these orbits are probably recently trapped. Shoulders therefore are evidence of bar growth. The properties of the shoulders do not, however, establish the age of a bar, because secondary buckling or strong spirals may destroy shoulders, and also because shoulders do not form if the bar does not grow much. In particular, our results show that an exponential profile is not necessarily an indication of a young bar., Comment: 20 pages, 23 figures, 2 tables. Published in MNRAS

Published
2022
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7. Money, credit and regional development : complementary local currencies and the provision of small business credit

Author

Bowles, Stuart Robert

Subjects
G Geography (General)
Abstract

The aim of this investigation is to understand the contribution complementary local currencies can have on regional sustainable development through the provision of credit to small businesses. Complementary local currencies have been studied by researchers for nearly forty years. The literature identifies an implicit relationship between these schemes and regional sustainable development, even though recent research suggests that contributions are limited. More recently there has been a recognition within this field, alongside wider academic and policy maker discourse, that small businesses play an important role in developing a sustainable local economy. This thesis first considers money and credit on an ontological level, which allows a deeper theoretical understanding of what money is as a core concept. It draws on heterodox economic scholars that highlight "credit, and credit alone, is money" (Innes, 1914: 159). With this basis it is able to critically analyse complementary local currencies, identifying a dichotomy between schemes that apply a commodity and a credit understanding of money. This crucial difference is often overlooked by academics and practitioners, however it appears to have a significant impact on the ability of complementary local currencies to operate and scale up. These insights are used to consider how credit-based complementary local currencies can be used to support regional sustainable development through the provision of credit to small businesses. Empirically, half of the study is dedicated to an under-researched complementary local currency called Sardex, based in Sardinia, Italy. The research applies heterodox understandings of money and credit to understand why this scheme has been so successful. It then considers the initial contributions that Sardex has to regional sustainable development. It identifies positive initiatives that demonstrate that a functioning credit-based complementary local currency can meet a series of policy objectives. The second part of the study turns to schemes in the UK. It first considers the dominant models used in practice, which are largely Convertible Local Currencies, like the Bristol Pound, and locally applied cryptocurrencies, similar to Bitcoin. These models apply a commodity-based understanding of money, which this thesis argues limits their ability to develop a financially sustainable business model or make a significant contribution to regional sustainable development. The thesis considers where credit-based complementary local currencies have been applied by schemes, but have largely failed to start. It draws on Commercial Barter Networks, which are ignored by local currency academics and practitioners, to provide more insights into this credit-based model. Finally, the insights from the first three chapters are used to support the development of a credit-based complementary local currency in Birmingham. Ethnographic techniques are used to detail insights made from direct involvement in starting this scheme. The contribution of this research centres on the ability to understand money and credit on an ontological basis. The recognition that money within the dominant economy is credit-based, provides a starting point for the development of more effective complementary local currencies, including their ability to meet regional sustainable development objectives. The research provides theoretical insights alongside practical suggestions for policy makers and complementary local currency schemes. The aim is to support the sharing of the good practice identified within Sardex that is operating a financially sustainable complementary local currency and making contributions to a series of regional sustainable development objectives.

Published
2022

9. Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma.

Author

Chari, Ajai, Cornell, Robert, Gasparetto, Cristina, Karanes, Chatchada, Matous, Jeffrey, Niesvizky, Ruben, Lunning, Matthew, Usmani, Saad, Anderson, Larry, Chhabra, Saurabh, Girnius, Saulius, Shustik, Chaim, Stuart, Robert, Lee, Yihua, Salman, Zeena, Liu, Emily, and Valent, Jason

Subjects
Brutons tyrosine kinase inhibitor, carfilzomib, ibrutinib, multiple myeloma, Adenine, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Drug Resistance, Neoplasm, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multiple Myeloma, Neoplasm Recurrence, Local, Oligopeptides, Piperidines, Prognosis, Pyrazoles, Pyrimidines, Salvage Therapy, Survival Rate
Abstract

Patients with multiple myeloma (MM) inevitably relapse on initial treatment regimens, and novel combination therapies are needed. Ibrutinib is a first-in-class, once-daily inhibitor of Brutons tyrosine kinase, an enzyme implicated in growth and survival of MM cells. Preclinical data suggest supra-additivity or synergy between ibrutinib and proteasome inhibitors (PIs) against MM. This phase 1/2b study evaluated the efficacy and safety of ibrutinib plus the PI carfilzomib and dexamethasone in patients with relapsed/refractory MM (RRMM). In this final analysis, we report results in patients who received the recommended phase 2 dose (RP2D; ibrutinib 840 mg and carfilzomib 36 mg/m2 with dexamethasone), which was determined in phase 1. The primary efficacy endpoint was overall response rate (ORR). Fifty-nine patients with RRMM received the RP2D (18 in phase 1 and 41 in phase 2b). These patients had received a median of three prior lines of therapy; 69% were refractory to bortezomib, and 90% were refractory to their last treatment. ORR in the RP2D population was 71% (stringent complete response and complete response: 3% each). Median duration of clinical benefit and median duration of response were both 6.5 months. Median progression-free survival (PFS) was 7.4 months, and median overall survival (OS) was 35.9 months. High-risk patients had comparable ORR and median PFS (67% and 7.7 months, respectively) to non-high-risk patients, whose ORR was 73% and median PFS was 6.9 months, whereas median OS in high-risk patients was 13.9 months and not reached in non-high-risk patients. The most common grade ≥3 hematologic treatment-emergent adverse events (TEAEs) were anemia and thrombocytopenia (17% each); the most common grade ≥3 non-hematologic TEAE was hypertension (19%). In patients with RRMM treated with multiple previous lines of therapy, ibrutinib plus carfilzomib demonstrated anticancer activity within the expected efficacy range. No new safety signals were identified and the combination was well-tolerated.

Published
2020

10. What drives black hole and galaxy growth in the EAGLE simulation?

Author

McAlpine, Stuart Robert

Subjects
530
Abstract

In this thesis we investigate what drives the evolution of actively accreting central supermassive black holes and unusually active strongly star-forming galaxies using the Evolution and Assembly of GaLaxies and their Environments (EAGLE) suite of cosmological hydrodynamical simulations. We find that many of our results are intimately tied to the complex evolutionary pathway taken by the central black holes within the simulation. This evolution can be separated into three distinct phases, each related to the mass of the host dark matter halo. In low mass haloes, stellar feedback dominates by driving an effective outflow and substantially hinders the growth of the central black hole. As haloes become more massive, the stellar feedback loses its efficiency, and the outflow stalls. This gives the first opportunity for the central black hole to grow, which is does so initially at a rapid rate. After this phase of rapid growth, the central black hole then becomes sufficiently massive to regulate the gas inflow onto the halo, resulting in both the star formation of the galaxy and any continued rapid growth of the central black hole to be substantially restricted via the outputted energy of an actively accreting supermassive black hole (referred to as an active galactic nuclei, or AGN). In Chapter 2 we discover that this complex evolutionary behaviour is integral to understanding how the growth rates of galaxies and their black holes are related to each other throughout cosmic time. We use this behaviour to explain why the current observational studies report different relationships between galaxy and black hole growth rates depending on the initial selection method used. Finally, in Chapter 3 we find that the evolutionary state of the black hole is also closely connected with high star formation rates in lower mass galaxies ($M_* \lesssim 10^{11}$~\Msol, where $M_*$ is the stellar mass of the galaxy). Such 'starbursting' galaxies are rare, and we argue that they are produced through a culmination of two coinciding events; (1) the galaxy must host an underdeveloped black hole (one that has not yet entered its rapid growth phase), thus ensuring that the galaxy has maintained a gas rich reservoir and contains a low mass black hole; and (2) the galaxy must undergo an interaction to kick-start the starburst process. This tells us that strongly star-forming galaxies are a predominately merger driven population that host undermassive black holes, making them fundamentally distinct from the 'typical' star-forming population.

Published
2018

11. CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia

Author

Lancet, Jeffrey E, Uy, Geoffrey L, Cortes, Jorge E, Newell, Laura F, Lin, Tara L, Ritchie, Ellen K, Stuart, Robert K, Strickland, Stephen A, Hogge, Donna, Solomon, Scott R, Stone, Richard M, Bixby, Dale L, Kolitz, Jonathan E, Schiller, Gary J, Wieduwilt, Matthew J, Ryan, Daniel H, Hoering, Antje, Banerjee, Kamalika, Chiarella, Michael, Louie, Arthur C, and Medeiros, Bruno C

Subjects
Orphan Drug, Clinical Trials and Supportive Activities, Hematology, Pediatric, Cancer, Rare Diseases, Clinical Research, Pediatric Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Aged, Antineoplastic Combined Chemotherapy Protocols, Cytarabine, Daunorubicin, Female, Humans, Leukemia, Myeloid, Acute, Male, Middle Aged, Neoplasms, Second Primary, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen. The primary end point was overall survival. Results CPX-351 significantly improved median overall survival versus 7+3 (9.56 v 5.95 months; hazard ratio, 0.69; 95% CI, 0.52 to 0.90; one-sided P = .003). Overall remission rate was also significantly higher with CPX-351 versus 7+3 (47.7% v 33.3%; two-sided P = .016). Improved outcomes were observed across age-groups and AML subtypes. The incidences of nonhematologic adverse events were comparable between arms, despite a longer treatment phase and prolonged time to neutrophil and platelet count recovery with CPX-351. Early mortality rates with CPX-351 and 7+3 were 5.9% and 10.6% (two-sided P = .149) through day 30 and 13.7% and 21.2% (two-sided P = .097) through day 60. Conclusion CPX-351 treatment is associated with significantly longer survival compared with conventional 7+3 in older adults with newly diagnosed sAML. The safety profile of CPX-351 was similar to that of conventional 7+3 therapy.

Published
2018

12. Comparative Life Cycle Assessment of tidal stream turbine blades

Author

Stuart Robert John Walker, Philipp R Thies, and Lars Johanning

Subjects
Tidal turbine blades, Life cycle assessment, Enviromental impact assessment, Carbon footprint, Ocean engineering, TC1501-1800, Renewable energy sources, TJ807-830
Abstract

Renewable energy allows electricity generation with lower environmental and resource impact than generation from fossil fuels. However, the manufacture, use and ultimate disposal of the equipment used to capture this energy has an environmental impact, which should be minimised. Tidal turbine blades are currently primarily manufactured from glass-fibre reinforced polymers. Such blades cannot be recycled at the end of their life, and are disposed of in landfill or by incineration. As the tidal energy industry grows, the volume of non-recyclable waste is a potential problem. Here we consider the environmental impact of ten combinations of material and disposal method for tidal stream turbine blades, including recyclable options. Our findings suggest that glass fibre blades have greenhouse gas emissions of around 15,500 kgCO2e for the scope considered, and a significant environmental impact in all impact categories, which would be increased by changing to carbon fibre (99% mean increase from glass fibre across impact categories) or steel (134% mean increase from glass fibre across impact categories) blades, but that composite materials using flax fibre and recyclable resin may have lower impact (26% mean decrease from glass fibre across impact categories), provided they are treated correctly after use. These materials may also offer the potential for lower cost blades in future.

Published
2022
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13. Protocol for the RoboSling Trial: A Randomised Study Assessing Urinary Continence Following Robotic Radical Prostatectomy with or without an Intraoperative Retropubic Vascularised Fascial Sling (RoboSling)

Author

Virk, Amandeep, primary, Treacy, Patrick-Julien, additional, Zhong, Wenjie, additional, Jackson, Stuart Robert, additional, Ahmadi, Nariman, additional, Jeffery, Nicola Nadia, additional, Chan, Lewis, additional, Sved, Paul, additional, Vasilaras, Arthur, additional, Thanigasalam, Ruban, additional, and Leslie, Scott, additional

Published
2024
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14. Autologous and allogeneic hematopoietic cell transplantation for diffuse large B-cell lymphoma–type Richter syndrome

Author

Herrera, Alex F., Ahn, Kwang Woo, Litovich, Carlos, Chen, Yue, Assal, Amer, Bashir, Qaiser, Bayer, Ruthee-Lu, Coleman, Melanie, DeFilipp, Zachariah, Farhadfar, Nosha, Greenwood, Matthew, Hahn, Theresa, Horwitz, Mitchell, Jacobson, Caron, Jaglowski, Samantha, Lachance, Sylvie, Langston, Amelia, Mattar, Bassam, Maziarz, Richard T., McGuirk, Joseph, Mian, Mohammad A.H., Nathan, Sunita, Phillips, Adrienne, Rakszawski, Kevin, Sengeloev, Henrik, Shenoy, Shalini, Stuart, Robert, Sauter, Craig S., Kharfan-Dabaja, Mohamed A., and Hamadani, Mehdi

Published
2021
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15. Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance)

Author

Walker, Alison R., Marcucci, Guido, Yin, Jun, Blum, William, Stock, Wendy, Kohlschmidt, Jessica, Mrózek, Krzysztof, Carroll, Andrew J., Eisfeld, Ann-Kathrin, Wang, Eunice S., Jacobson, Sawyer, Kolitz, Jonathan E., Thakuri, Mohan, Sutamtewagul, Grerk, Vij, Ravi, Stuart, Robert K., Byrd, John C., Bloomfield, Clara D., Stone, Richard M., and Larson, Richard A.

Published
2021
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16. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1–2 study

Author

Perl, Alexander E, Altman, Jessica K, Cortes, Jorge, Smith, Catherine, Litzow, Mark, Baer, Maria R, Claxton, David, Erba, Harry P, Gill, Stan, Goldberg, Stuart, Jurcic, Joseph G, Larson, Richard A, Liu, Chaofeng, Ritchie, Ellen, Schiller, Gary, Spira, Alexander I, Strickland, Stephen A, Tibes, Raoul, Ustun, Celalettin, Wang, Eunice S, Stuart, Robert, Röllig, Christoph, Neubauer, Andreas, Martinelli, Giovanni, Bahceci, Erkut, and Levis, Mark

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Rare Diseases, Clinical Trials and Supportive Activities, Patient Safety, Lung, Clinical Research, Cancer, Infectious Diseases, Genetics, Hematology, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aged, Aniline Compounds, Antineoplastic Agents, Blood Platelets, Female, Humans, Leukemia, Myeloid, Acute, Male, Maximum Tolerated Dose, Middle Aged, Phosphorylation, Pyrazines, Recurrence, Retreatment, fms-Like Tyrosine Kinase 3, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro.

Published
2017

17. Reassessment of Rebleeding Risk of Forrest IB (Oozing) Peptic Ulcer Bleeding in a Large International Randomized Trial

Author

Jensen, Dennis M, Eklund, Stefan, Persson, Tore, Ahlbom, Henrik, Stuart, Robert, Barkun, Alan N, Kuipers, Ernest J, Mössner, Joachim, Lau, James Y, Sung, Joseph J, Kilhamn, Jan, and Lind, Tore

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Administration, Intravenous, Aged, Double-Blind Method, Electrocoagulation, Endoscopy, Digestive System, Epinephrine, Esomeprazole, Female, Hemostasis, Surgical, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Peptic Ulcer, Peptic Ulcer Hemorrhage, Proton Pump Inhibitors, Randomized Controlled Trials as Topic, Recurrence, Risk Assessment, Surgical Instruments, Treatment Outcome, Vasoconstrictor Agents, Gastroenterology & Hepatology, Clinical sciences
Abstract

ObjectivesOur aims were to assess risks of early rebleeding after successful endoscopic hemostasis for Forrest oozing (FIB) peptic ulcer bleeding (PUBs) compared with other stigmata of recent hemorrhage (SRH).MethodsThese were post hoc multivariable analyses of a large, international, double-blind study (NCT00251979) of patients randomized to high-dose intravenous (IV) esomeprazole (PPI) or placebo for 72 h. Rebleeding rates of patients with PUB SRH treated with either PPI or placebo after successful endoscopic hemostasis were also compared.ResultsFor patients treated with placebo for 72 h after successful endoscopic hemostasis, rebleed rates by SRH were spurting arterial bleeding (FIA) 22.5%, adherent clot (FIIB) 17.6%, non-bleeding visible vessel (FIIA) 11.3%, and oozing bleeding (FIB) 4.9%. Compared with FIB patients, FIA, FIIB, and FIIA had significantly greater risks of rebleeding with odds ratios (95% CI's) from 2.61 (1.05, 6.52) for FIIA to 6.66 (2.19, 20.26) for FIA. After hemostasis, PUB rebleeding rates for FIB patients at 72 h were similar with esomeprazole (5.4%) and placebo (4.9%), whereas rebleed rates for all other major SRH (FIA, FIIA, FIIB) were lower for PPI than placebo, but the treatment by SRH interaction test was not statistically significant.ConclusionsAfter successful endoscopic hemostasis, FIB patients had very low PUB rebleeding rates irrespective of PPI or placebo treatment. This implies that after successful endoscopic hemostasis the prognostic classification of FIB ulcers as a high-risk SRH and the recommendation to treat these with high-dose IV PPI's should be re-evaluated.

Published
2017

18. Gilteritinib as Post-Transplant Maintenance for Acute Myeloid Leukemia With Internal Tandem Duplication Mutation of FLT3

Author

Levis, M, Hamadani, M, Logan, B, Jones, R, Singh, A, Litzow, M, Wingard, J, Papadopoulos, E, Perl, A, Soiffer, R, Ustun, C, Ueda Oshima, M, Uy, G, Waller, E, Vasu, S, Solh, M, Mishra, A, Muffly, L, Kim, H, Mikesch, J, Najima, Y, Onozawa, M, Thomson, K, Nagler, A, Wei, A, Marcucci, G, Geller, N, Hasabou, N, Delgado, D, Rosales, M, Hill, J, Gill, S, Nuthethi, R, King, D, Wittsack, H, Mendizabal, A, Devine, S, Horowitz, M, Chen, Y, Agura, E, Altman, J, Anagnostopoulos, A, Anand, S, Artz, A, Aulitzky, W, Balderman, S, Ballen, K, Becker, M, Beguin, Y, Berkahn, L, Berneman, Z, Bhatt, V, Bilmon, I, Bonifazi, F, Briggs, A, Bruno, B, Brunstein, C, Byrne, M, Byrne, J, Cabrero, M, Cairoli, R, Carrum, G, Cerny, J, Cheong, J, Ciceri, F, Colorado, M, Cook, R, Couriel, D, Craddock, C, Damon, L, Deol, A, Desbrosses, Y, Di Grazia, C, Di Stasi, A, Dias, A, Dorritie, K, Essell, J, Eto, T, Farag, S, Forcade, E, Frankfurt, O, Fujiwara, S, Fukuda, T, Fukushima, K, Furst, S, Goto, T, Hall, A, Hatta, S, Hicheri, Y, Horwitz, M, Hou, H, How, J, Howard, D, Hsu, W, Huynh, A, Irvine, D, Ishikawa, T, Jamieson, K, Jedrzejczak, W, Jethava, Y, Jimenez, A, Jung, C, Kanda, J, Karakasis, D, Kato, J, Kekre, N, Khera, N, Klein, A, Kobbe, G, Kornblit, B, Kota, V, Lachance, S, Leber, B, Lee, C, Lee, J, Lin, T, Liu, T, Martelli, M, Martinez, C, Matsuoka, K, Mccarty, J, Mendez, L, Michelis, F, Mineishi, S, Mohty, M, Moors, I, Motyckova, G, Mueller, L, Nakamae, H, Nakano, N, Nathan, S, Nicholson, E, Norkin, M, Ogawa, Y, Olesen, G, Oluwole, O, Pantin, J, Paulson, K, Pemberton, L, Perera, T, Piatkowska-Jakubas, B, Poire, X, Protheroe, R, Rambaldi, A, Ritchie, D, Ross, K, Rubio, M, Santarone, S, Sanz Caballer, J, Sawa, M, Schaar, D, Scheid, C, Schriber, J, Seropian, S, Shah, N, Shore, T, Gil, J, Sobecks, R, Socie, G, Sprague, K, Spyridonidis, A, Stelljes, M, Stiff, P, Stuart, R, Tanaka, M, Tandra, A, Tholouli, E, Thomas, X, Tiribelli, M, Tomlinson, B, Tsirigotis, P, Tzachanis, D, Uchida, N, Ueda, M, Valcarcel Ferreiras, D, Wagner, E, Watson, A, Weisdorf, D, Wolschke, C, Wrobel, T, Yakoub-Agha, I, Yamauchi, T, Yared, J, Yeh, S, Yoon, S, Yoshihara, S, Null, N, Levis, Mark J., Hamadani, Mehdi, Logan, Brent, Jones, Richard J., Singh, Anurag K., Litzow, Mark, Wingard, John R., Papadopoulos, Esperanza B., Perl, Alexander E., Soiffer, Robert J., Ustun, Celalettin, Ueda Oshima, Masumi, Uy, Geoffrey L., Waller, Edmund K., Vasu, Sumithra, Solh, Melhem, Mishra, Asmita, Muffly, Lori, Kim, Hee-Je, Mikesch, Jan-Henrik, Najima, Yuho, Onozawa, Masahiro, Thomson, Kirsty, Nagler, Arnon, Wei, Andrew H., Marcucci, Guido, Geller, Nancy L., Hasabou, Nahla, Delgado, David, Rosales, Matt, Hill, Jason, Gill, Stanley C., Nuthethi, Rishita, King, Denise, Wittsack, Heather, Mendizabal, Adam, Devine, Steven M., Horowitz, Mary M., Chen, Yi-Bin, Agura, Ed, Altman, Jessica, Anagnostopoulos, Achiles, Anand, Sarah, Artz, Andrew, Aulitzky, Walter, Balderman, Sophia, Ballen, Karen, Becker, Michael, Beguin, Yves, Berkahn, Leanne, Berneman, Zwi, Bhatt, Vijaya, Bilmon, Ian, Bonifazi, Francesca, Briggs, Adrienne, Bruno, Benedetto, Brunstein, Claudio, Byrne, Michael, Byrne, Jenny, Cabrero, Monica, Cairoli, Roberto, Carrum, George, Cerny, Jan, Cheong, June-Won, Ciceri, Fabio, Colorado, Mercedes, Cook, Rachel, Couriel, Daniel, Craddock, Charles, Damon, Lloyd, Deol, Abhinav, Desbrosses, Yohan, Devine, Steve, Di Grazia, Carmela, Di Stasi, Antonio, Dias, Ajoy, Dorritie, Kathy, Essell, James, Eto, Tetsuya, Farag, Sherif, Forcade, Edouard, Frankfurt, Olga, Fujiwara, Shinichiro, Fukuda, Takahiro, Fukushima, Kentaro, Furst, Sabine, Goto, Tatsunori, Hall, Aric, Hatta, Shunsuke, Hicheri, Yosr, Horwitz, Mitchell, Hou, Hsin-An, How, Jonathan, Howard, Dianna, Hsu, Wei-Hsun (Blake), Huynh, Anne, Irvine, David, Ishikawa, Takayuki, Jamieson, Katarzyna, Jedrzejczak, Wieslaw, Jethava, Yogesh, Jimenez, Antonio, Jung, Chul Won, Kanda, Junya, Karakasis, Dimitrios, Kato, Jun, Kekre, Natasha, Khera, Nandita, Klein, Andreas, Kobbe, Guido, Kornblit, Brian, Kota, Vamsi, Lachance, Silvy, Leber, Brian, Lee, Catherine, Lee, Je Hwan, Lin, Tung-Liang, Liu, Ta-Chih, Martelli, Maurizio, Martinez, Carmen, Matsuoka, Kenichi, McCarty, John, Mendez, Lourdes, Michelis, Fotios, Mineishi, Shin, Mohty, Mohamad, Moors, Ine, Motyckova, Gabriela, Mueller, Lutz, Nakamae, Hirohisa, Nakano, Nobuaki, Nathan, Sunita, Nicholson, Emma, Norkin, Maxim, Ogawa, Yoshiaki, Olesen, Gitte, Oluwole, Olalekan, Pantin, Jeremy, Paulson, Kristjan, Pemberton, Lucy, Perera, Travis, Piatkowska-Jakubas, Beata, Poire, Xavier, Protheroe, Rachel, Rambaldi, Alessandro, Ritchie, David, Ross, Kelly, Rubio, Marie-Therese, Santarone, Stella, Sanz Caballer, Jaime, Sawa, Masashi, Schaar, Dale, Scheid, Christoph, Schriber, Jeffrey, Seropian, Stuart, Shah, Nilay, Shah, Nirav, Shore, Tsiporah, Gil, Jorge Sierra, Singh, Anurag, Sobecks, Ronald, Socie, Gerard, Soiffer, Robert, Sprague, Kellie, Spyridonidis, Alexandros, Stelljes, Matthias, Stiff, Patrick, Stuart, Robert, Tanaka, Masatsugu, Tandra, Anand, Tholouli, Eleni, Thomas, Xavier, Tiribelli, Mario, Tomlinson, Benjamin, Tsirigotis, Panagiotis, Tzachanis, Dimitrios, Uchida, Naoyuki, Ueda, Masumi, Valcarcel Ferreiras, David, Wagner, Eva, Watson, Anne-Marie, Weisdorf, Daniel, Wolschke, Christine, Wrobel, Tomasz, Yakoub-Agha, Ibrahim, Yamauchi, Takuji, Yared, Jean, Yeh, Su-Peng, Yoon, Sung-Soo, Yoshihara, Satoshi, null, null, Levis, M, Hamadani, M, Logan, B, Jones, R, Singh, A, Litzow, M, Wingard, J, Papadopoulos, E, Perl, A, Soiffer, R, Ustun, C, Ueda Oshima, M, Uy, G, Waller, E, Vasu, S, Solh, M, Mishra, A, Muffly, L, Kim, H, Mikesch, J, Najima, Y, Onozawa, M, Thomson, K, Nagler, A, Wei, A, Marcucci, G, Geller, N, Hasabou, N, Delgado, D, Rosales, M, Hill, J, Gill, S, Nuthethi, R, King, D, Wittsack, H, Mendizabal, A, Devine, S, Horowitz, M, Chen, Y, Agura, E, Altman, J, Anagnostopoulos, A, Anand, S, Artz, A, Aulitzky, W, Balderman, S, Ballen, K, Becker, M, Beguin, Y, Berkahn, L, Berneman, Z, Bhatt, V, Bilmon, I, Bonifazi, F, Briggs, A, Bruno, B, Brunstein, C, Byrne, M, Byrne, J, Cabrero, M, Cairoli, R, Carrum, G, Cerny, J, Cheong, J, Ciceri, F, Colorado, M, Cook, R, Couriel, D, Craddock, C, Damon, L, Deol, A, Desbrosses, Y, Di Grazia, C, Di Stasi, A, Dias, A, Dorritie, K, Essell, J, Eto, T, Farag, S, Forcade, E, Frankfurt, O, Fujiwara, S, Fukuda, T, Fukushima, K, Furst, S, Goto, T, Hall, A, Hatta, S, Hicheri, Y, Horwitz, M, Hou, H, How, J, Howard, D, Hsu, W, Huynh, A, Irvine, D, Ishikawa, T, Jamieson, K, Jedrzejczak, W, Jethava, Y, Jimenez, A, Jung, C, Kanda, J, Karakasis, D, Kato, J, Kekre, N, Khera, N, Klein, A, Kobbe, G, Kornblit, B, Kota, V, Lachance, S, Leber, B, Lee, C, Lee, J, Lin, T, Liu, T, Martelli, M, Martinez, C, Matsuoka, K, Mccarty, J, Mendez, L, Michelis, F, Mineishi, S, Mohty, M, Moors, I, Motyckova, G, Mueller, L, Nakamae, H, Nakano, N, Nathan, S, Nicholson, E, Norkin, M, Ogawa, Y, Olesen, G, Oluwole, O, Pantin, J, Paulson, K, Pemberton, L, Perera, T, Piatkowska-Jakubas, B, Poire, X, Protheroe, R, Rambaldi, A, Ritchie, D, Ross, K, Rubio, M, Santarone, S, Sanz Caballer, J, Sawa, M, Schaar, D, Scheid, C, Schriber, J, Seropian, S, Shah, N, Shore, T, Gil, J, Sobecks, R, Socie, G, Sprague, K, Spyridonidis, A, Stelljes, M, Stiff, P, Stuart, R, Tanaka, M, Tandra, A, Tholouli, E, Thomas, X, Tiribelli, M, Tomlinson, B, Tsirigotis, P, Tzachanis, D, Uchida, N, Ueda, M, Valcarcel Ferreiras, D, Wagner, E, Watson, A, Weisdorf, D, Wolschke, C, Wrobel, T, Yakoub-Agha, I, Yamauchi, T, Yared, J, Yeh, S, Yoon, S, Yoshihara, S, Null, N, Levis, Mark J., Hamadani, Mehdi, Logan, Brent, Jones, Richard J., Singh, Anurag K., Litzow, Mark, Wingard, John R., Papadopoulos, Esperanza B., Perl, Alexander E., Soiffer, Robert J., Ustun, Celalettin, Ueda Oshima, Masumi, Uy, Geoffrey L., Waller, Edmund K., Vasu, Sumithra, Solh, Melhem, Mishra, Asmita, Muffly, Lori, Kim, Hee-Je, Mikesch, Jan-Henrik, Najima, Yuho, Onozawa, Masahiro, Thomson, Kirsty, Nagler, Arnon, Wei, Andrew H., Marcucci, Guido, Geller, Nancy L., Hasabou, Nahla, Delgado, David, Rosales, Matt, Hill, Jason, Gill, Stanley C., Nuthethi, Rishita, King, Denise, Wittsack, Heather, Mendizabal, Adam, Devine, Steven M., Horowitz, Mary M., Chen, Yi-Bin, Agura, Ed, Altman, Jessica, Anagnostopoulos, Achiles, Anand, Sarah, Artz, Andrew, Aulitzky, Walter, Balderman, Sophia, Ballen, Karen, Becker, Michael, Beguin, Yves, Berkahn, Leanne, Berneman, Zwi, Bhatt, Vijaya, Bilmon, Ian, Bonifazi, Francesca, Briggs, Adrienne, Bruno, Benedetto, Brunstein, Claudio, Byrne, Michael, Byrne, Jenny, Cabrero, Monica, Cairoli, Roberto, Carrum, George, Cerny, Jan, Cheong, June-Won, Ciceri, Fabio, Colorado, Mercedes, Cook, Rachel, Couriel, Daniel, Craddock, Charles, Damon, Lloyd, Deol, Abhinav, Desbrosses, Yohan, Devine, Steve, Di Grazia, Carmela, Di Stasi, Antonio, Dias, Ajoy, Dorritie, Kathy, Essell, James, Eto, Tetsuya, Farag, Sherif, Forcade, Edouard, Frankfurt, Olga, Fujiwara, Shinichiro, Fukuda, Takahiro, Fukushima, Kentaro, Furst, Sabine, Goto, Tatsunori, Hall, Aric, Hatta, Shunsuke, Hicheri, Yosr, Horwitz, Mitchell, Hou, Hsin-An, How, Jonathan, Howard, Dianna, Hsu, Wei-Hsun (Blake), Huynh, Anne, Irvine, David, Ishikawa, Takayuki, Jamieson, Katarzyna, Jedrzejczak, Wieslaw, Jethava, Yogesh, Jimenez, Antonio, Jung, Chul Won, Kanda, Junya, Karakasis, Dimitrios, Kato, Jun, Kekre, Natasha, Khera, Nandita, Klein, Andreas, Kobbe, Guido, Kornblit, Brian, Kota, Vamsi, Lachance, Silvy, Leber, Brian, Lee, Catherine, Lee, Je Hwan, Lin, Tung-Liang, Liu, Ta-Chih, Martelli, Maurizio, Martinez, Carmen, Matsuoka, Kenichi, McCarty, John, Mendez, Lourdes, Michelis, Fotios, Mineishi, Shin, Mohty, Mohamad, Moors, Ine, Motyckova, Gabriela, Mueller, Lutz, Nakamae, Hirohisa, Nakano, Nobuaki, Nathan, Sunita, Nicholson, Emma, Norkin, Maxim, Ogawa, Yoshiaki, Olesen, Gitte, Oluwole, Olalekan, Pantin, Jeremy, Paulson, Kristjan, Pemberton, Lucy, Perera, Travis, Piatkowska-Jakubas, Beata, Poire, Xavier, Protheroe, Rachel, Rambaldi, Alessandro, Ritchie, David, Ross, Kelly, Rubio, Marie-Therese, Santarone, Stella, Sanz Caballer, Jaime, Sawa, Masashi, Schaar, Dale, Scheid, Christoph, Schriber, Jeffrey, Seropian, Stuart, Shah, Nilay, Shah, Nirav, Shore, Tsiporah, Gil, Jorge Sierra, Singh, Anurag, Sobecks, Ronald, Socie, Gerard, Soiffer, Robert, Sprague, Kellie, Spyridonidis, Alexandros, Stelljes, Matthias, Stiff, Patrick, Stuart, Robert, Tanaka, Masatsugu, Tandra, Anand, Tholouli, Eleni, Thomas, Xavier, Tiribelli, Mario, Tomlinson, Benjamin, Tsirigotis, Panagiotis, Tzachanis, Dimitrios, Uchida, Naoyuki, Ueda, Masumi, Valcarcel Ferreiras, David, Wagner, Eva, Watson, Anne-Marie, Weisdorf, Daniel, Wolschke, Christine, Wrobel, Tomasz, Yakoub-Agha, Ibrahim, Yamauchi, Takuji, Yared, Jean, Yeh, Su-Peng, Yoon, Sung-Soo, Yoshihara, Satoshi, and null, null

Abstract

Purpose: Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with acute myeloid leukemia (AML) harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. Methods: Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. Results: Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). Conclusion: Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Published
2024

20. Orbital Support and Evolution of Flat Profiles of Bars (Shoulders)

Author

Leandro Beraldo e Silva, Victor P. Debattista, Stuart Robert Anderson, Monica Valluri, Peter Erwin, Kathryne J. Daniel, and Nathan Deg

Subjects
Galactic bar, Galaxy dynamics, Orbits, Galaxy bars, N-body simulations, Astrophysics, QB460-466
Abstract

Many barred galaxies exhibit upturns (shoulders) in their bar-major-axis density profile. Simulation studies have suggested that shoulders are supported by looped x _1 orbits, occur in growing bars, and can appear after bar buckling. We investigate the orbital support and evolution of shoulders via frequency analyses of orbits in simulations. We confirm that looped orbits are shoulder-supporting, and can remain so, to a lesser extent, after being vertically thickened. We show that looped orbits appear at the resonance ( Ω _φ − Ω _P )/Ω _R = 1/2 (analogous to the classical inner Lindblad resonance, and here called ILR) with vertical-to-radial frequency ratios 1 ≲ Ω _z /Ω _R ≲ 3/2 (vertically warm orbits). Cool orbits at the ILR (those with Ω _z /Ω _R > 3/2) are vertically thin and have no loops, contributing negligibly to shoulders. As bars slow and thicken, either secularly or by buckling, they populate warm orbits at the ILR. Further thickening carries these orbits toward crossing the vertical ILR [vILR, ( Ω _φ − Ω _P )/Ω _z = 1/2], where they convert in-plane motion to vertical motion, become chaotic, kinematically hotter, and less shoulder-supporting. Hence, persistent shoulders require bars to trap new stars, consistent with the need for a growing bar. Since buckling speeds up trapping on warm orbits at the ILR, it can be followed by shoulder formation, as seen in simulations. This sequence supports the recent observational finding that shoulders likely precede the emergence of BP-bulges. The python module for the frequency analysis, naif , is made available.

Published
2023
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21. Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study.

Author

Ravandi, Farhad, Ritchie, Ellen K, Sayar, Hamid, Lancet, Jeffrey E, Craig, Michael D, Vey, Norbert, Strickland, Stephen A, Schiller, Gary J, Jabbour, Elias, Erba, Harry P, Pigneux, Arnaud, Horst, Heinz-August, Recher, Christian, Klimek, Virginia M, Cortes, Jorge, Roboz, Gail J, Odenike, Olatoyosi, Thomas, Xavier, Havelange, Violaine, Maertens, Johan, Derigs, Hans-Günter, Heuser, Michael, Damon, Lloyd, Powell, Bayard L, Gaidano, Gianluca, Carella, Angelo-Michele, Wei, Andrew, Hogge, Donna, Craig, Adam R, Fox, Judith A, Ward, Renee, Smith, Jennifer A, Acton, Gary, Mehta, Cyrus, Stuart, Robert K, and Kantarjian, Hagop M

Subjects
Humans, Neoplasm Recurrence, Local, Thiazoles, Naphthyridines, Cytarabine, Antineoplastic Combined Chemotherapy Protocols, Disease-Free Survival, Treatment Outcome, Remission Induction, Double-Blind Method, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Leukemia, Myeloid, Acute, Kaplan-Meier Estimate, Clinical Research, Cancer, Clinical Trials and Supportive Activities, Hematology, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundSafe and effective treatments are urgently needed for patients with relapsed or refractory acute myeloid leukaemia. We investigated the efficacy and safety of vosaroxin, a first-in-class anticancer quinolone derivative, plus cytarabine in patients with relapsed or refractory acute myeloid leukaemia.MethodsThis phase 3, double-blind, placebo-controlled trial was undertaken at 101 international sites. Eligible patients with acute myeloid leukaemia were aged 18 years of age or older and had refractory disease or were in first relapse after one or two cycles of previous induction chemotherapy, including at least one cycle of anthracycline (or anthracenedione) plus cytarabine. Patients were randomly assigned 1:1 to vosaroxin (90 mg/m(2) intravenously on days 1 and 4 in a first cycle; 70 mg/m(2) in subsequent cycles) plus cytarabine (1 g/m(2) intravenously on days 1-5) or placebo plus cytarabine through a central interactive voice system with a permuted block procedure stratified by disease status, age, and geographical location. All participants were masked to treatment assignment. The primary efficacy endpoint was overall survival and the primary safety endpoint was 30-day and 60-day all-cause mortality. Efficacy analyses were done by intention to treat; safety analyses included all treated patients. This study is registered with ClinicalTrials.gov, number NCT01191801.FindingsBetween Dec 17, 2010, and Sept 25, 2013, 711 patients were randomly assigned to vosaroxin plus cytarabine (n=356) or placebo plus cytarabine (n=355). At the final analysis, median overall survival was 7·5 months (95% CI 6·4-8·5) in the vosaroxin plus cytarabine group and 6·1 months (5·2-7·1) in the placebo plus cytarabine group (hazard ratio 0·87, 95% CI 0·73-1·02; unstratified log-rank p=0·061; stratified p=0·024). A higher proportion of patients achieved complete remission in the vosaroxin plus cytarabine group than in the placebo plus cytarabine group (107 [30%] of 356 patients vs 58 [16%] of 355 patients, p

Published
2015

22. Inferior Outcomes with Cyclosporine and Mycophenolate Mofetil after Myeloablative Allogeneic Hematopoietic Cell Transplantation

Author

Hamilton, Betty K., Liu, Ying, Hemmer, Michael T., Majhail, Navneet, Ringden, Olle, Kim, Dennis, Costa, Luciano, Stuart, Robert, Alousi, Amin, Pidala, Joseph A., Couriel, Daniel R., Aljurf, Mahmoud, Antin, Joseph H., Bredeson, Christopher, Cahn, Jean-Yves, Cairo, Mitchell, Choi, Sung Won, Dandoy, Christopher, Gale, Robert Peter, Gergis, Usama, Hematti, Peiman, Inamoto, Yoshihiro, Kamble, Rammurti T., MacMillan, Margaret, Marks, David I., Nemecek, Eneida, Nishihori, Taiga, Saad, Ayman, Savani, Bipin N., Schriber, Jeff, Seo, Sachiko, Socié, Gérard, Teshima, Takanori, Verdonck, Leo F., Waller, Edmund K., Wirk, Mona, Spellman, Stephen R., Arora, Mukta, and Chhabra, Saurabh

Published
2019
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23. Ethnic differences in prevalence of actionable HbA1c levels in UK Biobank: implications for screening

Author

John G F Cleland, Naveed Sattar, Pierpaolo Pellicori, Paul Welsh, Srinivasa Vittal Katikireddi, Jill P Pell, Frederick K Ho, Stamatina Iliodromiti, Stuart Robert Gray, Carlos Celis-Morales, Jason Martin Regnald Gill, James Boyle, Lyn D Ferguson, John Forbes, Robert Lindsay, Jana J Anderson, and Claire E Welsh

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction Early detection and treatment of diabetes as well as its prevention help lessen longer-term complications. We determined the prevalence of pre-diabetes and undiagnosed diabetes in the UK Biobank and standardized the results to the UK general population.Research design and methods This cross-sectional study analyzed baseline UK Biobank data on plasma glycated hemoglobin (HbA1c) to compare the prevalence of pre-diabetes and undiagnosed diabetes mellitus in white, South Asian, black, and Chinese participants. The overall and ethnic-specific results were standardized to the UK general population aged 40–70 years of age.Results Within the UK Biobank, the overall crude prevalence was 3.6% for pre-diabetes, 0.8% for undiagnosed diabetes, and 4.4% for either. Following standardization to the UK general population, the results were similar at 3.8%, 0.8%, and 4.7%, respectively. Crude prevalence was much higher in South Asian (11.0% pre-diabetes; 3.6% undiagnosed diabetes; 14.6% either) or black (13.8% pre-diabetes; 3.0% undiagnosed diabetes; 16.8% either) participants. Only six middle-aged or old-aged South Asian individuals or seven black would need to be tested to identify an HbA1c result that merits action.Conclusions Single-stage population screening for pre-diabetes or undiagnosed diabetes in middle-old or old-aged South Asian and black individuals using HbA1c could be efficient and should be considered.

Published
2021
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24. Associations between grip strength and incident type 2 diabetes: findings from the UK Biobank prospective cohort study

Author

Naveed Sattar, Paul Welsh, Jill P Pell, Frederick K Ho, Fanny Petermann-Rocha, Stuart Robert Gray, Carlos Celis-Morales, Jason Martin Regnald Gill, Solange Parra-Soto, Gerson Ferrari, and Jirapitcha Boonpor

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction Grip strength has been associated with chronic diseases and mortality. However, current evidence of the association between grip strength and incident type 2 diabetes mellitus (T2DM) is controversial. The aim of this study was to investigate the associations of absolute and relative grip strength with incident T2DM and whether these associations differ by sociodemographic, lifestyle and adiposity-related factors.Research design and methods This was a prospective cohort study of 166 894 participants in the UK Biobank (mean age 56.5 years, 54.4% women). The outcome was T2DM incidence and the exposure was grip strength, expressed in absolute (kg) and relative (kg per kg of body weight) values. The association between grip strength and T2DM incidence was investigated using Cox-proportional regression.Results The median follow-up was 5.3 years (IQR: 4.7–6.1). During this time, 3713 participants developed T2DM. Lower grip strength was associated with a higher risk of T2DM in both sexes. Those in the lowest quintile of absolute grip strength had a 50% higher risk in men (HR: 1.50 (95% CI: 1.30 to 1.73)) and 25% higher risk in women (HR: 1.25 (95% CI: 1.06 to 1.47)) compared with those in the highest quintile. For relative grip strength, risk of diabetes was more than double for men (HR: 2.22 (95% CI: 1.84 to 2.67)) and 96% higher for women (HR: 1.96 (95% CI: 1.52 to 2.53)) in the lowest compared with highest quintiles.Conclusions Grip strength is associated with a higher risk of T2DM incidence in both men and women independent of important confounding factors including age, deprivation, adiposity and lifestyle. However, the associations were stronger when grip strength is expressed relative to body weight, which could reflect the importance of muscle quality.

Published
2021
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27. Cancelled operations: a 7-day cohort study of planned adult inpatient surgery in 245 UK National Health Service hospitals

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Moonesinghe, S. Ramani, Wong, Danny J.N., Harris, Steve K., Bedford, James, Boney, Oliver, Chazapis, Maria, Drake, Sharon, Farmer, Laura, Gilhooly, David, Goodwin, James, Lourtie, Jose, Wagstaff, Duncan, Grocott, Mike, Sneyd, Robert, Batchelor, Anna, Brett, Stephen, Plowright, Catherine, Shrestha, Suman, Shawyer, Richard, Ahmed, Shafi, Khondoker, Mizan, Nathanson, Mike, Cripps, Paul, Research & Audit Federation of Trainees (RAFT), Anaesthetic Audit and Research Matrix of Yorkshire (AARMY), Intensive Care & Anaesthesia Research Network of North East Trainees (INCARNNET), Merseyside Anaesthetic Group for Improving Quality (MAGIQ), Midlands East Research by Critical Care and Anaesthetic Trainees (MERCAT), North West Research and Audit Group (NWRAG), Oxford Critical Care Anaesthetic Research Enterprise (OxCCARE), Pan-London Peri-operative Audit & Research Network (PLAN), Scottish East Quality Improvement & Research Academy (SEQuoIA), SESSA Quality Improvement and Research Network (SQUARES), Severn Trainees Anaesthetic Research (STAR), South West Anaesthetic Research Matrix (SWARM), South Yorkshire Hospitals Audit and Research Collaboration (SHARC), Southcoast Peri-operative Audit and Research Collaboration (SPARC), Welsh Anaesthetic Audit Research & Engagement Network (WAAREN), West Midlands Trainee Research Anaesthesia & Intensive Care Network (WMTRAIN), Rawat, Shilpa, Sathe, Sonia, Campbell, Alison, Anandarajah, Janakan, Ball, Nicola, Bandara, Lalindra, Barnes, Dennis, Chapman, Catherine, Connor, Lynda, Cook, Amanda, Ebejer, Amanda, Evans, Samantha, Gallagher, Maire, Goff, Sarah, Halfacree, Irina, Harford, Rachel, Harris, Catherine, Jackson, Rebecca, James, Kathryn, Jones, Claire, Jones, Sharon, Malinovszky, Kathy, Mungai, Serah, Nageswaran, Hari, Perumal, Anand, Pudge, Harriet, Quinn, Leanne, Sheppard, Thomas, Smith, Trudy, Spargo, James, Storton, Sharon, Thomas, Caradog, Thomas, Charlotte, Tyrrell, Samuel, Vale, Owen, Williams, Catrin, Williams, Marie, Williams, Tom, Winfield-Young, Lewys, Worrell, Helen, Moloney, Dermot, Chuni, Chandini, Comara, Jasna, Conway, Brian, Eagle, Zara, Foster, Greg, Platt, Chris, Thorne, Alison, Hee, Wendy Lum, Armstrong, Lisa, Brennan, Albert, Burns, Justine, Busby, Chantal, Couch-Upite, Mechele, Dooks, Emma, Dunlop, Sally, Eijk, Anya, Govindaraju, Ramana, Gregory, Tamsin, Grover, Alka, Hairsine, Brigid, Hennell, Sarah, Hill, Philippa, Hollins, Thomas, Hood, Julian, Horner, Lisa, Hothersall, Helen, Ingham, Rachel, Jackson, Richard, Kitching, Amy, Kurasz, Claire, Munsie, Sarah, Nemeth, Ildiko, Paley, Carole, Premraj, Prabhakaran, Redhead, Sue, Scriven, John, Shaw, Alison, Shenton, Liz, Shiva, Hemantha, Snell, Josie, Sootheran, Lucy, Stewart, Josephine, Swinton, Frank, Totten, Claire, Varghese, Liz, Vest, Sarah, Wetherell, Ben, Hamlyn, Vincent, Tozer, James, Alce, Timothy, Bopanna, Poonam, Draper, Kevin, Emmett, Lucy, Falkner, Phillippa, Fisher, Ellie, Griffiths, Cat, Gunter, Una, Harris, Rebecca, Hashmi, Saima, Jewitt, Helen, Lodhi, Sonal, Organ, Angie, Owen, Elana, Taylor, Frances, Tritean, Maria, Wassall, Richard, Woolley, Jade, MacGregor, Mark, Atkinson, Claire, Croft, Maria, Frost, Victoria, George, Richard, Gray, Catherine, Kuttler, Anja, Lalani, Christina, Peers, Beth, Sharpe, Lisa, Skeoch, Christopher, Tarft, Hayley, Tyson, Emma, Wrigley, Martha, Qadri, Shabir, Abbas, Tahir, Barot, Niraj, Cole, Steve, Ganesh, Ritesh, Groves, Christopher, Iles, Lindsey, Petkova, Hristina, Rau, Clovis, Roberts, Jack, Shakir, Nadeem, Chaurasia, Sunil Kumar, Brown, Julia, Cunningham, Mishell, Daniels, Allison, Gannon, Emily, Haines, Annette, Johnson, Nicola, Ogle, Paul, Perumal, Srinivasan, Zeidan, Lisa, Torrance, Hew, Anwar, Sibtain, Gooneratne, Mevan, Raj, Ashok, Abbott, Tom, Ashton, Laura, Brown, Katherine, Butterfield, Emma, Fenn, Jon, Forsyth-Jones, Tim, Garth, Thomas, Gleeson, Liam, Haines, Ryan, Jacobs, Benjamin, Jyothiraj, Haren, Madhi, Shareef, Marriot, Charlotte, Martin, Rebecca, McMillan, Timothy, Menon, Arun, Mohr, Otto Ernst, Muelmenstaedt, Maria, Naeem, Hanzla, Nagendram, Myura, O'Connor, Cormac, Pang, Ching, Plummer, Kimberley, Rob, Zak, Sellers, Dan, Shaw, Michael, Smith, Christopher, Taylor, Tom, Thorat, Priya, Van Rensberg, Gerhardus, Walker, Sophie, Waqas, Farkhunda, Wicks, Peter, Wirth, Daniel, Armanious, Samuel, Allen, Kellie, Bruni, Salvatore, Burijinti Chenna, Keshava Reddy, Kaliappan, Agilan, Ocampo, Madelaine, Percuin, Adrian, Riches, Joanne, Saclot, Louie, Sevillano, Annaliza, Vertue, Mark, Knowlden, Peter, David, Beena, Gajendragadkar, Pushpaj, Gladstone, George, Hammerbeck, Henry, Iaverdino, Marina, Lilley, Carina, Linton-Willoughby, Ben, Murrell, Daniel, Patro, Shweta, Richie-Mclean, Susanna, Turnbull, Marc, Vatsala, Padmanabhan, McCourt, Killian, Black, Nick, Coary, Ciara, McCarter, Jonathan, Murphy, Alexandra, Pugh, Richard, Littler, Chris, Clements, Stephan, Bairkdar, Linda, Bennett, Gillian, Bird, Tom, Bolger, Annette, Dhar, King, Ene, Raluca, George, David, Haron, Dhania, Hobson, Lucie, Iqbal, Saba, Irvine, Lizzie, Lewis, Sion, McCallum, Roisin, O'Donovan, Benjamin, Patrick, Christopher, Perman, Christopher, Rahman, Nowfal, Roberts, Iolo, Sutcliffe, William, Towers, Tammy, Waite, Alicia, Wright, Stella, Pilsbury, Jane, Allan, Michael, Allen, Cody, Carden, Nikkita, Cotterill, Amanda, Cullis, Kerry, Eden, Daniel, Farmer, Nicola, Galloway, Andrea, Geoghegan, James, Gilani, Ahmed, Hard, Kelly, Hasan, Khalid, Horner, Christopher, Iqbal, Virginia, Lowe, Julie, Mallavalli, Ravindra, McCooty, Shanteela, McKillop, Sian, Mellers, Diane, Mukherjee, Ronan, Nicholas, Michelle, O'Hara, Chloe, Osborne, Fiona, Plunkett, Emma, Sharih, Gauhar, Westwood, John, Whapples, Annabelle, Whitehouse, Diane, Williams, Lucinda, Yasin, Bilal, Cupitt, Jason, Brown, Janette, Stoddard, Emma, Balasubramaniam, Madhu, Athanasopoulos, Paul, Bhatti, Mohammad, Blood, Laura, Buckley, Hugo, Chadwick, Julie, Cocks, Shirley, Fradkin, Deborah, Hetherington, Emily, Hill, Rebecca, Hull, Rob, Loftus, Alison, McKenna, Emma, Mcmanoman, Lucy, Milian, Lauren, Mistry, Raksha, Murthen, Lisa, Parkinson, Dave, Rhead, Kat, Sandbach, Peter, Walker, Ciara, Wheatley, Emma, Spencer, Robert, Alderson, Stephen, Bull, Christopher, Butterworth, Rachel, Cousins, Simon, Goellner, Sarah, Greasley, Mark, Lyle, Fiona, Munro, Michael, Northey, Martin, White, Stuart, Harrison, Alex, Whitney, Paul-Simon, Drake, Jeremy, Babla, Rohan, Bharti, Ash, Cole, Stephen, Crotty, Stephen, Farrow, Amy, Golhar, Anil, Indoe, Peter, Jackson, Rosada, Latif, Mariam, Leong, Melvin, Lewith, Henry, Maton-Howarth, Matthew, Millar, Victoria, Millette, Ben, Oliver, Hannah, Ralhan, Vandita, Rashid, Yasir, Rivero-Bosch, Maria, Rizvi, Sana, Saleh, Rosahn, Venkatesh, Harisg, Wilson, Kate, Nair, Ashok, Basvi, Precious, Bell, Gillian, Edwards, James, Lee, David, Luo, Guanmei, Mewies, Clare, Qureshi, Arif, Sohail, Behzad, Valap, Sachin, Hill, Stephen, Bhuwanee, Deepti, Chan, James, Dereix, John, George, Allen, Ghafoor, Tasmeen, Gold, Emma, Haigh, Daniel, Harding, David, Janardhana, Bhavia, Jayan, Jithu, King, James, Laloë, Pnt, Pearce, Lauren, Pruthi, Amit, Roscoe, Eleanor, Seharawat, Deepak, Stubbington, Mark, Vanjari, Vinayak, Venkataraman, Anantharaman, Yen, Serena, Patil, Vishal, Chan, Charles, Davenport, Garry, Featherstone, Peter, Fourie, Petrus, Hall, Christopher, Mahidik, Preeti, Masoni, Elisa, Ortu, Andrea, Patil, Anita, Pickett, Janet, Sharma, Sandeep, Goodwin, Naomi, Allen, Lucy, Anderson, Nathan, Bateson, Ethan, Bhatia, Sanchita, Churchill, Sara, Cohen, Leon, Colhoun, Patrick, Dunn, Charlotte, Durie, Carys, Elgarf, Sarah, Ferry, Jenny, Guilford, Jeremy, Halligan, Claire, Harrison, Jade, Hayes, Dominic, Holst, Ben, Hughes, Rhys, Hunt, Thomas, Jackson, John, Kohler, George, Kriger, Michael, Kulikouskaya, Svetlana, Kurani, Amit, Maden, Charlotte, Moore, Alex, Mounce, Adam, O'Donnell, Alice, Sparrow, Robert, Sutherland, Jayne, Hanison, James, Bansal, Sujesh, Greenwood, Nick, Alkholany, Mahmoud, Apple, Zoe, Asif, Anam, Bhardwaj, Neeraj, Braid, Karl, Coates, Rebecca, Czukowska, Liliana, Elliott, Lauren, Fang, Li, Greenlee, Hannah, Maria, Jashmin, Mostafa, Tarek, Patil, Amarjeet, Weigert, Andrea, Matson, Alexandra, Adamson, Christine, Barclay, Philip, Barker, Amy, Bautista, Carina, Biswas, Suman, Bull, Rhian, Carungcong, Jaime, Christoper, Fenner, Cifre, Elna, Clancy, Olivia, Friedman, Lauren, Frunza, Gabriella, Habib, Sadia, Keerthikumar, Hindusha, Kirwan, Ursula, Laycock, Helen, Leir, Sarah, Maduekwe, Victor, Martella, Carmela, Meritahti, Minna, Nundlall, Kribashnie, Oblak, Metod, Panesar, Kirat, Peters, Timothy, Pett, Eleanor, Routley, Catriona, Samani, Amee, Santhirapala, Vatsharlan, Sayan, Amrinda, Sisson, Alice, Svensson, Marie-Louise, Thankachen, Mini, Tilley, Bernadette, Topham, Charlotte, Visvendra, Sathya, Warrington, Anna, Wibberley, Helen, Spittle, Nick, Andrews, Mia, Beavis, Sarah, Bernotaitis, Daiva, Chinna, Shalini, Church, Helen, Edwards, Sian, Ford, Nicky, Hazeldine, Sarah, Hudson, James, Macey, Claire, Morgans, Matthew, Toms, Julie, Whileman, Amanda, Woodward, Jan, Wright, Stephanie, Nariani, Jaya, Clark, Sam, Duniec, Larysa, Slorach, Marc, Allan, Ashley, Burrill, Bryony, Fairless, Lynn, Francis, Nicholas, McAdam, Colin, Sheriff, Julie, McLoughlin, Thomas, Arshed, Shayan, Bird, Clare, Campbell, Debbie, Chinery, Elaine, Onya, Enoch, Perry, Ryan, Sabugueiro, Jose Miguel, Shatanda, Lydia, Sheik, Muzaffar, Jo simpson, Wong, Gabriela, Yun-Han, Chen, Wilson, Lawrence, Adshead, Duncan, Castillo, David, Faulkner, Maria, Gibson, Kim, Keogh, Tara, Michlig, Sam, Perritt, Elizabeth, Ridler, Simon, Tizzard, Kate, Troy, Anne, Rafi, Amir, Melsom, Helen, Atkinson, Vikki, Azad, Tariq, Bashliyski, Vladimir, Brown, Ellen, Clark, Sarah, Cowton, Sister Amanda, Deane, Jill, Dent, Jean, Duckett, Karin, Duncan, Louise, Hooper, Nicholas, Johnson, Tom, Kay, Andrea, Kelly, Donna, Kent, Melanie, Knight, Jo, McCarroll, Christina, Newby, Annie, Potts, Kathryn, Roe, James, Rollins, David, Sarwar, Asia, Schofield, Lewis, Skelton, Deborah, Somanath, Sameer, Taysum, Peter, Temple, Julie, Udall, William, Varin, Jane, Venyo, Lucy, Warin, Martin, Wood, Shelly, Dhileepan, Srinivasan, Saibaba, Ravishankar Jakkala, Stewart, Emma, Warwick, Eleanor, Pemberton, Omar Alex, Garmash, Maryna, Griffiths, Rhys, Hale, Suzi, Lahloub, Fatma, Lynch, Ceri, Majeed, Abbas, Patchell, Ifan, Quinton, Jennifer, Sedghi, Babak, Wallis, Stephanie, Mansoor, Sange, Belagodu, Zakaulla, Dastur, Shirin, Fuller, Bridget, Hayes, Imogen, Keshkamat, Ashwini, Monantera, Georgia, Sandhar, Roxana, Sivakumaran, Shamini, Thomas, Megan, Torne, Manish, Turner, Sherma, Wakefield, Phillipa, Rogerson, David, Addleton, Catherine, Aju, Lisha, Appleby, Marie, Barnes, Elizabeth, Boateng, Trish, Carrick, Laura, Coulborn, Elaine, Darbyshire, Rebecca, Downes, Charlotte, Fitzgerald, Jodie, Hall, Linda, Harvey, Laura, Hassan, Amr, Holding, Kathleen, Hufton, Lianne, Humphries, Louise, Humphries, Ryan, Inman, Laurence, Issit, Nicole, Longhurst, Sarah, MacGregor, Melody, Mistry, Trusha, Mohamed, Mona, Otieno, Charlene, Read, David, Scott, Michelle, Singleton, Abbie, Smith, Jill, Sohal, Aariana, Tou, Samson, Unsworth, Vanessa, Wan, Richard, Worth, Christopher, Dobson, Richard, Buckley, Rose, Codling, Rachel, Hunter, Cain, Jackson, Jenny, Lowrie, Caroline, McMillan, Catherine, McNab, Raj, Richardson, Max, Sylvester, James, Watkin, Anna, Chambers, Jonathan, Bown, Rachel, Christie, Colin, Dukes, Stephanie, Horton, Sarah, Rees, Andrew, Williams, Patricia, Williams, Sarah, Pierson, Richard, Agarwal, Nipun, Allcock, Clare, Banga, Irmeet, Baron, Kirsty, Cole, Andrea, Dalay, Santinder, Gidda, Ranjit, Lo, Phillip, Merotra, Susan, Newton, Kathryn, Riddell, Zoe, Sonksen, Julian, Jamadarkhana, Sunil, Alcock, Chanice, Allen, Wei Lin, Baker, Pearl, Beadle, Hannah, Bramall, Jon, Chiravasuta, Radu, Chohan, Amina, Christofides, Angela, Cook, Angela, Cotta, Janet, Cruz, Carina, Gilmore, Jemma, Hills, Vicky, King, Kathryn, McClelland, Lucy, Nishimura, Sei, Nyathi, Rumyana, Panagoda, Prasan, Peacock, Louise, Shinn, Emma, Spencer, Sophie, Vianzon, Mayumi, Kapoor, Ritoo, Natarajan, Nagendra, Moore, Joanna, Amoakwa-Adu, Freda, Bahlool, Sinan, Cosier, Tracey, Driscoll, Sarah, Dulea, Claudia, Feneley, Andrew, Fletcher, Marcus, Hammad, Walid, Hazelton, Tracy, Hoyland, Kim, Katyayani, Bennur, Lloyd, Catherine, Moon, Angela, Musselwhite, Janine, Nair, Ganesh, O'Donnell, Joshua, Patankar, Pushkar, Redington, Katy, Sange, Aalia, Snazelle, Mark, Srbljak, Vanja, Stead, Richard, Tariq, Ismail, Thomas, Janine, Turney, Sharon, Chukkambotla, Srikanth, Mathew, Aji, Lie, Jason, Badsha, Zackriah, Bews, Sam, Bhandari, Kumud, Cartmell, Catherine, Cox, Greg, Desai, Hawa, Doran, Mark, Duberley, Stephen, Fitchett, Jill, Forrest, Diane, Freeman, David, Gani, Asif, Gedling, Catherine, Giles, Jessica, Goddard, Wendy, Gregson, Linda, Grimes, Yvonne, Hammond, Bev, Hartley, Janice, Hudson, Gemma, Ibrahim, Ramez, Iqbal, Nasreen, Jewers, Karen, Johnston, Brian, Kakkar, Abhishek, Koczka, Istvan, Lovell, Matt, Mahmoud, Mohamad, Melvin, Cathie, Milner, Matt, Moss, Nicky, Patel, Jeet, Perry, David, Pollard, Mike, Reed, Stephanie, Rennie, Gillian, Riley, Karen, Samuels, Sherrie, Simionescu, Ioana, Sissons, Lorna, Traynor, Stephen, Tucker, Daniel, Vetuz, Glenn, Whalley, Gillian, Marshall, Philippa, Arnold, Tim, Brookes, Jamie, Cowley, Anne, Delascasas, Ruth, Edmunds, Emma, Espitalier-Noel, Dominic, Jeevananthan, Rajeev, Law, Jenni, Mintrim, Kelly, Reid, Jack, Terry, Jackie, Verma, Manish, Zahra, Jean-Paul, Thorning, Geoff, Bailes, John, Dawson, Lindsay, Donovan, Clare, Gan, Jo Han, Jeyarajah, Kaya, Selman, Andrew, Woods, Justin, Csabi, Peter, Choo, Yin Yong, Das, Saheli, Denford, Clare, Desai, Mihir, Dimber, Rahul, Ellisy, Khaled, Griffiths, Ben, Lee, Sindy, Linnett, Vanessa, Daniels, Alex, Perkin, Sadie, Ritzema, Sister Jenny, Storey, Sister Bryony, Wood, Christine, Orme, Robert, Koh, Sock, Banks, Charis, Barker, Oliver, Beames, Susan, Brown, Aislinn, Corbett, Lucy, Dalton, James, Davis, Fiona, Edmunds, Matthew, Gatfield, Will, Gerrans, Edmund, Hickish, Tom, Hignell, Emily, Hiltout, Paula, Johnston, Helen, Miller, Sam, Mullender, Jo, O'Connell, Susan, Rosedale, Kath, Samuel, Katie, Vannahme, Milena, Baigel, Gary, Grayland, Sarah, Hawley, Victoria, McAffrey, Laura, Peggler, Suzannah, Stevens, Joe, Bidd, Heena, El-Boghdadly, Kariem, Zucco, Liana, Adelaja, Yemi, Bhattacharyya, Sanjoy, Bickmore, Elsie, Body, Suzanne, May-Ling Cheung, Jenny, Chowdhury, Priaykam, Cuddihy, Joshua, Ekwere, Ndi, John-Baptiste, Ange Lise, Kelly, Paul, Leslie, Daniel, Mon, Wint, Muzengi, Natasha, Ong, Cheng, Pattni, Nisha, Potter, Thomas, Stanton, Elena, Zaky, Maryam, Partridge, Richard, Bromhead, Helen, Evans, Peter, Griffin, Denise, Kinsella, J. Joseph, Knight, Alexander, Lewis, Rosemary Anna, Lightfoot, Heidi, Martin, Jane, Mupudzi, McDonald, Nahajski, Katherine, Oladele, Segun, Ottaway, Julia, Petley, Stephen, Sheldrake, Ian, Stewart, Alexander Michael, Stokes, Aaron, Trodd, Dawn, Varsani, Nimu, Walshe, Eleanor, Brown, Caroline Wrey, Huntley, Martin, Baldry, Natalie, Bennett, Caroline, Earl, Sophie, Guy, Joyce, Peat, Maggie, Stephenson, Lorraine, Tan, Hao Ern, Wills, Louise, Yare, Michelle, Yeung, Joyce, Antrolikar, Supriya, Atterbury, Katie, Baba, Fayaz, Bancroft, Hollie, Begum, Safia, Bellamy, Mary, Couper, Keith, Evans, Lucy, Flight, Rachel, Frankling, Catriona, Ganesh, Srikant, Gresty, Joanne, Joslyn, Ruth, Kadiri, Salma, Karimi, Aalisha Mariam, Kerr, Amy, Melody, Teresa, Moore, Faye, Morrish, Jennifer, O'Sullivan, Mary, Patel, Vanisha, Reeves, Eleanor, Robley, Richard, Sampson, Julia, Sangombe, Mirriam, Shabangu, Vusumuzi, Sheppard, Lucy, Stafford, Sam, Sutton, Peter, Taylor, Joanne, Turner, James, Velho, Rochelle, Webb, Joanne, Webber, Linda, Werpachowska, Ewa, Wilkinson-Guy, Lisa, Papageorgiou, Constandinos, Bisonoothan, Sohan, Casely, Emma, Casey, Carina, Kam, Elisa, Landers, Geraldine, Pearse, Laura, Raja, Meera, Solomon, Daniel, Stoyanov, Plamen, Talati, Chiraag, Arunachalam, Hari, Ashton, Victoria, Full, Jens, Green, Samira, Gratrix, Andrew, Abernethy, Caroline, Clarke, Abigail, Desai, Pallavbhai, Martinson, Victoria, Parekh, Ravi, Phillips, Mirain, Raina, Anju, Raut, Sarah, Smales, Chris, Smith, Neil, Ugochukwu, Ruth, Willis, Matt, Ignatova, Zhana, Gill, Stuart, Agarwal, Sunita, Barclay, Harry, Campbell, Brian, Collingborn, Maggie, Dagnan, Richard, Davies, David Steven, Dhaliwal, Randeep, Dharmarathna, Ishan, Doriaswami, Yuvraj, Evans, Hywel, Foly, Ahmed, Francis, John, Green, Tim, Hassanin, Ahmed, Havalda, Peter, Huda, Ahmad, Jones, Beryl, Khoju, Ramesh, Lackmann, Maria, Mensah, Kofi, Nwaefulu, Christopher, Schmidt, Ilona, Selvraj, Gopinath, Skarbit, Norbert, Suganthi, Obla, Zeber, Jacek, Nagaratnam, Vidhya, Mukherjee, Smitangshu, Kirby, Sue, Arnold, Glenn, Bendel, Daniel, Boynton, Claire, Carvell, James, Carver, Anthony, Clayton, Matt, Desai, Keyury, Fadhlillah, Fiqry, Georgiou, Christiana, Jayakumar, Vineetha, Jeanes, Lara, Jhugursing, Mhairi, Jose, Jasmine, Karsten, Emma, Kormendy, Flora, Lewis, Stephanie, Lloyd, Dafydd, Mautadin, Francisca, McCahill, Claire, McInerney, Susan, Morland, Laura, Morsman, Elaine, Nayee, Sunny, O'Callaghan, David, Pickford, Emily, Pratap, Bhavesh, Rao, Chandana, Shah, Alka, Smith, Stephen, Smyth, Claire, Souleimanova, Icel, Templeton, Maie, Upadhyaya, Kavita, Uren, Sophie, Voralia, Shree, Wilson, Rebecca, Kushakavsky, Vlad, Ang, Justin, Beeby, Debroah, Bell, Stephanie, Boys, Helen, Brixey, Sue, Chabo, Cathleen, Cubitt, Lynsey, Dawson, Maggie, Finch, Jenny, Lewis, Robert, Purewal, Bally, Pyae, Kaung, Ramsey, Judi, Scoones, Ben, Debreceni, Gabor, Tarin, Obaid, Zondo, Nicola, Bothma, Pieter, Carmichael, Jack, Ferreira, Teresa, Goffin, Kelly, Gurung, Sarada, Kundu, Ashish, MacLennan, Sarah, Murray, Theresa, Verma, Karan, Wilson, Graeme, Winthein, Aleinmar, Jakkampudi, Satyanarayan, Ahmed, Muneeba, Baines, Duncan, Beirnes, Charmaine, Braybrook, Chrissy, Fernandez, Olga, Gracey, Jayshree, Guha, Snehasish, Jain, Arihant, Krishnaiyan, Raghavendran, Moody, Thomas, Novaga, Jo, Tait, Frances, Tate, Jemma, Taylor, Jennifer Claire, Waldron, Molly, White, Sonia, Gupta, Anish, Botfield, Claire, Ahmed, Mohamed, Ashton, Lizzie, Bailey, Andrew Robert, Banugo, Pele, Birch, Sian, Boyle, Henry, Brown, Alice, Chen, Mark, Connolly, Lucy, Dalal, Viral, Edwards, Alexandra, Elnour, Shaima, Faccini, Timothy, Floyd, Theodore, Georgiou, Thomas, Gill, James, Hedley, Russell, Hopkins, Philip, Kumar, Roshmi, Michell, Alice, O'Shaughnessy, Rhiann Marie, O'Sullivan, Laura, Pai, Seema, Parsons, Benjamin, Peltola, Laura, Penhaligan, Beth, Place, Merate, Ramsden, Jonathan, Ratnayake, Gamunu, Shammas, Kathy, Watts, Ali, Williams, Thomas, Woodham, Valantine, Puranik, Sarang, Crooks, Jennifer, Dean, Ania, Honstvet, Chris, Hunter, Katherine, Steynberg, Sarah, Swain, Andrew, Laha, Shondipon, Bonner, Alex, Doyle, Donna, Fallon, Robert, Verlander, Mark, Williams, Alexandra, Yardley, Richard, Whiteley, Simon, Ahmed, Zaid, Child, Ossian Aukland, Black, Sheila, Calderwood, Jamie, Chapman, Andy, Collin, Robert, Dwornik, Kinga, Gallagher, Kate, Gardener, Michelle, Harrop, Gareth, Hart, Peter, Howcroft, Clare, Ilyas, Carl, Kempanna, Umakanth, Krishnamurthy, Gnanshree, Kumara, Paramesh, Loh, LI Lian, Morgan, James, Pipe, Jonathan, Sathiapillai, Anand, Stones, John, Wilby, Elizabeth, Shephard, Buzz, Agarwal, Manju, Bolonenkova, Tatyana, Dunlop, Lisa, Duraisamy, Karthick, Kelly, Jenna, Nurmi, Eveliina, Patel, Mitul, Perry, Jonathan, Prior, Charles, Reece-Anthony, Rosie, Rose, Bernd Oliver, Rowland, Katie, Van Ross, Jennifer, McNamara, Helen, Permall, Natasha, Robertson, Gillian, Siew, Sarah, Smith, Amy, Spearritt, Sue, Verma, Dipali, Williams, Rhys, Zaidi, Suhail, Clayton, Samantha, Goddin, James, Joy, Stuart, Malhotra, Vikram, Mindel, Samuel, Neilson, Zoe, Wijesuria, Shanelle Tharuka, Wilkins, Ryan, Mukherjee, Kirtida, Bradley, Andrew, Coetzee, Samantha, Crook, Alexandra, Emeakaroha, Eunice, Frenkiel, Marek, Hatton, Tom, Kamraj, Kootharajan, Long, Natalie, Manikundalam, Badrinath, Peiris, Muditha, Roche, Matthew, Sandhu, Banher, White, Nichola, Woods, Annette, Yarnold, Adam, Price, Nicolas, Ashe, Marion, Disney, Tom, Dixon, Caroline, Dodds, Emily, El-Sheika, Sarah, Hameed, Yasir, Jones, Rob, Kanal, Karan, Ranaweera, Sanjeewa, Ripoll, Simon, Russell, Nicki, Smith, Sally Anne, Tung, Swee Ang, Emerson, Bruce, Apps, Victoria, Austin, Mandy, Catchpole, Laura, Catley, Christine, Child, Jenny, Cranmer, Karen, Dawson, Lizzie, Farr, Beth, Gerrish, Helen, Gibson, Sian, Gunn, Jacqueline, Holland, Kim, James, Lorri, Jayasekera, Dushyanthi, Lester, Yvonne, Lyle, Amanda, McNeela, Fiona, Oborska, Aneta, Pennington, James, Perkins, Lauren, Robinson-Perrie, Hollie, Shillito, Lauren, Singizi, Bryan, Smolen, Susan, Topliffe, Joanne, Vowles, Ben, Whybro, Natalie, Wijunamai, Amon, Willsher, Lucy, Wootton, Joanne, Varma, Sandeep, Atkinson, Philip, Buckley, Sarah, Darian, Thelma, Dhamaratne, Sachini, Gould, Richard, Graham, Laura, Hirst, Charlotte, Peeling, Andrew, Prentice, Saxon, Rajasekar, Naresh, Rose, Alastair, Smith, Craig, Wilkinson, Kate, Stewart, Richard, Chevis, Chrissie, Ekpa, John, Greig, Nurse Sara, Hinch, Nurse Rebecca, Holder, Carole, Makris, Nikolaos, Moran, Nurse Louise, Padilla Harris, Nurse Cheryl, Scarletta, Nurse Diane, Smith, Jeanette, Sara-Beth Sutherland, Nurse, Turner, Joanne, Valentine, Peter, van Manen, Amelia, Walia, Nurse Sonia, White, Nurse Charlotte, Wilson, Georgina, Wren, Nurse Lynn, Wright, Nurse Francesca, Faulds, Matthew, Agius, Claire-Marie, Ahmed, Raheel, Ahmed, Sameer, Alva, Arjun, Bird, Rachael, Buckley, David, Calder, Verity, Clark, Caroline, Craven, Emily, Cullen, Katherine, Davis, John, Diamond-Fox, Sadie, Doherty, Helen, Dutta, Bhaskar, Fortune, Jonathan, Gatehouse, Alexandra, Gibson, Jane, Hay, David, Hillier, Steve, Hindmarch, Paul, James, Michael, Keshvara, Kiran, Kotur, Karuna, Lawley, Peter, Lochanie, Nimali, Macbeth, Lisa, Madhu, Yamuna, Marcangelo, Sam, McShane, Lesley, Morgan, Amy, Mowat, Stephen, Nelson, Joshua, O'Leary, Denis, Partridge, Jennifer, Pearson, Janaki, Poulton, Tom, Prasad, Sneha, Protheroe, Kay, Qureshi, Adnaan, Rangaswamy, Girish, Richardson, Victoria, Scott, Carmen, Smallshaw, Karen, Soliman, Abdelrahman, Soulsby, Graham, Wahed, Anna, Walker, Iain, Welch, Sarah, Wilson, Jessica, Winkley, Elaine, Womack, Jonathan, Mitchell, Joellene, O'Brien, Peter, Callaghan, Debbie, Clarke, Ruth, Foggo, Graeme, Gilmour, Danielle, Hickey, Stephen, Hii, Stephanie, Livingstone, Susan, McAtear, Megan, Meehan, Sharon, Milne, Gemma, Small, James, Williams, Dewi, Jardine, Catherine, White, Graham, Wright, David, Hunter, Katie, Fleming, Gillian, Marc Hastie, P.A.-A., Hunter, Catherine, Lockhart, Jennifer, Reid, Kirsten, Robb, Hilary, Harten, Johann, Crooks, Barbara A., Ratnasabapathy, Urmila, Staber, Manfred, Pettigrew, Tom, Varveris, Daphne, Brett, Michael, Appleton, Richard, Briskoe, Michael, Brown, Graeme, Brown, Stewart, Christie, Fiona, Coady, Guy, Cowan, Richard, Drysdale, Alice, D'Sylva, Stewart, Edgar, Paul, Finnie, Graeme, Gardner, John, Gupta, Shub, Hall, Colin, Hamilton, Jane, Hunter, Laura, Ikram, Umairali, Imrie, Gregor, Kerr, Euan, Kinsella, Michael, Kommer, Maya, Lafferty, Brian, Lochrin, Christopher, Lovejoy, Tom, Loy, Maria, MacLean, Aillison, MacPherson, David, Marshall, Cara, Mawhinney, Ruth, McAteer, Claire, McCaul, Prof James, McCusker, Michael, McDowall, Katherine, McGovern, Christopher, Mckie, Stewart, Morrison, Melanie, Mulla, Suleman, Neale, Elizabeth, Niciu, Cristina, Ong, Su Ying, O'Sullivan, Finbar, Parcell, Sophie, Ramsay, Sarah, Robson, Rebecca, Roy, Nithin, Samuel, Jasmine, Scotland, Gemma, Sharma, Natasha, Slade, Kate, Soosay, Alvin, Soulsby, Charlotte, Steuart, Lois, Stevenson, Sara, Sweeney, Laura, Tan, Kerwei, Taylor, Calum, Th'ng, Francesca, Thompson, Caroline, Wardlow, James, Watson, Martin, Williams, Robin, Woodier, James, Young, Simon, Robinson, David, Howes, Jacqueline, Berwick, Scott, Boyle, Andrew, Brown, Neil, Celnik, Anna, Coleman, Alistair, Elwkhiee, Mohamed, Fernandes, Mario, Hanlon, Katie, MacLean, Sarah, Morgan, Rhian, Edgar, Jonathan, Chapman, Roddy, Razouk, Khaled, Atrah, Ali, Bhat, Sunny, Bramma, Yvonne, Campbell, Euan, Campbell, Rachel, Cormack, Anna, Dalchow, Stephan, Dodd, Ammy, Ferguson, Laura, Ferraioli, Donna, Hynd, Moyra, Janeczko, Adam, Jeffrey, Sally, Kinsey, Tony, Kummur, Yuvaraj, McIntosh, Karen, McKenna, John, Mclaughlin, Maria, Millington, Ryhs, Murphy, Emma, Parker, Kris, Reevell, Tom, Robertson, Fiona, Shankey-Smith, Will, Slorach, Colum, Szelei, Tamas, Warnock, Geoff, Watson, Stuart, Alston, Peter, Geddes, Murray, McLellan, Stuart, Allen, Eireann, Birnie, Karen, Brown, Kirsteen, Critchley, Julia, Cullen, Margaret, Eros, Alex, Forbes, Callum, French, Helen, Hall, David, Hetherington, Jonathan, Kellner, Maximiliane, Kelly, Keith, Khaled, Hiba, Mantle, Damien, McLenachan, John, Midgley, Susan, Nimmo, Susan, Ordys, Bart, Phelan, Hannah, Roddam, Philip, Shaw, Louise, Smith, Carolyn, Steel, Elizabeth, Stuart, Robert, Sturrock, John, Waite, Alasdair, Waterson, Fraser, Watson, Hannah, Wood, Elizabeth, Schraag, Stefan, Boyd, Elizabeth, Jain, Surabhi, Matthews, Elaine, Rappai, Geejo, Barr, Catriona, Stewart, Michael, Christie, Sharon, Smith, Tim, Arrow, Kate, Austin, Pauline, Chapman, Susie, Little, Jonathan, Malein, William, Sadler, Amy, Younger, Rhona, Reavley, Caroline, Allan, Katy, Ashok, Vignesh, Boroojeny, Ayda Borjian, Cutts, John-Paul, Faulds, Fiona, Fernie, Mark, Gadre, Amit, Gately, Tom, Haddon, Richard, Induruwage, Lalani, King, Siobhan, Liddle, Sian, Mallett, Paul, Mehotra, Saurabh, Ali, Inthekab Mohammed, Morris, Rachel, Nunn, David, Ferraro, Rocio Ochoa, Padhi, Pulak, Prusack, Ewa, Quak, Edmund, Singleton, Georgina, So, Kin, Stolady, Daniel, Welch, Drew, Whitear, Michael, Wilkinson, Kathy, Wu, James, Yusaf, Alex, Kakodkar, Prashant, Ghoneim, Hoda Abou, Balliston, Sara, Dudgeon, Lucy, Idris, Muna Elsheikh, Karattuparambil, Juneenath, Nanda, Lohita, Raithatha, Bhavesh, Saad, Mahmood, Spimpolo, Jenny, Titinchi, Linda, Wilson, Julie, Winstone, Ulrika, Martindale, Sarah, Cameron, Ewen, Fenner, Lynn, Hartford-Beynon, Jake, Mooney, Iain, Mundy, Charlotte, Rhidian, Rhys, Scutt, Sophie, Todd, Anna, Graham, Fiona, Ashton, Amy, Cooper, Theresa, Davidson, Katherine, Eapen, Suresh, Crowther, Hannah, Hindmoor, Claire, McSkeane, Anna, Mostafa, Mahamed, Mudimadagu, Gururaj, Rice, Polly, Wilson, Antoinette, Henry, Garry, Hollister, Nigel, Hunt, Jane, Isaac, Amanda, Morris, David, Paredes-Guerra, Antonio, Pass, Katherine, Paul, Martin, Rait, Kiran, Rousseau, Guy, Shacklock, Emma, Skinner, Amanda, Stancombe, Lucia, Thomson, Laura, Nutt, Christopher, Wright, Geoffrey, Holland, Johnny, O'Neill, Orla, Sengottaiyans, Arun, Mitra, Atideb, Garg, Sanjeev, Adams, Jonathan, Aiyedun, Temitope, Ali, Hani, Biuk, Sahar, Bond, Bryany, Cheeseman, Michelle, Clayton, Mark, Cottam, Lisa-Jayne, Dent, Kathy, Evans, Elizabeth, Evans, Sandra, Goodhand, Hannah, Green, Karen, Hatton, Jonathan, Hill, Joanne, Hutchinson, Dorothy, Jacob, Shibu, Joseph, Renjith, MacNally, Laura, Mann, Jason, McTaggart, Virginia, Newton, Maria, Pearson, Sandra, Rayet, Jaspreet, Saunders, Rebecca, Saxena, Sandeep, Venkatesh, Hemamangala, Whotton, Nikita, Ezihe-Ejiofor, Ada, Barot, Hemangini, Bridger, Hayley, Elhallous, Shady, Ghafoor, Rizana, Manhas, Vitul, Patil, Tanmay, Sadavarte, Nitin, Tharmalingam, Bhamini, Pritchard, David, Bage, Jean, Higgin, Sarah, Krishnaier, Asokan, Neilly, Esther, Rayappu, Sean, Siaw, Chye, Songaile, Ilma, Standen, Peter, Suresh, Narayanan, Weston, William, Williams, Lynne, Yuchen, Jiang, Alagar, Ravi, Taylor, Adrian, Matata, Claire, McCrossan, Roopa, Robertson, Andrew, Shekar, Priya, Stoker, Wendy, Turnbull, Elizabeth, Watkinson, Clare, Worthy, Stephen, Yates, Bryan, Ignatov, Dancho, Davies, Matthew, Abdu, Ayman, Banni, Donata, Bowyer, Helen, Brooks, David, Buhmann, Ulf, Christenssen, Victoria, Collins, James, D'Sa, Aaron, Forde, Steven, Groves, Alice, Hosahalli, Jyothi, Hunt, Lauren, Koshy, George, Lee, Robyn, Martin, Susan, McKnight, Angus, Murphy, Piers, Nash, Henry, Nkanang, Bassey, Oracki, Pamela, Pauley, Tara, Pope, Alan, Samanta, Romit, Sgardelis, Panagiotis, Stocks, Tom, Vaitheeswaran, Sivaprakash, Verma, Priya, Vrazhalska, Madlena Ivanova, Weisz, Mike, Moppett, Iain, Arunachalam, Subha, Begum, Zorba, Bhangu, Sonia, Bown, Gemma, Chana, Avninder, Chhaniyara, Puja, Constable, Natalie, Delme, Luff, Fenner, Helen, Griffith, Oliver, Hackett, Stephen, Hewson, David, Inkpin, Kristofor, Jones, Richard, Kirkdale, Richard, Lyons, Ian, Mandal, Arnab, Mehrotra, Prerna, Murphy, Martin, Pearce-Smith, Alison, Priestley, Martin, Pyke, Shirley, Rasoli, Sonia, Sharma, Suneal, Squires, Gemma, Tsim, Peter, Veitch, Jonathan, Bond-Smith, Giles, Kay, Olivia, Siviter, Richard, Allen, John, Baxter, Linden, Beer, Sally, Bernardo, Mariana, Coles, Holly, Cudlip, Jo, Devries, Talitha, Duggleby, Phil, Espinosa, Alexis, Fitzgibbon, Karina, Galente, Joao, Georgiou, Domonique, Ghosh, Soumi, Hingley, Nicholas, Kingan, Ryan, Levett, Chris, Martinez, Jose, Mattin, Alex, Moore, Anna, Morrish, Samuel, Nash, Amy, Patel, Tejuswi, Roe, Cieron, Thwaites, Victoria, Wali, Anuj, Watterson, Dafydd, Charlotte Yates, Anna Wilson, Gimenez, Marc, Boltres, Anita, McClean, Rebecca, Papadopoullos, Sam, Teh, Elena, Webb, Stephen, Brammar, Andrew, Humphreys, Joanne, Alibhai, Moiz, Alston, Daisy, Cohen, Jolyon, Coleman, Laura, Davies, Simon, Dervin, Dionne, Dooley, Rebecca, Drummond, Andrew, Findlay, Douglas, Fleming, Naomi, Hammoud, Yazzim, Hussain, Sanniah, Irwin, Katy, Javed, Asad, Kent, Linda, Lock, Lorraine, McSorland, Denise, Meadows, Alison, Mulligan, Paula, Nichols, Wendy, O'Callaghan, Maria, Ogor, Jonathan, Poole, Joanna, Ryder, Geoffrey, Shakoor, Akmal, Teo, Wei, Minto, Gary, Adshead, Stephen, Anderson, Helen, Carpenter, Adam, Clelland, Stuart, Datar, Priya, Elloway, Esme, Holl, Matt, Hulbert, Aidan, Humphreys, James, Hyams, Ben, McAleer, Sam, Newmarch, Mary, Notman, Holly, Patrick, Abigail, Perham, Anna, Pitman, Catherine, Reed, Fiona, Sampson, Paul, Smith, Hannah, Spinney, Sam, Toms, Nina, Warrener, Tim, Girgis, Michael, Barcraft-Barnes, Helena, Camsooksai, Julie, Colvin, Carolyn, Davies, Jack, Hamilton, Alex, Linton, Fiona, Nussbaum, Greg, Patch, Sarah, Simpson, Diane, Tbaily, Lee, Bain, James, A'Court, Alicja, Barr, Emma, Blethyn, Kate, Craig, Thomas, Cutler, Hugh, Davies, Jenny, Fry, Rebecca, Hawes, Elizabeth, Jenkins, Nicholas, Knight, Martin, Restall, David, Stubbs, Matthew, Sutherland, Angus, Swarbrick, Claire, Wilson, Robin, Winwright, Paul, Hamilton, Kevin, Adams, Anne, Allen, Orlanda, Boampomaa, Marilyn, Boniface, Anna-Marie, Coe, Robert, Daniel, Amelia, Finn, Joanne, Gill, Issac, Griffiths, Huw, Hackney, Joanna, Han, Ruth, Hare, Edward, Rintoul, Edward, Shpuza, Ervin, Smith, Ruth, Staines, Nikki, Suppiah, Puvan, White, Tracey, Pearson, Darcy, Cracknell, Ben, Farrell, Nadine, Hermanowski, Jane, Hodgson, Ruth, Hoskins, Toby, Jones, Rhiannon, Keable, Sam, Rosbergen, Melissa, Giles, Julian, Dawes, Thomas, Green, Ben Eden, Pottinger, Gail, Weller, Debbie, John, John, Burgess, Lisa, Denton, Jean, Done, Alaine, Edwards, Jayne, Garrett, Theresa, Gilla, Rajesh, Griffith-Norris, Samantha, Jones, Teresa, Linklater-Jones, Barbara, Nicholas, Claire, Owen, Sara, Perkins, Charlotte, Rowlands, Tessa, Steen, Julie, Turner, Sarah, Wales, Johanna, Woolley, Carol-Ann, Hormis, Anil, Collier, Dawn, Dixon, Kathryn, Gardner, Michael, Murray, Vicky, Soar, Harry, Walker, Rachel, Yaruk, Shifa, Yarwood, Daniel, Dill-Russell, Patrick, ruthy Arumugam, Bird, Georgina, Bleasby, Nichola, Chater-Lea, Peter, Craig, Emma, Davies, George, Foxton, Julie, Gilfillan, Helen, Jerram, Keelan, Kudsk-Iversen, Søren, Lee, Rebecca, Livesy, John, Mohabir, Amanda, Morris, Katherine, Raffles, Mike, Smith, Annika, Wang, Huiqi, Craig, James, Barratt, Nina, Bates, Andy, Bokor, Norbert, Cranshaw, Julius, Dominguez, Sergio, Fraine, Annette, Green, Richard, Molloy, Katie, Penny, Christina, Pitts, Sally, Purandare, Laura, Rabbi, Taslima, Serrano, Monica, Stoycheva, Tina, Vamplew, Luke, Williams, Steve, Berry, Julian, Adams, Benita, Bean, Sarah, Burt, Karen, Devooght-Johnson, Nicki, Hammonds, Fiona, Nicholls, Tom, Rowe, Michelle, Summers, Jessica, Ward, Olivia, Wroath, Belinda, Young, Gabbie, Matthews, Cathryn, Crosbie, Gearoid, Dunn, Alex, Eddy, Sara, Garcia, Lynda, Garwood, James, Green, Adam, Gupwell, Karin, Jones, Nicola, Marriott, Suzie, Masood, Mohammad, Mazzola, Francesca, McEvoy, Evanna, Ng, Yang, Park, Linda, Pauling, Stephanie, Potter, Alison, Renton, Caroline, Samways, Adam, Sibley, Pauline, Stead, Jenny, Thorpe, Kevin, Turner, Elizabeth, Walter, Michelle, Windsor, Kevin, Jha, Rajeev, Hooker, Nicolas, Kidel, Carlos, Abayalingam, Mayavan, Boulding, Richard, Coakley, Philip, Elahi, Noor, Helder, Filipe, Hilton, James, Joshi, Kunal, Kaur, Rupinder, Male, Victoria, Naji, Saqib, Pinto, Manuel, Rajendran, Yohinee, Save, Manjeet, Smith, Megan, Spence, Emily, Tang, Sophie, Urwin, Thomas, Wittenberg, Marc, Yan, Ruoling, Williams, Colin, Ardeshna, Arjun, Bamford, Peter, Hagyard, Sarah, Johnson, Patrick, McMonagle, Martina, Morris, Hayleigh, Murphy, Thomas, Papadopoulos, Stavros, Simpson, Emma, Smith-Williams, Jonathan, Vyapury, Vin, Juneja, Rohit, Black, Ethel, Eeles, Alex, Elliot, Justine, Jhanji, Shaman, Knoetze, Reynard, McCanny, Jamie, Oswald, Lauren, Roderick, Ellie, Gunning, Paul, Siddaiah, Narendra, Balachandar, Krishna, Bhimarasetty, Chandra, Bird, Laura, Blunt, Conny, Da Silva, Egidio, Darbyshire, Mark, Echaveznaguicni, Irene, Girgis, Youssef, Goodman, Martin, Gowda, Dinkar, Gowni, Rajashekar, Hayes, Melony, Jackson, Natalie, James, Anitha, Jayapal, Rekha, Jones, Claudette, Leung, Enid, Minhas, Simran, Mubarak, Mona, Muniyappa, Sudeshkumar, Nassa, Zehrin, Neal, Tom, Nyangoni, Kudakwashe, Panchakshariah, Suresh, Philpott, Bethany, Pinner, Craig, Pygall, Daniel, Rangaiah, Manamohan, Rao, Anil, Rea, William, Shellard, Richard, Shinner, Guy, Sutherland, Tony, Tharakan, Liza, Thomas, Sue, Travasso, Betty, Venkatesh, Pyda, Wortley, Dionne, Dickinson, Matthew, Benoliel, Sophie, Doyle, Nanci, Marriott, Cheryl, Martin, Sarah, Montague, Laura, Penhaligon, Kate, Saha, Rita, Santhirapala, Ramai, Suntharanathan, Lushani, Wakeford, Nichola, Webb, Carly, Winterbottom, Toby, Jordan, Lesley, Aldridge, Matt, Bolton-Hill, Clare, Cook, Prof Tim, Kangesan, Inthu, Kettley, Laura, Mew, Edward, Penketh, James, Quinn, Eleonore, Scholes, Sam, Uppugonduri, Sreekanth Rayalu, Allen, Lara, Lyndsay Bibb, Jill Brown, Busby, Charlotte, Katherine Cheshire, Davis, Matron Beryl, Denyer, Rebecca, Julie Edwards, Gardiner, Laura, Haque, Shamim, Icke, Julia, Jones, Katherine, Donna McIntosh, Mandy Oakley, Prasad, Linda, Victoria Roberts, Smallwood, Andrew, Tammy Smith, Stelfox, Lucy, Angela Stevens, Angela Willberry, Pratt, Oliver, Chincholkar, Mahindra, Darwin, Leanne, Dearden, Joy, Flowerdew, Adele, Harrison, Louise, Hartley, Robert, Ingham, Andrea, Jones, Ben, Lee, Stephanie, Longdon, Elizabeth, Marsden, Tracy, Meats, Kirsty, Michael, Angiy, Norwood-Green, Drew, O'Loughlin, Victoria, Owen, Holly, Patel, Manju, Perez, Jane, Whiston, Jessica, Wood, Andrea, Williams, Simon, Billingham, Chloe, Clarke, Caroline, Holmwood, Xantha, Knighton, Melba, Sands, Becky, Stevens, Paul, Strong-Sheldrake, Sophia, Taylor, Matthew, Rambhatla, Mrutyunjaya Rao, Brodier, Elizabeth, Choudhry, Ozerah, Choudhry, Usman, Fitzmaurice, Bethany, Hulme, Jonathan, Kannan, Santhana, Mak, Kay Anne, Namih, Miriam, Rajdev, Bharati, Rambhatla, Swetha, Reilley, Stuart, Rice, Rebecca, Sethia, Nalini, Smith, Katy, Wakhle, Rahul, Walmsley, Chris, Wrench, Ian, Agyemang, Michael, Bell, Elizabeth, Bird, Sarah, Briscoe, James, Cruickshanks, Andy, Drinkwater, Jake, Eggleston, Sam, Elms, Henry, Hammon, Laura, Harris, Meredith, Harrison, Christopher, Hirst, Claire, Housley, Kay, Kapoor, Krish, Kibutu, Faith, Kilner, Beverly, King, Emily, Kirk, Emily, Marshall, Esme, Mazzone, Paolo, Middle, Janet, Milner, Leanne, Mitchell, Adam, Morris, Becky, Mudd, Alexandra, Needham, Matthew, Nicholas, James, Penson, Rob, Perfitt, Joel, Pinkerton, Mark, Recto, Mayeth, Rehnstrom, Maria, Riley, Catherine, Ryan, Lorna, Smith, Jennie, Strong, Samantha, Thornley, Helen, Tookey, Bethany, West, Daniel, Whitaker, John, Willcock, Sarah, Willoughby, Shay, Wright, Jane, Jones, Paul, Abbott, Riquella, Bacon, Lisa, Godden, Christopher, Howe, David, Loughlin, Angela, Moore, Helen, Passey, Samuel, Rodgers, Rebekah, Foley, Paul, Hagan, Samantha, Marcus, Simon, Gardner, Irene, Haslam, Zena, Morrison, Moira, Obeysekera, Chai, Porter, Kim, Terrett, Helen, Henning, Jeremy, Baillie, Kirsty, Buchanan, Ella, Cain, Martyn, Colling, Kerry, Duarte, Raquel, Gibb, Chris, Hynd, Ryan, Irvine, Victoria, Lyons, Rob, Middleton, Karoline, Razaque, Usman, Sheikh, Faisal, Tabiner, Tariq, Frey, Christian, Brown, Carly, Clifford, Gayle, McKee, Madeleine, Stidolph, Beverley, White, Emert, Campbell, Bridget, Mason, Sophie, Parsons, Penny, Santana-Vaz, Natasha, Stagg, Camilla, Shah, Nirav, Barnes, Veronica, Bedoes, Penny, Clarke, Jonathan, Crichton, Robert, Das, Madhurima, Davies, Paul, Farrah, Helen, Hegarty, Aoife, Howlett, Luisa, Kleine-Brueggeney, Maren, Ma, Samson, Marsh, Veronica, McAndrew, Katherine, Mellinghoff, Johannes, Oscier, Christopher, Ryan, Christine, Smee, Elizabeth, Thurairasa, Dushanthi, Goel, Vandana, Adeney, Christopher, Behl, Sanjay, Chadwick, Karen, Coleman, Thomas, Davies, Claire, Dealing, Sharon, Elwood, Jamie, Fadden, Emma, Gillies, Stella, Kennedy, Tom, Miller, Thomas, Morton, Simon, Reilly, Rebecca, Smyth, Sue, Syratt, Thomas, Welfare, Emma, Thomas, Elizabeth, Awolesi, Jennifer, Bennett, Hannah, Bradshaw, Elizabeth, Crabtree, David, Duraman, Lauren, Hughes, Kerry, Kirk, Sarah, Leonard, Dee, Stoeter, Rachel, Parrington, Simon, Andorka, Matyas, Ang, Kingsin, Bailey, Linda, Brooks, Stephanie, Chiu, Oon, Collins, Sally, Jack, James, Knight, Harry, Lynn-Smith, Anastasia, Mackenzie, Matt, Maher, Sarah, Nimako, Louise, Sangaralingham, Siva, Sanusi, Seliat, Weller, Samantha, Willard, Elizabeth, Kulkarni, Anand, Carroll, Peter, Clark, Martyn, Coulding, Martina, Denman, Elizabeth, El Habishi, Mohyman, Haywood, Patrick, McConniffe, Jane, McCormick, Jacqueline, Melachuri, Krishnakar, Philip, Evelyn, Ridgway, Stephanie, Savill, Heather, Sharif, Kamal, Vere, Joanne, Harris, Stephen, Coombs, Alex, Darch, Flora, Doble, Patricia, Foot, Jayne, Gillett, Chris, Judd, Thomas, Moss, Alison, Pawley, Corinne, Tait, Moira, Whitcher, Alison, Wood, Natalie, Montgomery, Jane, De Selincourt, Gabrielle, Fitzell, Pauline, Flower, Katie, Horan, Kathleen, Hulance, Bianca, Mercer, Pauline, Shaw, Sarah, Webber, Robin, Kakkar, Manish, Joachim, Suganthi, Aggarwal, Seetal, Ali, Amr, Ang, Boon, Bhardwa, Vishnu, Deamer, Wendy, Filby, Lorna, Fletcher, Jo, Fombon, Felix, Gawley, Shannon, Gosavi, Chandrakant, Hindle, Julia, Lawrence, Tara, Maher, Robert, Moore, Samantha, Netherton, Kimberley, Orasanu, Teodora, Poimenidi, Evangelia, Potter, Louise, Ranasinghe, Niyesa, Ribeiro, Lester, Ruth, Thoy, Butler, Susie, Sutton, Tim, Thomas, Issy, Veluvolu, Divya, Walker, Thomas, Wariyapola, Charindri, Zaheer, Lail, Luoma, Valpuri, Ferguson, Catriona, Stewart, Adrienne, Bapat, Smita, Bose, Gahan, Bugo, John, Campbell, Marta, Cervi, Elizabeth, Ciechanowicz, Sarah, Coathup, Rachel, El-Wahab, Niveen, Frith, Claire, Gill, Preea, Gray, Martin, Luoma, Astri, Mehta, Sachin, Murali, Mayur, Mussad, Asya, Parker, Laura, Patch, Josh, Perella, Paolo, Robson, Emily, Setty, Thunga, Vieira, Filipe, Wall, Josh, Witby, Jon, Zghaibe, Wael, Zhang, Sheldon, Merron, Stephen, Abano, Nenette, Barnett, Loretta, Barry, Adrian, Birks, Pamela, Brade, Judith, Butler, Adrian, Carpio, Racquel, Colclough, Viv, Eaton, Katrina, Edwards, Carol, Emery, Lisa, Finney, Kay, Gallagher, Susan, Ghatge, Satyajeet, Grocott, Jeanette, Hall, Amanda, Hardwick, Alison, Harrison, Anne, Hendy, Susan, Hiden, Joanne, James, Alex, Jeganath, Vijay, Kumar, Rahul, Lord, Stephen, Lovatt, Rachel, Lyjko, Susan, Maguire, Holly, Marsden, Mia, Mehta, Venu, Mishra, Rajeev, Mittal, Rohit, Moores, Andrew, Nalwaya, Pramod, Omeara, Matthew, Orosz, Sandor, Patel, Nehal, Pattison, Nicola, Ponce, Ida, Puttapa, Ashok, Rajamanickam, Tamilselvan, Rao, Nagaraj, Remegoso, Alda, Rhodes, Rochelle, Rooney, Angela, Sadler, Emma, Singh, Permendra, Soon, Wai, Tomlins, Simon, Umbarje, Kanchan, Vallabhaneni, Murali, Varquez, Resti, Wain, Jill, White, Sorana, Willetts, Elizabeth, Williams, Benedict, Wood, Andrew, Washington, Stephen, Anipindi, Sujata, Aston, Jennifer, Bradley-Potts, Joanne, Butler, Ian, Cunningham, Jennifer, Duncan, Alastair, Garrard, Hywel, Haslam, Daniel, Kirk, Danielle, McCormick, Richard, McEvoy, Michael, Mistry, Sara, Ormandy, Danielle, Sharp, Tracy, Song, Andrew, Williamson, Georgina, Young, Francis, Tasker, Laura, Bailey, Elizabeth, Baker, Roisin, Bamford, Amy, Bergin, Colin, Blackburn, Julia, Bodo, Kinga, Carrera, Ronald, Cooper, Lauren, Despy, Liesl, Ellis, Karen, Foster, Morgan, Garner, Sharon, Harkett, Lyndon, Harkett, Samantha, Ip, Peter, Lay, Frances, Liu, Hon Sum, Mee, Laura, Nazir, Samir, Osbourne-Wylde, Jacob, Patel, Krupali, Pope, Martin, Reeves, Emma, Sahni, Melanie, Small, Charlotte, Spooner, Brendon, Spruce, Elaine, Whitehouse, Arlo, Wharton, Nicholas, Alexander, Rachel, Ashford, Amy, Aspinall, Rebecca, Bateman, Richard, Bell, Matthew, Bennett-Britton, Jennifer, Bewley, Jeremy, Blanshard, Hannah, Bourdeaux, Christopher, Brook, Peter, Cain, Helen, Cameron, Claire, Cassells, Naomi, Chauhan, Nilesh, Clarke, Adrian, Cockroft, Melanie, Cohen, Alan, Collins, Joanna, Cominos, Timothy, Craven, Rachael, Davies, Ian, Dolling, Sarah, Dowse, Claire, Driver, Kate, Duffen, Adam, Dunn, Sarah-Jane, Earnshaw, Charlotte, Forrest, Frances, Freshwater-Turner, Dan, Gardner, Issie, Gibbins, Matthew, Gibbison, Ben, Gleeson, Suzanne, Gould, Timothy, Govier, Matthew, Gupta, Benjamin, Hadfield, John, Harvey, Nicola, Henderson, Sophia, Herbert, Lara, Hillier, James, Hood, Elizabeth, Howes, Ben, Howes, Helen, Hughes, Sian, Jackson, Kathryn, Jacobs, Toby, Jenkins, Emma, Jenkins, Ian, Johnstone, Alistair, Jones, Lydia, Jones, Rebecca, Joshi, Natasha, Kamalanathan, Kajan, Kellie, Neil, Kidd, Lawrence, Kinsella, Mike (Stephen), Knight, Thomas, Leslie, Rebecca, Linter, Stephen, Lovell, Tim, Martin, Matthew, McHugh, Ursula, McIndoe, Andrew, McKendry, Rachel, Middleditch, Alexander, Miles, Edward, Milne, Lesley, Molyneux, Mat, Muchatuta, Neil, Murphy, Ruth, O'Higgins, Fran, Oglesby, Kieran, Pachucki, Marcin, Paoloni, Claudia, Patel, Nishita, Patton, Catherine (Katie), Paulich, Skylar, Pearson, Annabel, Pickering, Anthony, Platt, Martin, Pope, Charlie, Pryn, Steve, Ranjan, Amit, Rasburn, Neil, Ray, Andrew, Rivers, Jonathan, Rooney, Kieron, Ryder, Ian, Sanders, Sarah, Sasi-Kumar, Kavita, Scott, Liam, Scrutton, Mark, Searles, Chloe, Self, James, Shah, Sanjoy, Sheils, Mark, Shipway, Toby, Short, Heather, Simmonds, Lauren, Smith, Daniela, Soodan, Anjali, Steeds, Charlotte, Sweet, Katie, Syme, Phoebe, Thomas, Matthew J., Tomkins, Sally, Underwood, Susan, Wagstaff, Adrian, Watson, Paul, Webster, Denise, Welham, Katie, Whaley, Anne, Williams, Helen, Wilson, Hannah, Winton, Anoushka, Woodward, Thomas, Worthington, Jeanie, Younie, Stuart, Bradbury, Carol, Auldin, Mohammad, Bosworth, Kate, Choksey, Falguni, Dudkowsky, Bernice, Elton, John, Evans, Gail, Grove, Charlotte, Ingram, Clare, Kelly, Andrew, Lax, Peter, Lynes, Elena, Madden, George, Mistry, Vinesh, Molitor, Timothy, Morgan, Catherine, Morris, Natalie, Pallister, Emily, Patel, Pooja, Ragothaman, Vijay, Ramm, Katie, Robinson, Ben, Sharma, Meghna, Shuttleworth, Daniel, Vaidyanath, Chandrashekhar, Warren, Jen, Wong, Rachel, Lau, Gary, Conway, Hannah, Majeed, Adeel, Parmar, Jaina, Rana, Meenal, Yusuff, Hakeem, Rimmer, Corinne, Abdelrhamen, Wael, Allison, Kathryn, Burns, Karen, Cahill, Nichola, Clark, Jon, Donaldson, Hannah, Heseltine, Nick, Mackenzie, Nicola, McArthur, Carol, Moreland, Neil, Shohelly, Sharmin, Thatcher, Hilary, Tran, Steven, Walker, Catriona, Al-Rawi, Samar, Wakatsuki, Mai, Aarvold, Alice, Addy, Melissa, Ashfield, Georgina, Beauchamp, Nigel, Belcher, Alex, Bennett, Tom, Burgess, Victoria, Burton, Andy, Campbell, Matthew, Cruikshank, Ross, Cumpstey, Andy, Davies, Rhys, Ford, Chris, Ford, Renee, Hawkins, Lesley, Hendra, Tim, Huttley, Thomas, Jolly, Erica, Kalcheva, Nevena, Kennedy, Charlie, Lees, Jessica, Lowe, Richard, Martindale, Tim, McCormick, Sarah, McPhee, Hannah, Millinchamp, Fran, Muddanyake, Rahul, Osorio, Eduardo, Patel, Kiran, Pestell, Samuel, Phillips, Steve, Plumb, Jamie, Pratt, Thomas, Quartermain, Bert, Reeves, Rebecca, Robin, Sophie, Scully, Thecla, Sehgal, Anamika, Seifalan, Said, Shuttleworth, Suzanne, Siddique, Omar, Sleap, Esme, Smith, Victoria, Snooks, Richard, Solanki, Virginia, Timmons, Christina, Trimble, Alice, Tunney, Doug, Walker, Kat, Wee, Naomi, Wigley, James, Wilkins, Huw, Wong, Hanna, Wood, Laura, Yogya, Dinithi, Young, Ruth, Shanbhag, Sumant, Ameer, Farrukh, Finnity, Jonathan, Haddock, James, Hunt, Alex, Kuravi, Aditya, Lenehen, Fionnuala, McOwat, Lindsay, Naqvi, Asad, Richardson, Lisa, Siddons, Victoria, Charters, Seema, Jumani, Deepa, Bradley, Peter, Bubb, Laura, Chan, Rebekah, Connell, Lynne, Crone, Rachel, Davis, Hannah, Defeyter, Pascal, Evans, Alison, Howard, Ramdas, Prady, Helena, Rogers, Natalie, Roughley, Lindsay, Whittle, Helen, Zeinali, Daniel, Cherian, Vinanti, Latif, Muhammad Usman, Bajwa, Maqsood, Guy, Jonny, Guz, Krzysztos, Iftikhar, Nauman, Iwanicka, Beata, Khan, Mujeeb, Love, Anna-Marie, Montgomery, Celia, Mulvany, Stephen, O'Kane, Emma, O'Kane, Sinead, Siddiqui, Mansoor, Small, Cathal, Subhani, Shaik, Dana, Emily, Kennedy, Richard, Amey, Isobel, Ashton, Hilary, Baird, Yolanda, Bushell, Caroline, Chadbourn, Indra, Cohen, Merle, Finlay, Emma, Gilbert, Jeanette, Helm, David, Lewis, Carla, Macallan, Jenny, Margalef, Jordi, Martins, Nic, Metiu, Gabi, Moore, Sally, Rose, Hannah, Standley, Tom, Page, Valerie, Bakonyi, Tomas, Ben-Nathan, Simon, Claridge, Melanie, Evans, Jackie, Gardiner, Harriet, Kantsedikas, Ilya, Lachana, Ann, Makker, Ratna, Markwell, Karen, Merrill, Colin, Mukerjee, Prasun, O'Donohoe, Lynn, Oglesby, Fiona, Osbourne, Laura, Parker, Beena, Passaro, Emelia, Russell, Katherine, Shah, Sneh, Sundayi, Saul, Walker, Elaine, Zhao, Xiao, Hosdurga, Guru, Cotterill, Donna, Crowther, Nicola, Dymond, Harvey, Ratcliffe-Law, Thomas, Saunders, Glenn, Saunders, Thomas, Gopal, Vijayakumar, Ahmed, Sajjad, Ali, Abdalla, Crawford, Sarah, De'Ath, Clare, Humphreys, Sally, Swanevelder, Carin, Yap, Yeng, Silk, Jane, Adeniba, Rashidat, Armstrong, Richard, Egole, Osi, Fan, Karen, Gilbert, Kayleigh, Gould, Laura, Hickman, John, Long, Fei, Pahary, Sheik, Reichman, Michelle, Simpson, Kathryn, Singaravelu, Suresh, Ahmed, Dabeeruddeen, Brailsford, Fiona, Bridge, Laura, Collis, Lauren, Jacob, Reni, Jones, Cathy, Kirrage, Amanda, Lowe, Jessica, Mullen, Joanne, Prenter, Andrew, Sarao, Sarbpreet, Sharpley, David, Wankhade, Kavita, Persad, Cindy, Burtenshaw, Andrew, Blyth, Kate, Corcoran, Felicity, Davis, Caroline, Dolan, Rachel, Hussain, Nageena, Pearson, Emma, Pierson, Anna, Poyntz, Victoria, Thrush, Jessica, Wollaston, Alex, Wollaston, Julie, Clements, Paul, Biswas, Arindam, Clayton, Sarah, Clayton, Thomas, Cochrane, Naomi, Duell, Kirsty, Evans, James, Gaskell, Mark, Heaton, Dianne, Heaton, Linzi, Hill, Claire, Killen, Ruth, Latham, Sandra, McIntosh, Gemma, Moore, Chris, Parkinson, Val, Pemberton, Nicola, Robinson, Matthew, Sawyer, Alastair, Sykes, Isabelle, Taylor, Tracey, Tierney, Caroline, van de Snepscheut-Jones, Katja, Wade, Emily, Wahid, Mohammed, Wang, Henry, Williams, Claire, Wu, Dominic, Yadagiri, Manjula, Zabauski, Dmitry, Troth, Laura, Andrews, Eleanor, Bains, Ranjit, Beard, Laura, Birch, Janine, Britton, Rachael, Salmon, Mike, Vassell, Elizabeth, Kubisz-Pudelko, Agnieszka, Allen, Jamie, Allison, Joanna, Baird, Andrew, Gregory, Rob, Luckhurst, Hannah, Mairs, Rebecca, Marshall, Ben, Pippard, Lucy, Pitt-Kerby, Tressy, Savva, Andrew, Walkden, Graham, Weegenaar, Celly, Chandler, Ben, Kanakaraj, Muthuraj, Chamberlain, Andy, Dyer, Simon, Elliott, Kerry, Forshaw, Greg, Furness, Rosie, Gibson, Andy, Howe, Laura, Kent, Sarah, Rodgers, Alicia, Straughan, Ben, Temlett, Emma, Whitwell, John, Wong, D.J.N., Harris, S.K., and Moonesinghe, S.R.

Published
2018
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29. The repair of DNA breaks in Escherichia coli and analysis of the bacterial recombination protein RecN

Author

Wood, Stuart Robert

Subjects
572.8, QU Biochemistry
Abstract

A DNA double-strand break is an exceptionally toxic lesion that threatens the structural and functional integrity of the genome. In this thesis the repair of DSBs was investigated using the bacterium Escherichia coli, which repairs DNA breaks almost exclusively by homologous recombination. The studies described focus on the repair of damage induced by reactive oxygen species, but especially on the RecN protein, which is associated specifically with the repair of double-strand breaks. The RecN protein is highly conserved across bacterial species and in E. coli has been identified as a key factor in the repair of DNA breaks. In this thesis three RecN homologs were analysed. RecN from Haemophilus influenzae is shown to be capable of replacing the functions of E. coli RecN in vivo. However, homologs from Aquifex aeolicus and Bacteriodes fragilis cannot do so. Biochemical analysis of all three RecN homologs was undertaken. The H. influenzae RecN and A. aeolicus RecN were shown to have weak ATPase activity and an ability to interact with single-stranded DNA. ATPase deficient mutants of the RecN proteins were created and used to demonstrate the functional importance of the ATP hydrolysis. In the case of E. coli and H. influenzae, the ATPase defective mutants failed to function in vivo. In vitro, the ATPase deficient H. influenzae RecN mutant and a similar mutant of A. aeolicus RecN failed to interact with single-stranded DNA. These data are discussed in terms of a relationship between RecN and the structural maintenance of chromosome family of proteins. Finally, a model for RecN activity is presented based on those developed to explain the function of structural maintenance of chromosome proteins and the new data presented here. In this model, RecN is suggested to trap DNA molecules holding a break site and repair template in close proximity, facilitating the repair of DNA breaks by homologous recombination. The possibility of RecN acting as a global, damage induced cohesin is also discussed.

Published
2009

31. P517: SURVIVAL OUTCOMES WITH CPX-351 VS 7 + 3 BY BASELINE BONE MARROW BLAST PERCENTAGE IN OLDER ADULTS WITH NEWLY DIAGNOSED HIGH-RISK OR SECONDARY ACUTE MYELOID LEUKEMIA: A 5-YEAR FOLLOW-UP STUDY

Author

Ritchie, Ellen, primary, L. Lin, Tara, additional, F. Newell, Laura, additional, K. Stuart, Robert, additional, Solomon, Scott, additional, Stone, Richard, additional, Schiller, Gary, additional, Wieduwilt, Matthew, additional, Amy Ryan, Eileen, additional, Dronamraju, Nalina, additional, Lancet, Jeffrey, additional, and Cortes, Jorge, additional

Published
2023
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34. New aromatic annulation reactions and their application in total synthesis

Author

Flanagan, Stuart Robert

Subjects
547.6
Abstract

A new benzannulation reaction involving a tandem Horner-Emmons and Claisen condensation sequence was developed and applied to the syntheses of six arylnaphthalene ligands: taiwanin C, justicidin E, chinensin, retrochinensin, justicidin B and retrojusticidin B. The tin-mediated addition of aryl radicals to various electron-rich condensed heterocycles was also investigated, 5-Exo-trig additions of N-tethered aryl radicals to indoles were demonstrated and shown to be more efficient when the radical intermediate was flanked by substituents. Addition of aryl radicals to C-2 and C-3 of indoles, benzo[b]thiophenes and benzo[b]furans were also studied and the course followed found to be strongly influenced by the nature of the constituent heteroatom. When as cis-alkene was used to tether the arene to the heterocycle a 6-endo-trig radical cyclisation pathway was followed, leading to the corresponding polyaromatic system. A notable exception arose when the aryl radical was tethered to C-3 of a benzo[b]thiophene or benzo[b]furan. In such cases, an addition-elimination-reduction pathway dominated, yielding the corresponding 2-(2-naphthyl)-(thio)phenol. With an alkane or benzyl ether as the tether, cyclisations generally proceeded via 5-exo-trig addition of the aryl radical to the tethering carbon. However, with benzo[b]furans and N-acetyl indoles, C-3 tethered aryl radicals preferentially underwent 6-endo-trig addition to C-2 of the heterocycle in a reductive fashion. A total synthesis of demethylhomopterocarpin using this methodology is described.

Published
2003

36. The interplay between accretion, downsizing, and the formation of box/peanut bulges in TNG50.

Author

Anderson, Stuart Robert, Gough-Kelly, Steven, Debattista, Victor P, Du, Min, Erwin, Peter, Cuomo, Virginia, Caruana, Joseph, Hernquist, Lars, and Vogelsberger, Mark

Subjects
*MERGERS & acquisitions, *PEANUTS, *STELLAR mass, *MEASUREMENT errors, *GALACTIC evolution, *GALACTIC bulges
Abstract

From the TNG50 cosmological simulation we build a sample of 191 well-resolved barred galaxies with stellar mass |$\mbox{$\log (M_{\star }/\mathrm{M}_{\odot })$}\gt 10$| at z  = 0. We search for box/peanut bulges (BPs) in this sample, finding them in 55 per cent of cases. We compute |$\mbox{$f_{\rm BP}$}$|⁠ , the BP probability for barred galaxies as a function of M ⋆, and find that this rises to a plateau, as found in observations of nearby galaxies. The transition mass where |$\mbox{$f_{\rm BP}$}$| reaches half the plateau value is |$\mbox{$\log (M_{\star }/\mathrm{M}_{\odot })$}= 10.13\pm 0.07$|⁠ , consistent with the observational value within measurement errors. We show that this transition in |$\mbox{$f_{\rm BP}$}$| can be attributed to the youth of the bars at low M ⋆, which is a consequence of downsizing. Young bars, being generally shorter and weaker, have not yet had time to form BPs. At high mass, while we find a plateau, the value is at |$\sim 60~{{\ \rm per\ cent}}$| whereas observations saturate at 100 per cent. We attribute this difference to excessive heating in TNG50 due to merger activity and numerical resolution effects. BPs in TNG50 tend to occur in galaxies with more quiescent merger histories. As a result, the main driver of whether a bar hosts a BP in TNG50 is not the galaxy mass, but how long and strong the bar is. Separating the BP sample into those that have visibly buckled and those that have not, we find that fully half of BP galaxies show clear signs of buckling, despite the excessive heating and limited vertical resolution of TNG50. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Maternal Hypercholesterolemia During Pregnancy Promotes Early Atherogenesis in LDL Receptor-Deficient Mice and Alters Aortic Gene Expression Determined by Microarray

Author

Napoli, Claudio, de Nigris, Filomena, Welch, John S, Calara, Federico B, Stuart, Robert O, Glass, Christopher K, and Palinski, Wulf

Subjects
Genetics, Digestive Diseases, Nutrition, Cardiovascular, Atherosclerosis, Pediatric, 2.1 Biological and endogenous factors, Aetiology, Reproductive health and childbirth, Animals, Aorta, Arteriosclerosis, Body Weight, Cholesterol, Cholesterol, Dietary, Dietary Fats, Disease Models, Animal, Disease Progression, Expressed Sequence Tags, Female, Gene Expression Profiling, Gene Expression Regulation, Genetic Predisposition to Disease, Hypercholesterolemia, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, RNA, Messenger, Receptors, LDL, Sex Factors, Triglycerides, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundMaternal hypercholesterolemia during pregnancy is associated with markedly enhanced fatty streak formation in human fetal aortas and accelerated progression of atherosclerosis in normocholesterolemic children.Methods and resultsTo establish the causal role of maternal hypercholesterolemia in a genetically homogeneous murine model and to test the hypothesis that pathogenic events during fetal development result in persistent changes in arterial gene expression, female LDL receptor-deficient (LDLR(-/-)) mice were fed regular chow or high-fat diets supplemented with 0.075% or 1.25% cholesterol during pregnancy. Lesion sizes were determined in the aortic origin of their chow-fed offspring at 3 months. Maternal hypercholesterolemia more than doubled lesion sizes in male offspring (P1.7-fold. Quantitative PCR for one of these genes using RNA from individual mice yielded similar results. Comparative immunostaining for several of the above genes also indicated increased protein content in offspring of hypercholesterolemic mothers.ConclusionsThese findings establish an atherogenic effect of maternal hypercholesterolemia in genetically uniform mice and indicate that changes in aortic gene expression persist long after fetal exposure to hypercholesterolemia. In addition to elucidating pathogenic mechanisms initiated during fetal development, this approach may identify genes in morphologically normal arteries that influence the susceptibility to classical risk factors of atherosclerosis.

Published
2002

43. Pushing the Boundaries of Spacecraft Autonomy and Resilience with a Custom Software Framework and Onboard Digital Twin

Author

Jonathan Paxman, Robert Howie, Buchan, Stuart Robert Gibson, Jonathan Paxman, Robert Howie, and Buchan, Stuart Robert Gibson

Abstract

This research addresses the high CubeSat mission failure rates caused by inadequate software and overreliance on ground control. By applying a reliable design methodology to flight software development and developing an onboard digital twin platform with fault prediction capabilities, this study provides a solution to increase satellite resilience and autonomy, thus reducing the risk of mission failure. These findings have implications for spacecraft of all sizes, paving the way for more resilient space missions.

Published
2023

45. Synaptic interaction of hippocampal gabaergic neurones

Author

Cobb, Stuart Robert

Subjects
571.4, Hippocampus (Brain), Physiology, Mechanism of action, Synapses
Abstract

Current concepts of hippocampal circuitry assume a large population of excitatory principal neurones whose activity is largely governed by a network of local-circuit GABAergic interneurones. The diversity of hippocampal local-circuit neurones and their synaptic control over principal cell activity was investigated in vitro, in order to define their synaptic connections and functional roles. Single and dual intracellular recordings were made from local-circuit neurones and pyramidal cells in area CA1 of the rat hippocampal slice. Interneurones were tentatively distinguished from pyramidal cells based on their firing as well as their membrane properties. Intracellular labelling of recorded cells with the marker biocytin revealed a diversity of cell types based on differential dendritic and axonal morphology and synaptic connections. The physiological data revealed that all types of interneurone tested evoked inhibitory postsynaptic potentials (IPSPs) in simultaneously recorded pyramidal cells. The IPSPs had fast rise and decay kinetics and the ones tested pharmacologically, were mediated by GABAA receptors. Similarly, individual interneurones were also shown to innervate other local-circuit interneurones in addition to pyramidal cells, the evoked effects being qualitatively similar in both types of postsynaptic targets. The postsynaptic effect and functional role of one type of hippocampal interneurone, the basket cell, was investigated in greater detail. Basket cell-evoked IPSPs were reliable, but showed some frequency-dependent attenuation. Moreover, basket cell IPSPs were found to interact with intrinsic pyramidal cell conductances to elicit rebound depolarisations and facilitate action potential generation. More detailed investigation showed that basket and axo-axonic cells were particularly effective in entraining pyramidal cell firing and sub-threshold membrane potential oscillations. Through these powerfully tuned mechanisms, sub-types of local-circuit interneurone provide a powerful mechanism to synchronise the activity of pyramidal cells. These results demonstrate a remarkable diversity of GABAergic local-circuit neurones in the hippocampal CA1 area and suggest that specific subtypes of cell mediate different functions.

Published
1996

47. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations

Author

Lindsley, R. Coleman, Mar, Brenton G., Mazzola, Emanuele, Grauman, Peter V., Shareef, Sarah, Allen, Steven L., Pigneux, Arnaud, Wetzler, Meir, Stuart, Robert K., Erba, Harry P., Damon, Lloyd E., Powell, Bayard L., Lindeman, Neal, Steensma, David P., Wadleigh, Martha, DeAngelo, Daniel J., Neuberg, Donna, Stone, Richard M., and Ebert, Benjamin L.

Published
2015
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49. Testing for relics of past strong buckling events in edge-on galaxies: Simulation predictions and data from S$^{4}$G

Author

Virginia Cuomo, Victor P Debattista, Sarah Racz, Stuart Robert Anderson, Peter Erwin, Oscar A Gonzalez, J W Powell, Enrico Maria Corsini, Lorenzo Morelli, and Mark A Norris

Subjects
galaxies: bar, galaxies: bulges, galaxies: evolution, galaxies: photometry, galaxies: structure, Astrophysics - Astrophysics of Galaxies, Space and Planetary Science, Astrophysics of Galaxies (astro-ph.GA), FOS: Physical sciences, Astronomy and Astrophysics
Abstract

The short-lived buckling instability is responsible for the formation of at least some box/peanut (B/P) shaped bulges, which are observed in most massive, $z=0$, barred galaxies. Nevertheless, it has also been suggested that B/P bulges form via the slow trapping of stars onto vertically extended resonant orbits. The key difference between these two scenarios is that when the bar buckles, symmetry about the mid-plane is broken for a period of time. We use a suite of simulations (with and without gas) to show that when the buckling is sufficiently strong, a residual mid-plane asymmetry persists for several Gyrs after the end of the buckling phase, and is visible in simulation images. On the other hand, images of B/P bulges formed through resonant trapping and/or weak buckling remain symmetric about the mid-plane. We develop two related diagnostics to identify and quantify mid-plane asymmetry in simulation images of galaxies that are within 3{\deg} of edge-on orientation, allowing us to test whether the presence of a B/P-shaped bulge can be explained by a past buckling event. We apply our diagnostics to two nearly edge-on galaxies with B/P bulges from the ${\it Spitzer}$ Survey of Stellar Structure in Galaxies, finding no mid-plane asymmetry, implying these galaxies formed their bulges either by resonant trapping or by buckling more than $\sim 5$ Gyr ago. We conclude that the formation of B/P bulges through strong buckling may be a rare event in the past $\sim 5$ Gyr., Comment: Accepted for pubblication in MNRAS

Published
2022

50. Lower-Intensity CPX-351 + Venetoclax for Patients with Newly Diagnosed Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy: Post Hoc Analysis By Disease Risk Subgroups

Author

Lin, Tara L., primary, Baratam, Praneeth, additional, Stuart, Robert K., additional, Walter, Roland B., additional, Winer, Eric S., additional, Faderl, Stefan, additional, Chandrasekaran, Vijayalakshmi, additional, Chakravarthy, Divya, additional, Cheung, Ronald S., additional, and Pullarkat, Vinod A., additional

Published
2022
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