The emerging role of anti-CD25 directed therapies as both immune modulators and targeted agents in cancer

CD25 (also termed IL2RA) forms one component of the high‐affinity heterotrimeric interleukin 2 (IL2) receptor on activated T cells. Its affinity for IL2 and cellular function are tightly regulated and vary in different cell types. The high frequency of CD25 on the surface of many different haematological tumour cells is now well established and, apart from its prognostic significance, CD25 may be present on leukaemic stem cells and enable oncogenic signalling pathways in leukaemic cells. Additionally, high CD25 expression in activated circulating immune cells and Tregs is a factor that has already been exploited by IL2 immunotherapies for treatment of tumours and autoimmune disease. The relative clinical safety and efficacy of administering anti‐CD25 radioimmunoconjugates and immunotoxins in various haematological tumour indications has been established and clinical trials of a novel CD25‐directed antibody drug conjugate are underway

Buried (drift-filled) hollows in London – a review of their location and key characteristics

All data generated or analysed during this study are included in this published article (and its supplementary information files). For several features where the raw data are confidential contact the author, Amy Flynn, to seek permission.© 2020 The Author(s). This paper compiles new and existing information relating to features frequently referred to as drift-filled hollows located within London. The key aim of this paper is to update the article written by Berry (1979, ‘Late Quaternary scour-hollows and related features in central London’, QJEG, 12, 9–29, doi: 10.1144/GSL.QJEG.1979.012.01.03), producing a resource for both engineering projects and academic research. Fifty-four additional drift-filled hollows have been identified and their physical characteristics are tabulated where available information allows. A case study of the Nine Elms area is presented. The drift-filled hollows have been identified through examination and critical, quality assessment of historical borehole records, site investigation records, construction records and published articles. This enlarged dataset illustrates the high level of variability between features and, as a result, it is proposed that these features did not form due to a single process, but to differing processes.Engineering and Physical Sciences Research Council (EPSRC)

The glyoxal budget and its contribution to organic aerosol for Los Angeles, California, during CalNex 2010

Recent laboratory and field studies have indicated that glyoxal is a potentially large contributor to secondary organic aerosol mass. We present in situ glyoxal measurements acquired with a recently developed, high sensitivity spectroscopic instrument during the CalNex 2010 field campaign in Pasadena, California. We use three methods to quantify the production and loss of glyoxal in Los Angeles and its contribution to organic aerosol. First, we calculate the difference between steady state sources and sinks of glyoxal at the Pasadena site, assuming that the remainder is available for aerosol uptake. Second, we use the Master Chemical Mechanism to construct a two-dimensional model for gas-phase glyoxal chemistry in Los Angeles, assuming that the difference between the modeled and measured glyoxal concentration is available for aerosol uptake. Third, we examine the nighttime loss of glyoxal in the absence of its photochemical sources and sinks. Using these methods we constrain the glyoxal loss to aerosol to be 0-5 × 10-5 s-1 during clear days and (1 ± 0.3) × 10-5 s-1 at night. Between 07:00-15:00 local time, the diurnally averaged secondary organic aerosol mass increases from 3.2 μg m-3 to a maximum of 8.8 μg m -3. The constraints on the glyoxal budget from this analysis indicate that it contributes 0-0.2 μg m-3 or 0-4% of the secondary organic aerosol mass. Copyright 2011 by the American Geophysical Union

A Systematic Review Comparing the Acceptability, Validity and Concordance of Discrete Choice Experiments and Best–Worst Scaling for Eliciting Preferences in Healthcare

Objective: The aim of this study was to compare the acceptability, validity and concordance of discrete choice experiment (DCE) and best–worst scaling (BWS) stated preference approaches in health. Methods: A systematic search of EMBASE, Medline, AMED, PubMed, CINAHL, Cochrane Library and EconLit databases was undertaken in October to December 2016 without date restriction. Studies were included if they were published in English, presented empirical data related to the administration or findings of traditional format DCE and object-, profile- or multiprofile-case BWS, and were related to health. Study quality was assessed using the PREFS checklist. Results: Fourteen articles describing 12 studies were included, comparing DCE with profile-case BWS (9 studies), DCE and multiprofile-case BWS (1 study), and profile- and multiprofile-case BWS (2 studies). Although limited and inconsistent, the balance of evidence suggests that preferences derived from DCE and profile-case BWS may not be concordant, regardless of the decision context. Preferences estimated from DCE and multiprofile-case BWS may be concordant (single study). Profile- and multiprofile-case BWS appear more statistically efficient than DCE, but no evidence is available to suggest they have a greater response efficiency. Little evidence suggests superior validity for one format over another. Participant acceptability may favour DCE, which had a lower self-reported task difficulty and was preferred over profile-case BWS in a priority setting but not necessarily in other decision contexts. Conclusion: DCE and profile-case BWS may be of equal validity but give different preference estimates regardless of the health context; thus, they may be measuring different constructs. Therefore, choice between methods is likely to be based on normative considerations related to coherence with theoretical frameworks and on pragmatic considerations related to ease of data collection

Virtual rehabilitation for multiple sclerosis using a Kinect-based system: randomized controlled trial

©Jose-Antonio Lozano-Quilis, Hermenegildo Gil-Gómez, Jose-Antonio Gil-Gómez, Sergio Albiol-Pérez, Guillermo Palacios-Navarro, Habib M Fardoun, Abdulfattah S Mashat. Originally published in JMIR Serious Games (http://games.jmir.org), 12.11.2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Serious Games, is properly cited. The complete bibliographic information, a link to the original publication on http://games.jmir.org, as well as this copyright and license information must be included.Background: The methods used for the motor rehabilitation of patients with neurological disorders include a number of different rehabilitation exercises. For patients who have been diagnosed with multiple sclerosis (MS), the performance of motor rehabilitation exercises is essential. Nevertheless, this rehabilitation may be tedious, negatively influencing patients motivation and adherence to treatment. Objective: We present RemoviEM, a system based on Kinect that uses virtual reality (VR) and natural user interfaces (NUI) to offer patients with MS an intuitive and motivating way to perform several motor rehabilitation exercises. It offers therapists a new motor rehabilitation tool for the rehabilitation process, providing feedback on the patient s progress. Moreover, it is a low-cost system, a feature that can facilitate its integration in clinical rehabilitation centers. Methods: A randomized and controlled single blinded study was carried out to assess the influence of a Kinect-based virtual rehabilitation system on the balance rehabilitation of patients with MS. This study describes RemoviEM and evaluates its effectiveness compared to standard rehabilitation. To achieve this objective, a clinical trial was carried out. Eleven patients from a MS association participated in the clinical trial. The mean age was 44.82 (SD 10.44) and the mean time from diagnosis (years) was 9.77 (SD 10.40). Clinical effectiveness was evaluated using clinical balance scales. Results: Significant group-by-time interaction was detected in the scores of the Berg Balance Scale (P=.011) and the Anterior Reach Test in standing position (P=.011). Post-hoc analysis showed greater improvement in the experimental group for these variables than in the control group for these variables. The Suitability Evaluation Questionnaire (SEQ) showed good results in usability, acceptance, security, and safety for the evaluated system. Conclusions: The results obtained suggest that RemoviEM represents a motivational and effective alternative to traditional motor rehabilitation for MS patients. These results have encouraged us to improve the system with new exercises, which are currently being developed.This contribution was partially funded by the Generalitat Valenciana ("Ajudes per a la realitzacio de projectes d'I+D per a grups d'investigacion emergents", projecte GV/2012/069) and by the Fundacion Antonio Gargallo ("Ayudas financiadas por la Obra Social de Ibercaja de proyectos de investigacion 2013", proyecto 2013/B001).Lozano Quilis, JA.; Gil Gómez, H.; Gil-Gómez, J.; Albiol Pérez, S.; Palacios Navarro, G.; Fardoun, HM.; Mashat, AS. (2014). Virtual rehabilitation for multiple sclerosis using a Kinect-based system: randomized controlled trial. JMIR Serious Games. 2(2). https://doi.org/10.2196/games.2933Se1222Adamovich, S. V., Fluet, G. G., Tunik, E., & Merians, A. S. (2009). Sensorimotor training in virtual reality: A review. Neurorehabilitation, 25(1), 29-44. doi:10.3233/nre-2009-0497Lange, B., Flynn, S., Proffitt, R., Chang, C.-Y., & «Skip» Rizzo, A. (2010). Development of an Interactive Game-Based Rehabilitation Tool for Dynamic Balance Training. Topics in Stroke Rehabilitation, 17(5), 345-352. doi:10.1310/tsr1705-345Lozano, J. A., Montesa, J., Juan, M. C., Alcañiz, M., Rey, B., Gil, J., … Morganti, F. (2005). VR-Mirror: A Virtual Reality System for Mental Practice in Post-Stroke Rehabilitation. Lecture Notes in Computer Science, 241-251. doi:10.1007/11536482_23Lange, B. S., Requejo, P., Flynn, S. M., Rizzo, A. A., Valero-Cuevas, F. J., Baker, L., & Winstein, C. (2010). The Potential of Virtual Reality and Gaming to Assist Successful Aging with Disability. Physical Medicine and Rehabilitation Clinics of North America, 21(2), 339-356. doi:10.1016/j.pmr.2009.12.007Wuang, Y.-P., Chiang, C.-S., Su, C.-Y., & Wang, C.-C. (2011). Effectiveness of virtual reality using Wii gaming technology in children with Down syndrome. Research in Developmental Disabilities, 32(1), 312-321. doi:10.1016/j.ridd.2010.10.002Chang, Y.-J., Chen, S.-F., & Huang, J.-D. (2011). A Kinect-based system for physical rehabilitation: A pilot study for young adults with motor disabilities. Research in Developmental Disabilities, 32(6), 2566-2570. doi:10.1016/j.ridd.2011.07.002Da GamaAChavezTFigueiredoLTeichriebVPoster: improving motor rehabilitation process through a natural interaction based system using kinect sensor, IEEE Symposium on 3D User Interfaces 2012: 145-1462012IEEE Symposium on 3D User InterfacesMar 4-5Costa Mesa, CABaram, Y., & Miller, A. (2006). Virtual reality cues for improvement of gait in patients with multiple sclerosis. Neurology, 66(2), 178-181. doi:10.1212/01.wnl.0000194255.82542.6bFulk, G. D. (2005). Locomotor Training and Virtual Reality-based Balance Training for an Individual with Multiple Sclerosis. Journal of Neurologic Physical Therapy, 29(1), 34-42. doi:10.1097/01.npt.0000282260.59078.e4Lozano-QuilisJAAlbiol-PerezSGil-GomezHPalaciosGFardoumHMGil-GomezJAMashatASVirtual reality system for multiple sclerosis rehabilitation using KINECT2013International Conference on Pervasive Computing Technologies for Healthcare (PervasiveHealth)May 5-8Venice, Italy366369Van Hedel, H. J., Wirz, M., & Dietz, V. (2005). Assessing walking ability in subjects with spinal cord injury: Validity and reliability of 3 walking tests. Archives of Physical Medicine and Rehabilitation, 86(2), 190-196. doi:10.1016/j.apmr.2004.02.010Podsiadlo, D., & Richardson, S. (1991). The Timed «Up & Go»: A Test of Basic Functional Mobility for Frail Elderly Persons. Journal of the American Geriatrics Society, 39(2), 142-148. doi:10.1111/j.1532-5415.1991.tb01616.xSteffen, T. M., Hacker, T. A., & Mollinger, L. (2002). Age- and Gender-Related Test Performance in Community-Dwelling Elderly People: Six-Minute Walk Test, Berg Balance Scale, Timed Up & Go Test, and Gait Speeds. Physical Therapy, 82(2), 128-137. doi:10.1093/ptj/82.2.128Gil-GomezJASEQ: Suitability Evaluation Questionnaire for Virtual Rehabilitation systems2013International Conference on Pervasive Computing Technologies for Healthcare (PervasiveHealth)2013Venice, Italy33533

An intervention to improve outcomes of falls in dementia: the DIFRID mixed-methods feasibility study:A mixed methods study to develop and assess the feasibility of the DIFRID intervention

Background : Fall-related injuries are a significant cause of morbidity and mortality in people with dementia (PWD). There is presently little evidence to guide the management of such injuries, and yet there are potentially substantial benefits to be gained if the outcome of these injuries could be improved. This study aimed to design an appropriate new healthcare intervention for PWD following a fall and to assess the feasibility of its delivery in the UK National Health Service. Objective (s): To determine whether it is possible to design an intervention to improve outcomes of falls in dementia; to investigate the feasibility and acceptability of the DIFRID intervention; to investigate the feasibility of a future randomised controlled trial (RCT) and data collection tools needed to evaluate the effectiveness and efficiency of the DIFRID intervention. Design : Mixed-methods feasibility study. Methods : A systematic review (using Cochrane methodology) and realist review (using RAMESES methodology) explored the existing evidence base and developed programme theories. Searches were carried out in Nov 2015 (updated Jan 2018) for effectiveness studies and August 2016 for economic studies. A prospective observational study identified service use via participant diary completion. Qualitative methods (semi-structured interviews, focus groups, and observation) were used to explore: current practice; stakeholder perspectives of the health and social care needs of PWD following a fall; ideas for intervention; and barriers and facilitators to change. Each of these datasets informed intervention development, via Delphi consensus methods. Finally, a single-arm feasibility study with embedded process evaluation was conducted. Setting : Community. Participants : PWD presenting with falls needing healthcare attention in each setting at 3 sites and their carers. Professionals delivering the intervention, responsible for training and supervision and members of the intervention team. Professionals responsible for approaching and recruiting participants. Interventions: A complex multidisciplinary therapy intervention. Physiotherapists, occupational therapists, and support workers delivered up to 22 sessions of tailored activities in the PWD’s home or local area over a period of 12 weeks. Main outcome measures: Assessment of feasibility of study procedures; assessment of the acceptability, feasibility and fidelity of intervention components; assessment of suitability and acceptability of outcome measures for PWD and carers (number of falls; quality of life; fear of falling; activities of daily living; goal setting; health utilisation; carer burden). Results : A multidisciplinary intervention delivered in PWDs’ own homes was designed based on qualitative work, realist review and recommendations of the consensus panel. The intervention was delivered to 11 PWD. The study suggested that the intervention is both feasible and acceptable to stakeholders. A number of modifications was recommended to address some of the issues arising during feasibility testing. Measurement of outcome measures was successful. Limitations : Recruitment to the feasibility study was lower than expected and therefore the intervention needs to be tested with a larger number of PWD. Conclusions : The study has highlighted the feasibility of delivering a creative, tailored, individual approach to intervention for PWD following a fall. Although the intervention required greater investment of time than usual practice, many staff valued the opportunity to work more closely with PWD and carers. Future work : We conclude that further research is now needed to refine this intervention in the context of a pilot randomised controlled trial

Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study

Background A phase I study found remarkable activity and manageable toxicity for doxorubicin (bolus) plus lurbinectedin (1-h intravenous [i.v.] infusion) on Day 1 every three weeks (q3wk) as second-line therapy in relapsed small cell lung cancer (SCLC). An expansion cohort further evaluated this combination. Patients and methods Twenty-eight patients with relapsed SCLC after no more than one line of cytotoxic-containing chemotherapy were treated: 18 (64%) with sensitive disease (chemotherapy-free interval [CTFI] ≥90 days) and ten (36%) with resistant disease (CTFI <90 days; including six with refractory disease [CTFI ≤30 days]). Results Ten patients showed confirmed response (overall response rate [ORR] = 36%); median progression-free survival (PFS) = 3.3 months; median overall survival (OS) = 7.9 months. ORR was 50% in sensitive disease (median PFS = 5.7 months; median OS = 11.5 months) and 10% in resistant disease (median PFS = 1.3 months; median OS = 4.6 months). The main toxicity was transient and reversible myelosuppression. Treatment-related non-hematological events (fatigue, nausea, decreased appetite, vomiting, alopecia) were mostly mild or moderate. Conclusion Doxorubicin 40 mg/m(2) and lurbinectedin 2.0 mg/m(2) on Day 1 q3wk has shown noteworthy activity in relapsed SCLC and a manageable safety profile. The combination is being evaluated as second-line therapy for SCLC in an ongoing, randomized phase III trial. Clinical trial registration www.ClinicalTrials.gov code: NCT01970540. Date of registration: 22 October, 2013

Two-loop Corrections to the B to pi Form Factor from QCD Sum Rules on the Light-Cone and |V(ub)|

We calculate the leading-twist O(alphas^2 beta0) corrections to the B to pi transition form factor f+(0) in light-cone sum rules. We find that, as expected, there is a cancellation between the O(alphas^2 beta0) corrections to fB f+(0) and the large corresponding corrections to fB, calculated in QCD sum rules. This suggests the insensitivity of the form factors calculated in the light-cone sum rules approach to this source of radiative corrections. We further obtain an improved determination of the CKM matrix element |V(ub)|, using latest results from BaBar and Belle for f+(0)|V(ub)|.Comment: 18 pages, 3 figure

Theoretical and Phenomenological Constraints on Form Factors for Radiative and Semi-Leptonic B-Meson Decays

We study transition form factors for radiative and rare semi-leptonic B-meson decays into light pseudoscalar or vector mesons, combining theoretical constraints and phenomenological information from Lattice QCD, light-cone sum rules, and dispersive bounds. We pay particular attention to form factor parameterisations which are based on the so-called series expansion, and study the related systematic uncertainties on a quantitative level. In this context, we also provide the NLO corrections to the correlation function between two flavour-changing tensor currents, which enters the unitarity constraints for the coefficients in the series expansion.Comment: 52 pages; v2: normalization error in (29ff.) corrected, conclusion about relevance of unitarity bounds modified; form factor fits unaffected; references added; v3: discussion on truncation of series expansion added, matches version to be published in JHEP; v4: corrected typos in Tables 5 and