Repeated sprints: an independent not dependent variable

The ability to repeatedly perform sprints has traditionally been viewed as a key performance measure in team sports, and the relationship between repeated-sprint ability (RSA) and performance has been explored extensively. However, when reviewing the repeated-sprint profile of team-sports match play it appears that the occurrence of repeated-sprint bouts is sparse, indicating that RSA is not as important to performance as commonly believed. Repeated sprints are, however, a potent and time-efficient training strategy, effective in developing acceleration, speed, explosive leg power, aerobic power, and high-intensity-running performance—all of which are crucial to team-sport performance. As such, we propose that repeated-sprint exercise in team sports should be viewed as an independent variable (eg, a means of developing fitness) as opposed to a dependent variable (eg, a means of assessing fitness/performance)

The Holographic Dual of 2+1 Dimensional QFTs with N=1 SUSY and Massive Fundamental Flavours

The Maldacena Nastase solution is generalised to include massive fundamental matter through the addition of a flavour profile. This gives a holographic dual to N=1 SYM-CS with massive fundamental matter with a singularity free IR. We study this solution in some detail confirming confinement and asymptotic freedom. A recently proposed solution generating technique is then applied which results in a new type-IIA supergravity solution. In a certain limit the geometry of this solution is asymptotically AdS_4X Y, where Y is the metric at the base of the Bryant-Salamon G_2 cone, which has topology S^3XS^3.Comment: 31 pages plus appendices, 6 figures. v3: Typos corrected, version to appear in JHE

Understanding antimicrobial resistance through the lens of antibiotic vulnerabilities in primary health care in rural Malawi

The diminishing effectiveness of antimicrobials raises serious concerns for human health. While policy makers grapple to reduce the overuse of antimicrobial medicines to stem the rise of antimicrobial resistance, insufficient attention has been paid to how this applies to low-resource contexts. We provide an in-depth portrayal of antimicrobial prescribing at primary health care level in rural Chikwawa District, Malawi. Ethnographic fieldwork took place over 18 months (2018–2020). We surveyed 22 health facilities in the district, observed 1348 health worker-patient consultations, and carried out 49 in-depth interviews with staff and patients. Care was centred around provision of an antimicrobial. Amid chronic lack of essential medicines and other resources, clinic interactions were tightly scripted, providing patients little time to question or negotiate their treatment. We develop the concept of ‘antibiotic vulnerabilities’ to reveal multiple ways in which provision of antimicrobials in rural Malawi impacts care in conditions of extreme scarcity. Antibiotics are central and essential to primary care. As targets for optimal antimicrobial prescribing take a more central role in global policy, close attention is required of the ramifications for the delivery of care to ensure that efforts to stem resistance do not undermine the goal of improved health for all

Holographic flows in non-Abelian T-dual geometries

We use non-Abelian T-duality to construct new N=1 solutions of type IIA supergravity (and their M-theory lifts) that interpolate between AdS_5 geometries. We initiate a study of the holographic interpretation of these backgrounds as RG flows between conformal fixed points. Along the way we give an elegant formulation of non-Abelian T-duality when acting on a wide class of backgrounds, including those corresponding to such flows, in terms of their SU(2) structure

Antibiotic Arrivals in Africa: A Case Study of Yaws and Syphilis in Malawi, Zimbabwe and Uganda

The mass production of antibiotics in the 1940s enabled their travel beyond Europe and America, but to date the significance of the ways in which these medicines co-constituted colonial regimes at the time has not been systematically described. Through a case study of yaws and syphilis, this research article traces arrivals of antibiotics in three countries of Eastern Africa—Malawi, Zimbabwe, and Uganda. We draw attention to the emergent roles of antibiotics at the intersection of colonial governance and humanitarianism in these different settings. Through this analysis of archival and ethnographic materials, we explore how antibiotics became ‘infrastructural’ in material, affective, and political ways. Achieving a better understanding of the entanglement of antibiotics with human systems and lives is crucial to address the pressing issue of antimicrobial resistance (AMR). With this article we join in the global multidisciplinary efforts to tackle AMR, pointing out the often-overlooked role of colonial history in the circulation of antibiotic drugs, and opening a line of research that will provide valuable insights for the development of effective measures to prevent and reduce the spread of antibiotic resistance

Antibiotics and the Biopolitics of Sex Work in Zimbabwe.

The advent of antibiotics transformed the global public health landscape, dramatically improving health outcomes. Drawing on historical and ethnographic research on sex work in Zimbabwe, we examine the role of antibiotics in the management of sexually transmitted infections among sex workers, from punitive colonial approaches to "empowerment"-based discourses. We illustrate how programs for sex workers, while valued by these women, are narrow, exclusionary, and enact a pharmaceuticalized form of governance that hangs on the efficacy of antibiotics. With antibiotics' efficacy under threat, we consider how latent colonial logics are in danger of being reactivated to control both infections and women

A Complex Systems Science Perspective for Whole Systems of Complementary and Alternative Medicine Research

Whole systems complementary and alternative medicine (WS-CAM) approaches share a basic worldview that embraces interconnectedness; emergent, non-linear outcomes to treatment that include both local and global changes in the human condition; a contextual view of human beings that are inseparable from and responsive to their environments; and interventions that are complex, synergistic, and interdependent. These fundamental beliefs and principles run counter to the assumptions of reductionism and conventional biomedical research methods that presuppose unidimensional simple causes and thus dismantle and individually test various interventions that comprise only single aspects of the WS-CAM system. This paper will demonstrate the superior fit and practical advantages of using complex adaptive systems (CAS) and related modeling approaches to develop the scientific basis for WS-CAM. Furthermore, the details of these CAS models will be used to provide working hypotheses to explain clinical phenomena such as (a) persistence of changes for weeks to months between treatments and/or after cessation of treatment, (b) nonlocal and whole systems changes resulting from therapy, (c) Hering\u27s law, and (d) healing crises. Finally, complex systems science will be used to offer an alternative perspective on cause, beyond the simple reductionism of mainstream mechanistic ontology and more parsimonious than the historical vitalism of WS-CAM. Rather, complex systems science provides a scientifically rigorous, yet essentially holistic ontological perspective with which to conceptualize and empirically explore the development of disease and illness experiences, as well as experiences of healing and wellness

Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study

Background: Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate comprised of trastuzumab covalently bound to a linker drug containing duocarmycin. Preclinical studies showed promising antitumour activity in various models. In this first-in-human study, we assessed the safety and activity of trastuzumab duocarmazine in patients with advanced solid tumours. Methods: We did a phase 1 dose-escalation and dose-expansion study. The dose-escalation cohort comprised patients aged 18 years or older enrolled from three academic hospitals in Belgium, the Netherlands, and the UK with locally advanced or metastatic solid tumours with variable HER2 status who were refractory to standard cancer treatment. A separate cohort of patients were enrolled to the dose-expansion phase from 15 hospitals in Belgium, the Netherlands, Spain, and the UK. Dose-expansion cohorts included patients aged 18 years or older with breast, gastric, urothelial, or endometrial cancer with at least HER2 immunohistochemistry 1+ expression and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST). Trastuzumab duocarmazine was administered intravenously on day 1 of each 3-week cycle. In the dose-escalation phase, trastuzumab duocarmazine was given at doses of 0.3 mg/kg to 2.4 mg/kg (3 + 3 design) until disease progression or unacceptable toxicity. The primary endpoint of the dose-escalation phase was to assess safety and ascertain the recommended phase 2 dose, which would be the dose used in the dose-expansion phase. The primary endpoint of the dose-expansion phase was the proportion of patients achieving an objective response (complete response or partial response), as assessed by the investigator using RECIST version 1.1. This ongoing study is registered with ClinicalTrials.gov, number NCT02277717, and is fully recruited. Findings: Between Oct 30, 2014, and April 2, 2018, 39 patients were enrolled and treated in the dose-escalation phase and 146 patients were enrolled and treated in the dose-expansion phase. One dose-limiting toxic effect (death from pneumonitis) occurred at the highest administered dose (2.4 mg/kg) in the dose-escalation phase. One further death occurred in the dose-escalation phase (1.5 mg/kg cohort) due to disease progression, which was attributed to general physical health decline. Grade 3-4 treatment-related adverse events reported more than once in the dose-escalation phase were keratitis (n=3) and fatigue (n=2). Based on all available data, the recommended phase 2 dose was set at 1.2 mg/kg. In the dose-expansion phase, treatment-related serious adverse events were reported in 16 (11%) of 146 patients, most commonly infusion-related reactions (two [1%]) and dyspnoea (two [1%]). The most common treatment-related adverse events (grades 1-4) were fatigue (48 [33%] of 146 patients), conjunctivitis (45 [31%]), and dry eye (45 [31%]). Most patients (104 [71%] of 146) had at least one ocular adverse event, with grade 3 events reported in ten (7%) of 146 patients. No patients died from treatment-related adverse events and four patients died due to disease progression, which were attributed to hepatic failure (n=1), upper gastrointestinal haemorrhage (n=1), neurological decompensation (n=1), and renal failure (n=1). In the breast cancer dose-expansion cohorts, 16 (33%, 95% CI 20.4-48.4) of 48 assessable patients with HER2-positive breast cancer achieved an objective response (all partial responses) according to RECIST. Nine (28%, 95% CI 13.8-46.8) of 32 patients with HER2-low, hormone receptor-positive breast cancer and six (40%, 16.3-67.6) of 15 patients with HER2-low, hormone receptor-negative breast cancer achieved an objective response (all partial responses). Partial responses were also observed in one (6%, 95% CI 0.2-30.2) of 16 patients with gastric cancer, four (25%, 7.3-52.4) of 16 patients with urothelial cancer, and five (39%, 13.9-68.4) of 13 patients with endometrial cancer. Interpretation: Trastuzumab duocarmazine shows notable clinical activity in heavily pretreated patients with HER2-expressing metastatic cancer, including HER2-positive trastuzumab emtansine-resistant and HER2-low breast cancer, with a manageable safety profile. Further investigation of trastuzumab duocarmazine for HER2-positive breast cancer is ongoing and trials for HER2-low breast cancer and other HER2-expressing cancers are in preparation. Copyright (C) 2019 Elsevier Ltd. All rights reserved

Type IIB supergravity solutions with AdS5 from Abelian and non-Abelian T dualities

We present a large class of new backgrounds that are solutions of type IIB supergravity with a warped AdS${}_5$ factor, non-trivial axion-dilaton, $B$-field and three-form Ramond-Ramond flux but yet have no five-form flux. We obtain these solutions and many of their variations by judiciously applying non-Abelian and Abelian T-dualities, as well as coordinate shifts to AdS${}_5\times X_5$ IIB supergravity solutions with $X_5=S^5, T^{1,1}, Y^{p,q}$. We address a number of issues pertaining to charge quantization in the context of non-Abelian T-duality. We comment on some properties of the expected dual super conformal field theories by studying their CFT central charge holographically. We also use the structure of the supergravity Page charges, central charges and some probe branes to infer aspects of the dual super conformal field theories.Comment: 71 pages, one table. v2: References added, some normalizations corrected, results unchange