A numerical and experimental investigation of the effect of side walls on hydrodynamic model testing in a wave flume

The side wall effect was normally tackled by potential flow based numerical methods. It is well known that, due to the existence of the resonance frequency in the wave tank, the numerical methods over-predict the hydrodynamic forces when comparing with model experiments. Furthermore, in most of the previous studies on the effects of the side walls, the model was located at the centre of the tank, the disturbances on both sides of the model are symmetric, and the resonances of some of the responses such as wave surface elevation and motions may not be excited at the tank natural frequencies. In the present study, a Rankine source panel method is used to tackle the effects of the side walls and artificial damping is introduced in the free surface boundary condition to account for the viscous damping effect. Model experiments are carried out for a lifeboat model located at various positions in a wave flume. Numerical results of the wave forces, free surface elevations and motions of the model are compared with the model test measurements, and good agreement is found. It is shown that the inclusion of the artificial damping in the free surface boundary condition is effective, in particular for the model at off-centre position of the tank

Third-Line Nivolumab Monotherapy in Recurrent Small Cell Lung Cancer : CheckMate 032

Introduction: For patients with recurrent SCLC, topotecan remains the only approved second-line treatment, and the outcomes are poor. CheckMate 032 is a phase 1/2, multicenter, open-label study of nivolumab or nivolumab plus ipilimumab in SCLC or other advanced/metastatic solid tumors previously treated with one or more platinum-based chemotherapies. We report results of third- or later-line nivolumab monotherapy treatment in SCLC. Methods: In this analysis, patients with limited-stage or extensive-stage SCLC and disease progression after two or more chemotherapy regimens received nivolumab monotherapy, 3 mg/kg every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival, overall survival, and safety. Results: Between December 4, 2013, and November 30, 2016, 109 patients began receiving third- or later-line nivolumab monotherapy. At a median follow-up of 28.3 months (from first dose to database lock), the objective response rate was 11.9% (95% confidence interval: 6.5\u201319.5) with a median duration of response of 17.9 months (range 3.0\u201342.1). At 6 months, 17.2% of patients were progression-free. The 12-month and 18-month overall survival rates were 28.3% and 20.0%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 11.9% of patients. Three patients (2.8%) discontinued because of treatment-related adverse events. Conclusions: Nivolumab monotherapy provided durable responses and was well tolerated as a third- or later-line treatment for recurrent SCLC. These results suggest that nivolumab monotherapy is an effective third- or later-line treatment for this patient population

Nebuliser therapy in the intensive care unit

The relationship between identity, lived experience, sexual practices and the language through which these are conveyed has been widely debated in sexuality literature. For example, ‘coming out’ has famously been conceptualised as a ‘speech act’ (Sedgwick 1990) and as a collective narrative (Plummer 1995), while a growing concern for individuals’ diverse identifications in relations to their sexual and gender practices has produced interesting research focusing on linguistic practices among LGBT-identified individuals (Leap 1995; Kulick 2000; Cameron and Kulick 2006; Farqhar 2000). While an explicit focus on language remains marginal to literature on sexualities (Kulick 2000), issue of language use and translation are seldom explicitly addressed in the growing literature on intersectionality. Yet intersectional perspectives ‘reject the separability of analytical and identity categories’ (McCall 2005:1771), and therefore have an implicit stake in the ‘vernacular’ language of the researched, in the ‘scientific’ language of the researcher and in the relationship of continuity between the two. Drawing on literature within gay and lesbian/queer studies and cross-cultural studies, this chapter revisits debates on sexuality, language and intersectionality. I argue for the importance of giving careful consideration to the language we choose to use as researchers to collectively define the people whose experiences we try to capture. I also propose that language itself can be investigated as a productive way to foreground how individual and collective identifications are discursively constructed, and to unpack the diversity of lived experience. I address intersectional complexity as a methodological issue, where methodology is understood not only as the methods and practicalities of doing research, but more broadly as ‘a coherent set of ideas about the philosophy, methods and data that underlie the research process and the production of knowledge’ (McCall 2005:1774). My points are illustrated with examples drawn from my ethnographic study on ‘lesbian’ identity in urban Russia, interspersed with insights from existing literature. In particular, I aim to show that an explicit focus on language can be a productive way to explore the intersections between the global, the national and the local in cross-cultural research on sexuality, while also addressing issues of positionality and accountability to the communities researched

Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model

BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. METHODOLOGY/PRINCIPLE FINDINGS: EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). CONCLUSIONS/SIGNIFICANCE: Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells for effective treatment of human patients with recurrent glioblastoma

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

Playing the victim? Human trafficking, African youth, and geographies of structural inequality

This article explores the role of agency in determining who is and is not considered to be a legitimate victim of human trafficking. It draws on critical human trafficking scholarship and research on the life chances of West African youth. This is complemented by qualitative data from youth embroiled in football-related human trafficking. The insights from these analyses are brought into conversation with theoretical work on the geographies of commodities. This results in the concept of ‘unveiling the football trafficking fetish’, which is used to theorise how and why the agency of mobile youthful African male bodies undermines their claims of being trafficked human beings. The findings that emerge are significant in two ways. First, they generate theoretical insights on the coexistence of agency and exploitation in young lives, and how young people’s aspirations and agency can be (mis)read and work against them. Second, they provide a unique illustration of how human trafficking is a product of capitalism yet can be presented as a form of behaviour that lies outside of capitalist social relations. To centre these social relations and foster new forms of critical dialogue within and beyond population geography, the article concludes by recommending we consider the implications of conceptualising people as susceptible to rather than vulnerable to human trafficking

The internal brakes on violent escalation:a typology

Most groups do less violence than they are capable of. Yet while there is now an extensive literature on the escalation of or radicalisation towards violence, particularly by ‘extremist’ groups or actors, and while processes of de-escalation or de-radicalisation have also received significant attention, processes of non- or limited escalation have largely gone below the analytical radar. This article contributes to current efforts to address this limitation in our understanding of the dynamics of political aggression by developing a descriptive typology of the ‘internal brakes’ on violent escalation: the mechanisms through which members of the groups themselves contribute to establish and maintain limits upon their own violence. We identify five underlying logics on which the internal brakes operate: strategic, moral, ego maintenance, outgroup definition, and organisational. The typology is developed and tested using three very different case studies: the transnational and UK jihadi scene from 2005 to 2016; the British extreme right during the 1990s, and the animal liberation movement in the UK from the mid-1970s until the early 2000s

Measuring health inequalities in Albania: a focus on the distribution of general practitioners

BACKGROUND: The health workforce has a dynamically changing nature and the regular documentation of the distribution of health professionals is a persistent policy concern. The aim of the present study was to examine available human medical resources in primary care and identify possible inequalities regarding the distribution of general practitioners in Albania between 2000 and 2004. METHODS: With census data, we investigated the degree of inequality by calculating relative inequality indices. We plotted the Lorenz curves and calculated the Gini, Atkinson and Robin Hood indices and decile ratios, both before and after adjusting for mortality and consultation rates. RESULTS: The Gini index for the distribution of general practitioners in 2000 was 0.154. After adjusting for mortality it was 0.126, while after adjusting for consultation rates it was 0.288. The Robin Hood index for 2000 was 11.2%, which corresponds to 173 general practitioners who should be relocated in order to achieve equality. The corresponding figure after adjusting for mortality was 9.2% (142 general practitioners), while after adjusting for consultation rates the number was 20.6% (315). These figures changed to 6.3% (100), 6.3% (115) and 19.8% (315) in 2004. CONCLUSION: There was a declining trend in the inequality of distribution of general practitioners in Albania between 2000 and 2004. The trend in inequality was apparent irrespective of the relative inequality indicator used. The level of inequality varied depending on the adjustment method used. Reallocation strategies for general practitioners in Albania could be the key in alleviating the inequalities in primary care workforce distribution