Representing Strategic International Human Resource Management: Is the Map the Territory?

This paper is focused on the emergent field of strategic international human resource management (SIHRM). We suggest that SIHRM is becoming an integrated intellectual map in terms of: (1) the typologies created; (2) the language used; and (3) its pedagogy. Does the way in which we articulate SIHRM assist theory development or enact intellectual imperialism? Or both? It is argued that, by exploring the implications of SIHRM for theory, research, practice and teaching, we may raise awareness of current deficiencies and unanswered questions. Do we need to set a new course, or at least make explicit our navigational assumptions

Is primary angioplasty cost effective in the UK? Results of a comprehensive decision analysis

Objective: To assess the cost effectiveness of primary angioplasty, compared with medical management with thrombolytic drugs, to achieve reperfusion after acute myocardial infarction ( AMI) from the perspective of the UK NHS. Design: Bayesian evidence synthesis and decision analytic model. Methods: A systematic review was conducted and Bayesian statistical methods used to synthesise evidence from 22 randomised control trials. Resource utilisation was based on UK registry data, published literature and national databases, with unit costs taken from routine NHS sources and published literature. Main outcome measure: Costs from a health service perspective and outcomes measured as quality-adjusted life years (QALYs). Results: For the base case, the incremental cost-effectiveness ratio of primary angioplasty was pound 9241 for each additional QALY, with a probability of being cost effective of 0.90 for a cost-effectiveness threshold of pound 20 000. Results were sensitive to variations in the additional time required to initiate treatment with primary angioplasty. Conclusions: Primary angioplasty is cost effective for the treatment of AMI on the basis of threshold cost-effectiveness values used in the NHS and subject to a delay of up to about 80 minutes. These findings are mainly explained by the superior mortality benefit and the prevention of non-fatal outcomes associated with primary angioplasty for delays of up to this length

Assessing the effectiveness of primary angioplasty compared with thrombolysis and its relationship to time delay: a Bayesian evidence synthesis

Background: Meta-analyses of trials have shown greater benefits from angioplasty than thrombolysis after an acute myocardial infarction, but the time delay in initiating angioplasty needs to be considered. Objective: To extend earlier meta-analyses by considering 1- and 6-month outcome data for both forms of reperfusion. To use Bayesian statistical methods to quantify the uncertainty associated with the estimated relationships. Methods: A systematic review and meta-analysis published in 2003 was updated. Data on key clinical outcomes and the difference between time-to-balloon and time-to-needle were independently extracted by two researchers. Bayesian statistical methods were used to synthesise evidence despite differences between reported follow-up times and outcomes. Outcomes are presented as absolute probabilities of specific events and odds ratios (ORs; with 95% credible intervals (Crl)) as a function of the additional time delay associated with angioplasty. \ Results: 22 studies were included in the meta-analysis, with 3760 and 3758 patients randomised to primary angioplasty and thrombolysis, respectively. The mean ( SE) angioplasty-related time delay ( over and above time to thrombolysis) was 54.3 (2.2) minutes. For this delay, mean event probabilities were lower for primary angioplasty for all outcomes. Mortality within 1 month was 4.5% after angioplasty and 6.4% after thrombolysis ( OR = 0.68 ( 95% Crl 0.46 to 1.01)). For non-fatal reinfarction, OR = 0.32 ( 95% Crl 0.20 to 0.51); for non-fatal stroke OR = 0.24 ( 95% Crl 0.11 to 0.50). For all outcomes, the benefit of angioplasty decreased with longer delay from initiation. Conclusions: The benefit of primary angioplasty, over thrombolysis, depends on the former's additional time delay. For delays of 30-90 minutes, angioplasty is superior for 1- month fatal and non-fatal outcomes. For delays of around 90 minutes thrombolysis may be the preferred option as assessed by 6-month mortality; there is considerable uncertainty for longer time delays

Think global, act local: from naive comparison to critical participation in the teaching of strategic international human resource management

In this paper, we examine the implications of ethnocentrism and paternalism in teaching approaches for the field of strategic international human resource management (SIHRM), as an example of management studies. We argue that the teaching of SIHRM has been approached in a colonizing fashion, joining and extending the territories of human resource management and organizational strategy through the definition and teaching of a new language and conceptual vocabulary. We explore philosophical approaches and processes involved in teaching SIHRM, and consider implications of pedagogical developments in this field of management education.<br /

National counter-terrorism (C-T) policies and challenges to human rights and civil liberties: Case study of United Kingdom

In the UK the rise post-2005 in “home-grown” terrorism, relying to a significant extent on strikes on soft targets by “self-starters,” means that the search for effective preventive measures remains a continuing concern. Below a number of the preventive counter-terror measures adopted post-9/11, and incrementally strengthened in response to the current threat, are found to fall into three categories and represent interventions at the stages in the path toward attacks. This chapter focuses on selected examples of these preventive measures. In terms of three key stages, firstly, there is the attempt to prevent radicalization, under the “Prevent” strategy. A second strategy relies on taking certain measures to control the activities of those considered likely – on the balance of probabilities – to engage in terrorist-related activity. A third preventive strategy relies on the special terrorism offences under the Terrorism Acts 2000 and 2006, as amended, intended to allow for intervention at a very early stage in terrorist plots and in preparing or instigating terrorist acts (“precursor” offences)

EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor

ACKNOWLEDGEMENTS We thank J. M. Valverde (IRB) as well as the NMR facilities of the University of Barcelona (CCiT UB) and the Instituto de Química Física Rocasolano (IQFR, CSIC) for their assistance in, respectively, protein production and NMR. This work was supported by IRB, ICREA (X.S.), Obra Social “la Caixa” (Fellowship to E.D.M. and CancerTec grants to X.S.) MICINN (CTQ2009-08850 to X.S.), MINECO (BIO2012-31043 to X.S.; CTQ2014-56361-P to A.R), Marató de TV3 (102030 to X.S. and 102031 to E.E.P) the COFUND programme of the European Commission (C.T.W.P., A. R. and X.S.), the European Research Council (CONCERT, contract number 648201, to X.S.), the Ramón y Cajal program of MICINN (RYC-2011-07873 to C.W.B.) the Serra Hunter Programme (E.E.P.) and AGAUR (SGR-2014-56RR14 to E.E.P). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain)Peer reviewedPostprin

A CD64/FcγRI-mediated mechanism hijacks PD-1 from PD-L1/2 interaction and enhances anti-PD-1 functional recovery of exhausted T cells.

Therapeutic monoclonal antibodies (mAb) targeting the immune checkpoint inhibitor programmed cell death protein 1 (PD-1) have achieved considerable clinical success in anti-cancer therapy through relieving T cell exhaustion. Blockade of PD-1 interaction with its ligands PD-L1 and PD-L2 is an important determinant in promoting the functional recovery of exhausted T cells. Here, we show that anti-PD-1 mAbs act through an alternative mechanism leading to the downregulation of PD-1 surface expression on memory CD4 &lt;sup&gt;+&lt;/sup&gt; and CD8 &lt;sup&gt;+&lt;/sup&gt; T cells. PD-1 receptor downregulation is a distinct process from receptor endocytosis and occurs in a CD14 &lt;sup&gt;+&lt;/sup&gt; monocyte dependent manner with the CD64/Fcγ receptor I acting as the primary factor for this T cell extrinsic process. Importantly, downregulation of surface PD-1 strongly enhances antigen-specific functional recovery of exhausted PD-1 &lt;sup&gt;+&lt;/sup&gt; CD8 &lt;sup&gt;+&lt;/sup&gt; T cells. Our study demonstrates a novel mechanism for reducing cell surface levels of PD-1 and limiting the inhibitory targeting by PD-L1/2 and thereby enhancing the efficacy of anti-PD-1 Ab in restoring T cell functionality

In Situ Characterization of Follicular Helper CD4 T Cells Using Multiplexed Imaging.

Follicular helper CD4 T (Tfh) cells play an essential role in the formation of germinal centers (GCs), where mature B cells proliferate, differentiate, and provide long-term protective humoral responses. Despite the extensive phenotypic characterization and identification of human Tfh cell subsets, their spatial positioning at tissue level is not well understood. Here, we describe a quantitative multiplexed immunofluorescence approach allowing for the comprehensive in situ characterization of Tfh cells in human tonsils and lymph nodes (LNs) from individuals with angioimmunoblastic T-cell lymphoma (AITL). We have developed eight multiplexed panels comprising a spectrum of Tfh cell markers, like PD-1, CXCR5, and ICOS, along with transcription factors (Bcl6, Tbet, GATA3), to assess their expression, frequencies, spatial distribution and co-localization in a quantitative manner. Combined analysis of relevant markers revealed the presence of several Tfh cell subsets at tissue level based on the differential expression of surface receptors, nuclear factors as well as their distinct localization within the follicular areas. Interestingly, we found a considerable amount of tonsillar Tfh cells expressing high levels of the Th2 regulator GATA3. The co-expression of GATA3, CXCR5, and BCL6, points to an important role of GATA3 for the generation of effector human Tfh cells. Furthermore, our data revealed significantly different Tfh cell profile signatures between health and disease. Therefore, our imaging platform generates meaningful information for the in situ characterization of human Tfh cells and could provide the base for future studies aiming to a comprehensive understanding of Tfh cell tissue heterogeneity

Sociomateriality in medical practice and learning: Attuning to what matters

CONTEXT In current debates about professional practice, learning and education, increasing emphasis is being placed on understanding learning as ongoing participation rather than as acquiring knowledge and skills. Close attention is paid to the sociocultural context as well as to cognition. While this general sociocultural view is important and useful, issues have emerged in studies of practice-based learning that point to certain oversights. METHOD Three issues are described here: (1) the general lack of attention to the importance of materiality &ndash; objects, technologies, nature etc &ndash; in questions of learning; (2) the human-centric view of challenges and complexities in practice that fail to note the transformational entanglements among social and material forces; and (3) the conflicts between ideals of evidence-based standardized models and the sociomaterial contingencies of clinical practice.&nbsp; &nbsp; DISCUSSION It is argued here that a sociomaterial approach to learning and practice offers important insights for medical education. This view joins a growing field of research in the materiality of practice and everyday life, which embraces wide-ranging theoretical families that can only be briefly mentioned in this short introduction. The main premise they share is that social and material forces, culture, nature and technology, are enmeshed in everyday practice. Objects and humans act upon one another in ways that mutually transform their characteristics and activity. Examples from research in medical practice show how materials actively influence clinical practice, how learning itself is a material matter, how protocols are in fact temporary sociomaterial achievements, and how practices form unique and sometimes conflicting sociomaterial worlds, with diverse diagnostic and treatment approaches for the same thing. &nbsp; CONCLUSIONS The article concludes with implications for learning in practice. The shift is from sole emphasis on acquiring knowledge representations to learning how to participate more wisely in particular situations. Focus is on learning how to attune to minor material fluctuations and surprises, how to track one&rsquo;s own and other&rsquo;s effects on the &lsquo;intra-actions&rsquo; and emerging effects, and how to improvise solutions

Continuous hyperfractionated accelerated radiotherapy - Escalated dose (CHART-ED): A phase i study

Patients who present with locally advanced inoperable non-small cell lung cancer (NSCLC) may be suitable for radical radiotherapy. A randomised trial of 563 patients compared CHART and conventional radical radiotherapy (60 Gy/30f) given over 6 weeks and suggested that CHART resulted in a 9% improvement in 2-year survival (Saunders et al., 1999). RT dose escalation for both conventional and CHARTWEL (CHART-WeekEndLess) - fractionation schedules is feasible with modern 3-dimensional CT-based planning techniques and we initiated a phase I CHART dose escalation study in 2009. Methods Patients with WHO performance status 0-2 histologically confirmed, inoperable, stage I-III non-small cell lung cancer were recruited into an open phase I dose escalation trial. Three cohorts of six patients were recruited sequentially. Total dose was escalated from standard CHART radiotherapy of 54 Gy/36f/12 days to 57.6 Gy (2 × 1.8 Gy fractions on day 15, Group 1), 61.2 Gy (4 × 1.8 Gy fractions on days 15-16, Group 2) and 64.8 Gy (6 × 1.8 Gy fractions on days 15-17, Group 3). Results Between April 2010 and May 2012, 18 patients were enrolled from 5 UK centres and received escalated dose radiotherapy. 14 were male, 16 squamous cell histology and 12 were stage IIIA or IIIB. The median age was 70 years and baseline characteristics were similar across the three dose cohorts. One patient did not start escalated radiotherapy but all remaining patients completed their planned radiotherapy schedules. Of these 9 patients have died to date with a median survival of 2 years across the three cohorts. Grade 3 or 4 adverse events (fatigue, dysphagia, nausea and anorexia - classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) were reported in 6 patients but the pre-specified dose limiting toxicities (grade 4 early oesophagitis; grade 3 cardiac, spinal cord and pneumonitis) were not observed. Conclusions CHART remains a radiotherapy schedule in routine use across the UK and in this dose escalation study no dose limiting toxicities were observed. We feel the dose of 64.8 Gy/42f/17 days should be taken forward into further clinical trials. The sample size used in this study was small so we plan a randomised phase II study that includes other radiotherapy schedules to confirm safety and select an accelerated sequential chemo-radiotherapy schedule to take into phase III studies