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Phosphoinositide-3-kinase (PI3K) inhibitors have efficacy in lymphoid malignancies; however, inflammatory and infectious toxicities can compromise the treatment course. An improved understanding of these toxicities will guide clinical use and further development. We evaluated the occurrence of treatment-related adverse events (AEs) in a retrospective review of 79 patients treated in standard fashion with PI3K inhibitor monotherapy or with anti-CD20 monoclonal antibodies or as part of a novel combination regimen. Patients treated with a novel combination were at a higher risk of developing a severe AE compared to those treated with standard therapy (HR 1.89, 95% CI 1.02, 3.49; p =.04). Additionally, previously untreated patients were at higher risk of developing a severe AE compared to previously treated patients (HR 3.19, 95% CI 1.48, 6.84; p =.003). These results caution against the use of untested PI3K inhibitor combinations in routine practice and suggest that early phase clinical trials should utilize conservative treatment schemas. [ABSTRACT FROM AUTHOR]

Four new neo-clerodanes, crotonolins C-F (3-6), were isolated from the stem bark of Croton oligandrus together with the known clerodane crotonzambefuran A, the abietanes 7-β-hydroxydehydroabietic acid and 7-oxodehydroabietic acid, and ferulic acid. Their structures were elucidated by spectroscopic analyses including 1D and 2D NMR and HRESIMS and by comparison with previously reported data. The cytotoxicity of the isolated compounds against A549, MCF7, PC3 and PNT2 cells was evaluated using the MTT assay. Only 7-β-hydroxydehydroabietic acid showed a moderate level of activity against PC3 cells with an IC50 value of 68.9 ± 6.6 µM. [ABSTRACT FROM AUTHOR]

The increasing global burden of Parkinson's disease (PD) poses a particular challenge for developing countries, such as Thailand, when delivering care to a geographically diverse populace with limited resources, often compounded by a lack of expertise in the use of certain PD medications, such as device-aided therapies (DAT). A panel of local, regional, and international PD experts convened to review the unmet needs of PD in Thailand and share insights into effective delivery of DAT, focusing on experience with apomorphine infusion. Despite its proven efficacy and safety, implementation of apomorphine infusion as a new option was not straightforward. This has prompted a range of health-care professional and patient-focused initiatives, led by the Chulalongkorn Center of Excellence for Parkinson's Disease and Related Disorders in Bangkok, to help establish a more coordinated approach to PD management throughout the country and ensure patients have access to suitable treatments. Overcoming the challenges of education, proficiency, resource capacity and standard of care for PD patients in developing countries requires a coordinated effort both nationally and beyond. The best practices identified in Thailand following the introduction of apomorphine infusion might be helpful for other countries when implementing similar programs. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is associated with increased risk for certain cancers, but relatively little is known about the risk for these patients to develop additional B cell malignancies. Here, we review the available epidemiological data on multiple B cell malignancies in CLL, discuss diagnostic methods and proper pathologic evaluation to distinguish CLL from other B cell malignancies, and address clinical challenges and unmet needs in caring for CLL patients with unrelated B cell malignancies and disease transformation. Considerations include CLL patients with unrelated monoclonal B cell lymphocytosis, biclonal CLL, secondary B cell non-Hodgkin lymphomas, and Richter syndrome – both clonally related transformation and de novo large B cell lymphoma. We address the challenges that remain in order to better understand the underlying risk factors and biology that may put CLL patients at increased risk of developing multiple B cell neoplasia. [ABSTRACT FROM AUTHOR]

Librarians and staff at a public university drew upon previous experience with instructional games to develop, implement, and assess a card game as a library orientation activity for new transfer students. This project was shaped by a desire to meet transfer students' unique needs as well as the logistical constraints associated with the university's transfer student orientation. The card game, modeled after Apples to Apples, presented information about the campus library system in a fun, informal way that allowed transfer students to socialize with each other while learning. Survey responses indicated that students found the game both enjoyable and helpful. [ABSTRACT FROM AUTHOR]

Gross flow data for workers moving between the states of employment, unemployment and non-participation in Australia can be used to analyse the likelihood of workers transitioning between the three states in different phases of the business cycle. We use correlation analysis and a SVAR model to determine the cyclicality of state transition rates and use these results to characterise labour force inflows and outflows as being consistent in aggregate with either the discouraged-worker effect (DWE) or the added-worker effect (AWE). We find evidence that the AWE is dominant in transitions in both directions between unemployment and non-participation which contributes to a rise in unemployment during economic contractions. We also find that the DWE is dominant in transitions from nonparticipation to employment and that this drives the overall result that non-participation rises during a contraction. This means that the overall participation rate is procyclical. It is important to understand the cyclical influences on labour force participation and its interaction with unemployment before framing policy responses which seek to reduce labour market slack. [ABSTRACT FROM AUTHOR]

Many multiregional input–output (MRIO) databases are used to calculate consumption-based accounts. Results feature in climate policy discussion on emissions reduction responsibilities; yet studies show that outcomes produced by each database differ. This paper compares the emissions associated with value chains from Eora, EXIOBASE, GTAP and WIOD. Structural path analysis identifies the largest paths in each database and the differences in common paths are calculated. For the top 100 value chain paths that contain the largest difference, structural path decomposition is used to identify the contribution each part of the value chain makes towards the difference. The results identify and quantify key flows that are the cause of difference in the databases. From these, we can conclude that key MRIO database construction decisions, such as using the residence or territorial principle for emissions allocation and whether energy spends are reallocated based on physical data, are the major causes of differences. [ABSTRACT FROM PUBLISHER]

ABSTRACT Glacier mass balance and mass balance gradient are fundamentally affected by changes in glacier 3D geometry. Few studies have quantified changing mountain glacier 3D geometry, not least because of a dearth of suitable spatiotemporally distributed topographical information. Additionally, there can be significant uncertainty in georeferencing of historical data and subsequent calculations of the difference between successive surveys. This study presents multiple 3D glacier reconstructions and the associated mass balance response of Kårsaglaciären, which is a 0.89 ± 0.01 km2 mountain glacier in sub-arctic Sweden. Reconstructions spanning 101 years were enabled by historical map digitisation and contemporary elevation and thickness surveys. By considering displacements between digitised maps via the identification of common tie-points, uncertainty in both vertical and horizontal planes were estimated. Results demonstrate a long-term trend of negative mass balance with an increase in mean elevation, total glacier retreat (1909-2008) of 1311 ± 12 m, and for the period 1926-2010 a volume decrease of 1.0 ± 0.3 × 10-3 km3 yr-1. Synthesising measurements of the glaciers' past 3D geometry and ice thickness with theoretically calculated basal stress profiles explains the present thermal regime. The glacier is identified as being disproportionately fast in its rate of mass loss and relative to area, is the fastest retreating glacier in Sweden. Our long-term dataset of glacier 3D geometry changes will be useful for testing models of the evolution of glacier characteristics and behaviour, and ultimately for improving predictions of meltwater production with climate change. [ABSTRACT FROM AUTHOR]

The social identity perspective asserts that it is the shared connection within a unified group that forms the foundation of successful group functioning. This is particularly salient during change. This review outlines the value and applicability of social identity principles in understanding change management. The first part of the article explains the underpinnings of resilient teams from a social identity perspective. In particular, the social identity approach is introduced, before the roles of shared and multiple contents in times of identity threat (e.g. during organizational change) are discussed. The second part of the article explains social identity strategies to build resilient teams in change contexts. In particular, the review focuses on the 3Rs approach (reflect, represent, and realize) as a developmental framework to create unique and distinctive social identities during change. Finally, a theoretical advancement of the 3Rs is proposed to include Reappraisal to optimize group and individual responses to the stress ubiquitous during change. [ABSTRACT FROM AUTHOR]

The purpose of this review is to demonstrate the applicability of a social identity approach to leadership in sporting contexts. A social identity approach to leadership contends that leaders and group members are connected through feeling a sense ofbelongingandemotional attachmentto their group. The present review (1) outlines the theoretical underpinnings of social identity theory, (2) reflects on the four principles of social identity leadership and applies them to sport, (3) contrasts social identity leadership with current leadership theories, and (4) provides suggestions for future research investigating a social identity approach to leadership in sport. Accordingly, the review illustrates how an appreciation of the social context and group members’ values allow leaders tomobilise– enlist the motivation and abilities of – athletes to achieve the leader’s vision. A social identity approach to leadership has the potential to extend understanding of leadership in sport by emphasising the role of groups and context in leadership. [ABSTRACT FROM PUBLISHER]

In order to examine the way ethical decisions are made, we asked ethicists, regulatory officials, and experienced researchers to review a set of scenarios that depict important ethical tensions in research. The method employed was "protocol analysis," a talk-aloud technique pioneered by cognitive scientists. Each individual was asked to make recommendations for courses of action. Later, we held a focus group of university faculty and staff with either institutional review board experience or research ethics training. They too were asked to recommend actions. The results show there are areas where the two data collection approaches agree, as well as areas of considerable difference. Implications for training in the responsible conduct of research are discussed. [ABSTRACT FROM AUTHOR]

The purpose of the present paper is to illustrate how leaders can create high performance environments. Using Team Great Britain (TeamGB) cycling’s performance director as a case example, we discuss how leaders can develop social identities (i.e. an emotional attachment and sense of belonging) and shape group meanings as mechanisms through which performance excellence can be achieved. We draw on a contemporary theory of leadership derived from organisational and social psychology to explain how leaders can act to strengthen the emotional bonds within their sport group and motivate athletes to embrace specific group meanings. The present paper also reflects on the lessons learnt from London 2012 that could inform leadership practice in preparation for Rio 2016. In particular, the leaders’ role in developing social identities and distinctive group meanings is important to create an environment conducive to optimum performance. In sum, a social identity approach to leadership detailed within the current paper provides a useful framework to help maximise the opportunities that TeamGB gleaned from London 2012 in order to deliver performance excellence again in Rio 2016. [ABSTRACT FROM PUBLISHER]

A selection of natural wonders in the Historia Brittonum folk history includes a seemingly peculiar tale involving a mysterious corpse and a levitating altar. This paper places the tale in the context of early medieval hagiography, and addresses its presence in the wonders listed by suggesting the altar's location and nature. [ABSTRACT FROM AUTHOR]

The natural wonders listed in the folk history known as the Historia Brittonum include Lake Liuan/Lliwan, the site of which is now lost despite featuring in folktales and topographies and containing a dramatic tidal whirlpool/fountain. We identify this key early-medieval wonder as the Whirlyholes, now inactive features near Caerwent, South Wales. [ABSTRACT FROM AUTHOR]

This article explores the capability of European Union law to 'organise' regionalism - in other words, to translate into legal process social demands in regions for greater autonomy from the central institutions of their state. The exploration involves examination of Treaty provisions, Union legislation, Court judgements and Commission decisions. The examination addresses problems of the relationship between legal and social space. It considers, in particular, the relationship between sovereignty-based definitions of space in EU law and the assumptions of the literature on multilevel governance. [ABSTRACT FROM AUTHOR]

Discusses the role of the Russian state and the Russian Orthodox Church (ROC) in the field of international relations. Main roots of ROC; Concepts of Holy Russia; Two major conflicts that involve the ROC in Ukraine; ROC's struggle to influence policy affecting ethnic Russians in Estonia; Religious and cultural links between Russia and Serbia.

This paper presents empirical results from five case‐studies of “on the road” commercial bus competition in Britain, and uses these results to test some economic theories relating to bus competition. There are no instances in the case‐studies of competition between different qualities of bus service, but there has been intense competition between buses offering similar qualities of service. The economic models of horizontal bus competition seem broadly consistent with the empirical results. However, the predictions of the models that competing buses will run at equal headways, and that fares will be lower on high‐demand routes than on low‐demand routes, are not borne out by the evidence; the reasons for this are discussed. The paper considers evidence that the bus market is contestable. The results are inconclusive, but the most telling single point is in favour of the theory that the market is contestable. [ABSTRACT FROM PUBLISHER]

This paper considers the way in which the risks of accidents are assessed by organizations concerned with the four main modes of transport: road, rail, civil aviation, and water transport. Risk assessment has two main components: risk estimation, which is the process of estimating what the risks are from an activity, and risk evaluation, which is the process of deciding or recommending what should be done about them. The paper discusses the methods and intellectual frameworks used for risk estimation and risk evaluation in each mode of transport. Conclusions are offered at the end, based on cross‐modal comparisons. [ABSTRACT FROM PUBLISHER]

The product of the von Hippel-Lindau gene (VHL) acts as the substrate-recognition component of an E3 ubiquitin ligase complex that ubiquitylates the catalytic α subunit of hypoxia-inducible factor (HIF) for oxygen-dependent destruction. Although emerging evidence supports the notion that deregulated accumulation of HIF upon the loss of VHL is crucial for the development of clear-cell renal cell carcinoma (CC-RCC), the molecular events downstream of HIF governing renal oncogenesis remain unclear. Here, we show that the expression of a homophilic adhesion molecule, E-cadherin, a major constituent of epithelial cell junctions whose loss is associated with the progression of epithelial cancers, is significantly down-regulated in primary CC-RCC and CC-RCC cell lines devoid of VHL. Reintroduction of wild-type VHL in CC-RCC (VHL-/-) cells markedly reduced the expression of E2 box-dependent E-cadherin-specific transcriptional repressors Snail and SIP1 and concomitantly restored E-cadherin expression. RNA interference-mediated knockdown of HIF α in CC-RCC (VHL-/-) cells likewise increased E-cadherin expression, while functional hypoxia or expression of VHL mutants incapable of promoting HIF α degradation attenuated E-cadherin expression, correlating with the disengagement of RNA polymerase II from the endogenous E-cadherin promoter/gene. These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin. [ABSTRACT FROM AUTHOR]