Cultural change in the FCA, PRA & Bank of England: Practising what they preach?

Our report examines how the culture of the financial regulators contributed to the financial crisis. It assesses the actions taken by the UK’s financial regulators to change their culture. It identifies the progress which has been made and the barriers encountered. To gather information we interviewed current and former staff at the regulators together with stakeholders from large and small financial institutions, consumer and SME groups and regulatory experts. The report includes the reactions from staff at the regulators to the cultural change programmes and the perceptions of external stakeholders

Informed Decisions for Actions in Maternal and Newborn Health 2010–17 Report What works, why and how in maternal and newborn health

IDEAS is a measurement, learning and evaluation project based at the London School of Hygiene & Tropical Medicine (LSHTM). The project aims to find out “what works, why, and how” for maternal and newborn health in three low-resource settings in Nigeria, India, and Ethiopia. The IDEAS team includes 20 research and professional support staff, living in Abuja, Addis Ababa, London, and New Delhi, who have been working since 2010 with the Bill & Melinda Gates Foundation (the foundation) and with the foundation’s implementation partners

Electronic structure of monoclinic BaBiO3

We present the results of photoemission studies of ‘‘valence disordered’’ monoclinic BaBiO3 in the photon energy range 15–120 eV. The line‐shapes of the valence band photoemission spectra and the Ba contributions to the valence band are very similar to the line shapes of the total density of states and Ba partial density of states, respectively. Oxygen resonance is observed, demonstrating the existence of empty O 2p states. These results support a more covalent rather than a simple ionic picture for the electronic states of BaBiO3.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87627/2/30_1.pd

No high Tibetan Plateau until the Neogene

The Late Paleogene surface height and paleoenvironment for the core area of the Qinghai-Tibetan Plateau (QTP) remain critically unresolved. Here, we report the discovery of the youngest well-preserved fossil palm leaves from Tibet. They were recovered from the Late Paleogene (Chattian), ca. 25.5 ± 0.5 million years, paleolake sediments within the Lunpola Basin (32.033°N, 89.767°E), central QTP at a present elevation of 4655 m. The anatomy of palms renders them intrinsically susceptible to freezing, imposing upper bounds on their latitudinal and altitudinal distribution. Combined with model-determined paleoterrestrial lapse rates, this shows that a high plateau cannot have existed in the core of Tibet in the Paleogene. Instead, a deep paleovalley, whose floor was 4 km) high mountain systems, formed a topographically highly varied landscape. This finding challenges prevailing views on tectonic processes, monsoon dynamics, and the evolution of Asian biodiversity

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

Purpose To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours.

PATRIOT is a phase I study of the ATR inhibitor, AZD6738, as monotherapy, and in combination with palliative radiotherapy. Here, we describe the protocol for this study, which opened in 2014 and is currently recruiting and comprises dose escalation of both drug and radiotherapy, and expansion cohorts

Influence of the Tibetan Plateau uplift on the Asian monsoon-arid environment evolution

As one of the most important geological events in Cenozoic era, the uplift of the Tibetan Plateau (TP) has had profound influences on the Asian and global climate and environment evolution. During the past four decades, many scholars from China and abroad have studied climatic and environmental effects of the TP uplift by using a variety of geological records and paleoclimate numerical simulations. The existing research results enrich our understanding of the mechanisms of Asian monsoon changes and interior aridification, but so far there are still a lot of issues that need to be thought deeply and investigated further. This paper attempts to review the research on the influence of the TP uplift on the Asian monsoon-arid environment, summarize three types of numerical simulations including bulk-plateau uplift, phased uplift and sub-regional uplift, and especially to analyze regional differences in responses of climate and environment to different forms of tectonic uplifts. From previous modeling results, the land-sea distribution and the Himalayan uplift may have a large effect in the establishment and development of the South Asian monsoon. However, the formation and evolution of the monsoon in northern East Asia, the intensified dryness north of the TP and enhanced Asian dust cycle may be more closely related to the uplift of the main body, especially the northern part of the TP. In this review, we also discuss relative roles of the TP uplift and other impact factors, origins of the South Asian monsoon and East Asian monsoon, feedback effects and nonlinear responses of climatic and environmental changes to the plateau uplift. Finally, we make comparisons between numerical simulations and geological records, discuss their uncertainties, and highlight some problems worthy of further studying

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Recent Advances in Understanding Particle Acceleration Processes in Solar Flares

We review basic theoretical concepts in particle acceleration, with particular emphasis on processes likely to occur in regions of magnetic reconnection. Several new developments are discussed, including detailed studies of reconnection in three-dimensional magnetic field configurations (e.g., current sheets, collapsing traps, separatrix regions) and stochastic acceleration in a turbulent environment. Fluid, test-particle, and particle-in-cell approaches are used and results compared. While these studies show considerable promise in accounting for the various observational manifestations of solar flares, they are limited by a number of factors, mostly relating to available computational power. Not the least of these issues is the need to explicitly incorporate the electrodynamic feedback of the accelerated particles themselves on the environment in which they are accelerated. A brief prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011