Management of Barrett's esophagus in the UK: Overtreated and underbiopsied but improved by the introduction of a national randomized trial

OBJECTIVES: To assess the variation in practice of Barrett's esophagus (BE) management in comparison with accepted international guidelines before and after the introduction of a large BE randomized controlled trial (RCT) with protocols including those of tissue sampling.
DESIGN: A validated anonymized questionnaire was sent to 401 senior attending gastroenterologists asking for details of their current management of BE, especially histological sampling. Of the 228 respondents, 57 individuals (each from a different center) were in the first group to enter the ASPirin Esomeprazole (BE) Chemoprevention Trial (AspECT), and we assessed change in practice in these centers.
RESULTS: Ninety percent of specialists did not take adequate biopsies for histological diagnosis. Furthermore, 74% would consider aggressive surgical resection for prevalent cases of high-grade dysplasia in BE as their first-line choice despite the associated perioperative mortality. Ninety-two percent claim their lack of adherence to guidelines is because there is a need for stronger evidence for surveillance and medical interventions. Effect of the AspECT trial: Those clinicians in centers where the AspECT trial has started have improved adherence to ACG guidelines compared with their previous practice (P < 0.05). BE patients now get 18.8% more biopsies compared with previous practice, and 37.7% if the patient is entered into the AspECT trial (P < 0.01).
CONCLUSIONS: This large study indicates both wide variation in practice and poor compliance with guidelines. Because optimal histology is arguably the most important facet of BE management, the improvement in practice in centers taking part in the AspECT trial indicates an additional value of large international RCTs.

Palaeoglacial and palaeoclimatic conditions in the NW Pacific, as revealed by a morphometric analysis of cirques upon the Kamchatka Peninsula

The distribution of glacial cirques upon the Kamchatka peninsula, Far Eastern Russia, is systematically mapped from satellite images and digital elevation model data. A total of 3,758 cirques are identified, 238 of which are occupied by active glaciers. The morphometry of the remaining 3,520 cirques is analysed. These cirques are found to show a very strong N bias in their azimuth (orientation), likely resulting from aspect-related variations in insolation. The strength of this N bias is considered to indicate that former glaciation upon the peninsula was often ‘marginal’, and mainly of cirque-type, with peaks extending little above regional equilibrium-line altitudes. This is supported by the fact that S and SE-facing cirques are the highest in the dataset, suggesting that glacier-cover was rarely sufficient to allow S and SE-facing glaciers to develop at low altitudes. The strength of these azimuth-related variations in cirque altitude is thought to reflect comparatively cloud-free conditions during former periods of glaciation. It is suggested that these characteristics, of marginal glaciation and comparatively cloud-free conditions, reflect the region’s former aridity, which was likely intensified at the global Last Glacial Maximum, and during earlier periods of ice advance, as a result of the development of negative pressure anomalies over the North Pacific (driven by the growth of the Laurentide Ice Sheet), combined with other factors, including an increase in the extent and duration of sea ice, a reduction in global sea levels, cooler sea surface temperatures, and the localised growth of mountain glaciers. There is published evidence to suggest extensive glaciation of the Kamchatka Peninsula at times during the Late Quaternary, yet the data presented here appears to suggest that such phases were comparatively short-lived, and that smaller cirque-type glaciers were generally more characteristic of the period.

End-of-Life care and people with intellectual disabilities: A multi-media educational resource

Aim This study aimed to develop and evaluate a multi-media educational resource in palliative and end-of-life care for specialist palliative care and intellectual disability services which promoted collaborative working. Methods: A mixed methods design involving three phases was used. Qualitative data were obtained from semi-structured interviews with a purposive sample of professionals (n=30) and family carers (n=5) and from two focus groups with people with intellectual disabilities (n=17). Data were content analysed as outlined y Newell and Burnard (2006). This identified training needs and issues, in end-of-life care for this population which were confirmed through quantitative data from services in a regional scoping study analysed using descriptive statistics. A DVD and manual were developed and evaluated with twelve professionals. Data were collected using a solicited diary, the Readiness for Inter-professional Learning Scale, Likert Scales and an evaluation questionnaire. Thematic analysis and descriptive statistics appropriate to data were used.Results: Findings suggest that this resource demonstrates the need for and benefits of partnership working and transferability of this learning to practice could address issues at end-of-life for people with intellectual disabilities. Conclusions: Findings of this study have importance for partnership working and service provision in end-of-life care for this population.

Pleistocene and Holocene glacier fluctuations upon the Kamchatka Peninsula

This review summarises landform records and published age-estimates (largely based upon tephrochronology) to provide an overview of glacier fluctuations upon the Kamchatka Peninsula during the Holocene and, to a lesser degree, earlier phases of glaciation. The evidence suggests that following deglaciation from the Last Glacial Maximum (LGM), the peninsula experienced numerous phases of small-scale glacial advance. During the Late Glacial, moraine sequences appear to reflect the former presence of extensive glaciers in some parts of the peninsula, though little chronological control is available for deposits of this period. During the Holocene, the earliest and most extensive phase of advance likely occurred sometime prior to c. 6.8 ka, when glaciers extended up to 8 km beyond their current margins. However, these deposits lack maximum age constrains, and pre-Holocene ages cannot be discounted. Between c. 6.8 ka and the onset of ‘Neoglaciation’ c. 4.5 ka, there is little evidence of glacial advance upon the peninsula, and this period likely coincides with the Holocene climatic optimum (or ‘hypsithermal’). Since c. 4.5 ka, numerous moraines have been deposited, likely reflecting a series of progressively less extensive phases of ice advance during the Late Holocene. The final stage of notable ice advance occurred during the Little Ice Age (LIA), between c. 1350 and 1850 C.E., when reduced summer insolation in the Northern Hemisphere likely coincided with solar activity minima and several strong tropical volcanic eruptions to induce widespread cooling. Following the LIA, glaciers upon the peninsula have generally shown a pattern of retreat, with accelerated mass loss in recent decades. However, a number of prominent climatically and non-climatically controlled glacial advances have also occurred during this period. In general, there is evidence to suggest that millennial scale patterns in the extent and timing of glaciation upon the peninsula (encompassing much of the last glacial period) are governed by the extent of ice sheets in North America. Millennial-to-centennial scale fluctuations of Kamchatkan glaciers (encompassing much of the Holocene) are governed by the location and relative intensity of the Aleutian Low and Siberian High pressure systems. Decadal scale variations in glacier extent and mass balance (particularly since the LIA) are governed by inter-decadal climatic variability over the North Pacific (as reflected by the Pacific Decadal Oscillation), alongside a broader trend of hemispheric warming.

Testing the efficacy of the glacial buzzsaw: insights from the Sredinny Mountains, Kamchatka

Peak altitudes, hypsometry, geology, and former equilibrium-line altitudes (ELAs) are analyzed across the Sredinny Mountains (Kamchatka). Overall, evidence is found to suggest that the glacial buzzsaw has operated to shape the topography of this mountain range, but the strength of this signature is not spatially uniform. In the southern sector of the mountains, we see evidence that an efficient glacial buzzsaw has acted to impose constraints upon topography, limiting peak altitudes, and concentrating land-surface area (hypsometric maxima) close to palaeo-ELAs. By contrast, in the northern sector of the mountains, a number of peaks rise high above the surrounding topography, and land-surface area is concentrated well below palaeo-ELAs. This deviation from a classic ‘buzzsaw signature’, in the northern sector of the mountains, is considered to reflect volcanic construction during the Quaternary, resulting in a series of high altitude peaks, combined with the action of dynamic glaciers, acting to skew basin topography toward low altitudes, well below palaeo-ELAs. These glaciers are considered to have been particularly dynamic because of their off-shore termination, their proximity to moisture-bearing air masses from the North Pacific, and because accumulation was supplemented by snow and ice avalanching from local high altitude peaks. Overall, the data suggest that the buzzsaw remains a valid mechanism to generally explain landscape evolution in mountain regions, but its signature is significantly weakened in mountain basins that experience both volcanic construction and climatic conditions favouring dynamic glaciation.

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism. © 2012 Macmillan Publishers Limited

Public knowledge and perceptions of connected health

Rationale, aims and objectives: This study aims to examine the public's knowledge and perceptions of connected health (CH).

Methods: A structured questionnaire was administered by face-to-face interview to an opportunistic sample of 1003 members of the public in 11 shopping centres across Northern Ireland (NI). Topics included public knowledge of CH, opinions about who should provide CH and views about the use of computers in health care. Multivariable analyses were conducted to assess respondents' willingness to use CH in the future.

Results: Sixty-seven per cent of respondents were female, 31% were less than 30 years old and 22% were over 60 years. Most respondents had never heard of CH (92%). Following a standard definition, the majority felt CH was a good idea (≈90%) and that general practitioners were in the best position to provide CH; however, respondents were equivocal about reductions in health care professionals' workload and had some concerns about the ease of device use. Factors positively influencing willingness to use CH in the future included knowledge of someone who has a chronic disease, residence in NI since birth and less concern about the use of information technology (IT) in health care. Those over 60 years old or who felt threatened by the use of IT to store personal health information were less willing to use CH in the future.

Conclusion: Increased public awareness and education about CH is required to alleviate concerns and increase the acceptability of this type of care.