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.

Water-hydrophobic compound interactions with the microbial cell

The structural interactions of biological macromolecules, their biochemical activities and, ultimately, the metabolic function of cellular systems are dependent upon weak inter- and intra-molecular forces such as hydrogen bonds, Van der Waals forces, and the hydrophobic effect. Water molecules, and those of hydrophobic substances such as hydrocarbons, can take part in and/or modify these interactions and thereby determine the operational and structural stability of the microbial cell and its macromolecular systems. We explain how the cytosol, plasma membrane and the extracellular solution form a material and energetic continuum; and discuss the behavior of hydrophobic substances of extracellular origin as they migrate into the plasma membrane and into the cell's interior. The adverse effects of substances with a log P octanol-water =2, that partition into the hydrophobic domains of biological macromolecules, are discussed in relation to microbial cell function; and we speculate whether the cellular stress that they induce is symmetrical or asymmetrical in nature. In the context of the microbial environment, we take a situational-functional approach to consider how hydrophobic stressors interact with the microbial cell, and what types of evasion tactics microbes can employ to minimize their inhibitory activities. Finally, we discuss the ecological implications of hydrocarbon-induced cellular stress for microbial systems.

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

An evaluation of the capability of a biolayer interferometry biosensor to detect low-molecular-weight food contaminants

The safety of our food is an essential requirement of society. One well-recognised threat is that of chemical contamination of our food, where low-molecular-weight compounds such as biotoxins, drug residues and pesticides are present. Low-cost, rapid screening procedures are sought to discriminate the suspect samples from the population, thus selecting only these to be forwarded for confirmatory analysis. Many biosensor assays have been developed as screening tools in food contaminant analysis, but these tend to be electrochemical, fluorescence or surface plasmon resonance based. An alternative approach is the use of biolayer interferometry, which has become established in drug discovery and life science studies but is only now emerging as a potential tool in the analysis of food contaminants. A biolayer interferometry biosensor was assessed using domoic acid as a model compound. Instrument repeatability was tested by simultaneously producing six calibration curves showing replicate repeatability (n = 2) ranging from 0.1 to 6.5 % CV with individual concentration measurements (n = 12) ranging from 4.3 to 9.3 % CV, giving a calibration curve midpoint of 7.5 ng/ml (2.3 % CV (n = 6)). Reproducibility was assessed by producing three calibration curves on different days, giving a midpoint of 7.5 ng/ml (3.4 %CV (n = 3)). It was further shown, using assay development techniques, that the calibration curve midpoint could be adjusted from 10.4 to 1.9 ng/ml by varying assay parameters before the simultaneous construction of three calibration curves in matrix and buffer. Sensitivity of the assay compared favourably with previously published biosensor data for domoic acid. © 2013 Springer-Verlag Berlin Heidelberg.

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.

The Pan-STARRS Moving Object Processing System

We describe the Pan-STARRS Moving Object Processing System (MOPS), a modern software package that produces automatic asteroid discoveries and identifications from catalogs of transient detections from next-generation astronomical survey telescopes. MOPS achieves >99.5% efficiency in producing orbits from a synthetic but realistic population of asteroids whose measurements were simulated for a Pan-STARRS4-class telescope. Additionally, using a nonphysical grid population, we demonstrate that MOPS can detect populations of currently unknown objects such as interstellar asteroids. MOPS has been adapted successfully to the prototype Pan-STARRS1 telescope despite differences in expected false detection rates, fill-factor loss, and relatively sparse observing cadence compared to a hypothetical Pan-STARRS4 telescope and survey. MOPS remains highly efficient at detecting objects but drops to 80% efficiency at producing orbits. This loss is primarily due to configurable MOPS processing limits that are not yet tuned for the Pan-STARRS1 mission. The core MOPS software package is the product of more than 15 person-years of software development and incorporates countless additional years of effort in third-party software to perform lower-level functions such as spatial searching or orbit determination. We describe the high-level design of MOPS and essential subcomponents, the suitability of MOPS for other survey programs, and suggest a road map for future MOPS development.

A review of topographic controls on moraine distribution

Ice-marginal moraines are often used to reconstruct the dimensions of former ice masses, which are then used as proxies for palaeoclimate. This approach relies on the assumption that the distribution of moraines in the modern landscape is an accurate reflection of former ice margin positions during climatically controlled periods of ice margin stability. However, the validity of this assumption is open to question, as a number of additional, nonclimatic factors are known to influence moraine distribution. This review considers the role played by topography in this process, with specific focus on moraine formation, preservation, and ease of identification (topoclimatic controls are not considered). Published literature indicates that the importance of topography in regulating moraine distribution varies spatially, temporally, and as a function of the ice mass type responsible for moraine deposition. In particular, in the case of ice sheets and ice caps ( > 1000 km2), one potentially important topographic control on where in a landscape moraines are deposited is erosional feedback, whereby subglacial erosion causes ice masses to become less extensive over successive glacial cycles. For the marine-terminating outlets of such ice masses, fjord geometry also exerts a strong control on where moraines are deposited, promoting their deposition in proximity to valley narrowings, bends, bifurcations, where basins are shallow, and/or in the vicinity of topographic bumps. Moraines formed at the margins of ice sheets and ice caps are likely to be large and readily identifiable in the modern landscape. In the case of icefields and valley glaciers (10–1000 km2), erosional feedback may well play some role in regulating where moraines are deposited, but other factors, including variations in accumulation area topography and the propensity for moraines to form at topographic pinning points, are also likely to be important. This is particularly relevant where land-terminating glaciers extend into piedmont zones (unconfined plains, adjacent to mountain ranges) where large and readily identifiable moraines can be deposited. In the case of cirque glaciers (< 10 km2), erosional feedback is less important, but factors such as topographic controls on the accumulation of redistributed snow and ice and the availability of surface debris, regulate glacier dimensions and thereby determine where moraines are deposited. In such cases, moraines are likely to be small and particularly susceptible to post-depositional modification, sometimes making them difficult to identify in the modern landscape. Based on this review, we suggest that, despite often being difficult to identify, quantify, and mitigate, topographic controls on moraine distribution should be explicitly considered when reconstructing the dimensions of palaeoglaciers and that moraines should be judiciously chosen before being used as indirect proxies for palaeoclimate (i.e., palaeoclimatic inferences should only be drawn from moraines when topographic controls on moraine distribution are considered insignificant).

Multiplication of microbes below 0.690 water activity: implications for terrestrial and extraterrestrial life

Since a key requirement of known life forms is available water (water activity; aw), recent searches for signatures of past life in terrestrial and extraterrestrial environments have targeted places known to have contained significant quantities of biologically available water. However, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water-activity. The lower limit of water activity that enables cell division appears to be ∼ 0.605 which, until now, was only known to be exhibited by a single eukaryote, the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, though, prokaryotic. Recent evidence now indicates that some halophilic Archaea and Bacteria have water-activity limits more or less equal to those of X. bisporus. We discuss water activity in relation to the limits of Earth's present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply close to the 0.605-aw limit; and whether extraterrestrial aqueous milieux of ≥ 0.605 aw can resemble fertile microbial habitats found on Earth.

Service user perspectives on palliative care education for health and social care professionals supporting people with learning disabilities

Background and objectives
Evidence from European and American studies indicates limited referrals of people with learning (intellectual) disabilities to palliative care services. Although professionals’ perceptions of their training needs in this area have been studied, the perceptions of people with learning disabilities and family carers are not known. This study aimed to elicit the views of people with learning disabilities, and their family carers concerning palliative care, to inform healthcare professional education and training.

Methods
A qualitative, exploratory design was used. A total of 17 people with learning disabilities were recruited to two focus groups which took place within an advocacy network. Additionally, three family carers of someone with a learning disability, requiring palliative care, and two family carers who had been bereaved recently were also interviewed.

Results
Combined data identified the perceived learning needs for healthcare professionals. Three subthemes emerged: ‘information and preparation’, ‘provision of care’ and ‘family-centred care’.

Conclusions
This study shows that people with learning disabilities can have conversations about death and dying, and their preferred end-of-life care, but require information that they can understand. They also need to have people around familiar to them and with them. Healthcare professionals require skills and knowledge to effectively provide palliative care for people with learning disabilities and should also work in partnership with their family carers who have expertise from their long-term caring role. These findings have implications for educators and clinicians.

Developing a best practice model for partnership practice between specialist palliative care and intellectual disability services: a mixed methods study

Background: The lack of access to good quality palliative care for people with intellectual disabilities is highlighted in the international literature. In response, more partnership practice in end-of-life care is proposed. 
Aim: This study aimed to develop a best practice model to guide and promote partnership practice between specialist palliative care and intellectual disability services. 
Design: A mixed methods research design involving two phases was used, underpinned by a conceptual model for partnership practice. 
Setting/participants: Phase 1 involved scoping end-of-life care to people with intellectual disability, based on self-completed questionnaires. In all, 47 of 66 (71.2%) services responded. In Phase 2, semi-structured interviews were undertaken with a purposive sample recruited of 30 health and social care professionals working in intellectual disability and palliative care services, who had provided palliative care to someone with intellectual disability. For both phases, data were collected from primary and secondary care in one region of the United Kingdom. 
Results: In Phase 1, examples of good practice were apparent. However, partnership practice was infrequent and unmet educational needs were identified. Four themes emerged from the interviews in Phase 2: challenges and issues in end-of-life care, sharing and learning, supporting and empowering and partnership in practice. 
Conclusion: Joint working and learning between intellectual disability and specialist palliative care were seen as key and fundamental. A framework for partnership practice between both services has been developed which could have international applicability and should be explored with other services in end-of-life care.

Manual mapping of drumlins in synthetic landscapes to assess operator effectiveness

Mapped topographic features are important for understanding processes that sculpt the Earth’s surface. This paper presents maps that are the primary product of an exercise that brought together 27 researchers with an interest in landform mapping wherein the efficacy and causes of variation in mapping were tested using novel synthetic DEMs containing drumlins. The variation between interpreters (e.g. mapping philosophy, experience) and across the study region (e.g. woodland prevalence) opens these factors up to assessment. A priori known answers in the synthetics increase the number and strength of conclusions that may be drawn with respect to a traditional comparative study. Initial results suggest that overall detection rates are relatively low (34–40%), but reliability of mapping is higher (72–86%). The maps form a reference dataset.

RNAi dynamics in Juvenile Fasciola spp. Liver flukes reveals the persistence of gene silencing in vitro

Background: Fasciola spp. liver fluke cause pernicious disease in humans and animals. Whilst current control is unsustainable due to anthelmintic resistance, gene silencing (RNA interference, RNAi) has the potential to contribute to functional validation of new therapeutic targets. The susceptibility of juvenile Fasciola hepatica to double stranded (ds)RNA-induced RNAi has been reported. To exploit this we probe RNAi dynamics, penetrance and persistence with the aim of building a robust platform for reverse genetics in liver fluke. We describe development of standardised RNAi protocols for a commercially-available liver fluke strain (the US Pacific North West Wild Strain), validated via robust transcriptional silencing of seven virulence genes, with in-depth experimental optimisation of three: cathepsin L (FheCatL) and B (FheCatB) cysteine proteases, and a σ-class glutathione transferase (FheσGST).

Methodology/Principal Findings: Robust transcriptional silencing of targets in both F. hepatica and Fasciola gigantica juveniles is achievable following exposure to long (200–320 nt) dsRNAs or 27 nt short interfering (si)RNAs. Although juveniles are highly RNAi-susceptible, they display slower transcript and protein knockdown dynamics than those reported previously. Knockdown was detectable following as little as 4h exposure to trigger (target-dependent) and in all cases silencing persisted for ≥25 days following long dsRNA exposure. Combinatorial silencing of three targets by mixing multiple long dsRNAs was similarly efficient. Despite profound transcriptional suppression, we found a significant time-lag before the occurrence of protein suppression; FheσGST and FheCatL protein suppression were only detectable after 9 and 21 days, respectively.

Conclusions/Significance: In spite of marked variation in knockdown dynamics, we find that a transient exposure to long dsRNA or siRNA triggers robust RNAi penetrance and persistence in liver fluke NEJs supporting the development of multiple-throughput phenotypic screens for control target validation. RNAi persistence in fluke encourages in vivo studies on gene function using worms exposed to RNAi-triggers prior to infection.