Proton pump inhibitors and histamine-2-receptor antagonists and pancreatic cancer risk: a nested case-control study

Background: The relationship between use of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H₂RAs) and pancreatic cancer risk has yet to be examined. Data from a range of studies suggest biologically plausible mechanisms, whereby these drugs (or the conditions for which they are prescribed) may affect pancreatic cancer risk. The objective of this study was to investigate the relationship between use of PPIs/H₂RAs and pancreatic cancer risk.

Methods: A nested case – control study was conducted within the UK general practice research database (GPRD). Cases had a diagnosis of exocrine pancreatic cancer and controls were matched to cases on general practice site, sex and year of birth. Exposure to PPIs and to H₂RAs since entry into GPRD until 2 years before the diagnosis date (corresponding date in controls) and in the 5 years before the diagnosis date were separately assessed. Conditional logistic regression analyses were used to generate odds ratios (ORs) and 95% confidence intervals (CIs) associated with PPI or H₂RA use compared with nonuse.

Results: Ever use of PPIs since entry into the GPRD (excluding the 2 years prior to diagnosis) was not associated with risk of pancreatic cancer; OR (95% CI) 1.02 (0.85 – 1.22). Neither the dose nor the duration of PPI or H₂RA use was associated with pancreatic cancer risk. No consistent patterns of association were seen when cumulative exposure (dose and duration) to these drugs was examined separately or together.

Conclusion: PPI/H₂RA use, in a UK population, was not associated with pancreatic cancer risk.

Environmental and genetic control of arsenic accumulation and speciation in rice grain:comparing a range of common cultivars grown in contaminated sites across Bangladesh, China, and India

The concentration of arsenic (As) in rice grains has been identified as a risk to human health. The high proportion of inorganic species of As (As(i)) is of particular concern as it is a nonthreshold, class 1 human carcinogen. To be able to breed rice with low grain As, an understanding of genetic variation and the effect of different environments on genetic variation is needed. In this study, 13 cultivars grown at two field sites each in Bangladesh, India, and China are evaluated for grain As. There was a significant site, genotype, and site by genotype interaction for total grain As. Correlations were observed only between sites in Bangladesh and India, not between countries or within the Chinese sites. For seven cultivars the As was speciated which revealed significant effects of site, genotype, and site by genotype interaction for percentage As(i). Breeding low grain As cultivars that will have consistently low grain As and low As(i), over multiple environments using traditional breeding approaches may be difficult, although CT9993-5-10-1-M, Lemont, Azucena, and Te-qing in general had low grain As across the field sites.

The Palisades is a key reference site for the middle Pleistocene of eastern Beringia: New evidence from paleomagnetics and regional tephrostratigraphy

The Palisades, in central Alaska, is one of the most prominent exposures of Quaternary sediments on the Yukon River. Perennially-frozen silt and sand at the Palisades are presently thought to preserve paleoenvironmental records from the Holocene to ~Marine Isotope Stage (MIS) 8 and, beneath a major unconformity, the earliest Pleistocene (~2 Ma). We present new paleomagnetic and tephrochronologic constraints that substantially revise the age of the sediments at the Palisades. We describe 15 new tephra beds, including five beds below the prominent PAL tephra that correlate to known tephra with independent age control from other sites in eastern Beringia. These five known tephra include Chester Bluff tephra, which is present in east-central Alaska and the Yukon, and the newly named Alyeska Pipeline and Taylor Highway tephra from central Alaska; all are constrained to the middle Pleistocene. Paleomagnetic transects from the base of the bluff to the MIS 5e forest bed yield normal polarity, with the exception of a brief reversal event between Old Crow tephra (124 ± 10 ka) and the MIS 5e forest bed that is likely the first documentation of the Blake paleomagnetic event in Alaskan loess. The detailed tephrostratigraphy and paleomagnetic data collectively suggest that most of the sedimentary record at the Palisades is middle Pleistocene in age. The Palisades thus preserves a rare record of late to middle Pleistocene paleoenvironments with multiple regionally distributed tephra beds. © 2013 Elsevier Ltd.

Ser6 in the maize actin-depolymerizing factor, ZmADF3, is phosphorylated by a calcium-stimulated protein kinase and is essential for the control of functional activity

Maize actin-depolymerizing factor, ZmADF, binds both G- and F-actin and enhances in vitro actin dynamics. Evidence from studies on vertebrate ADF/cofilin supports the view that this class of protein responds to intracellular and extracellular signals and causes actin reorganization. As a test to determine whether such signal-responsive pathways existed in plants, this study addressed the ability of maize ADF to be phosphorylated and the likely effects of such phosphorylation on its capacity to modulate actin dynamics. It is shown that maize ADF3 (ZmADF3) can be phosphorylated by a calcium-stimulated protein kinase present in a 40-70% ammonium sulphate fraction of a plant cell extract. Phosphorylation is shown to be on Ser6, which is only one of nine amino acids that are fully conserved among the ADF/cofilin proteins across distantly related species. In addition, an analogue of phosphorylated ZmADF3 created by mutating Ser6 to Asp6 (zmadf3-4) does not bind G- or F-actin and has little effect on the enhancement of actin dynamics. These results are discussed in context of the previously observed actin reorganization in root hair cells.

An allelic series reveals essential roles for FY in plant development in addition to flowering-time control.

The autonomous pathway functions to promote flowering in Arabidopsis by limiting the accumulation of the floral repressor FLOWERING LOCUS C (FLC). Within this pathway FCA is a plant-specific, nuclear RNA-binding protein, which interacts with FY, a highly conserved eukaryotic polyadenylation factor. FCA and FY function to control polyadenylation site choice during processing of the FCA transcript. Null mutations in the yeast FY homologue Pfs2p are lethal. This raises the question as to whether these essential RNA processing functions are conserved in plants. Characterisation of an allelic series of fy mutations reveals that null alleles are embryo lethal. Furthermore, silencing of FY, but not FCA, is deleterious to growth in Nicotiana. The late-flowering fy alleles are hypomorphic and indicate a requirement for both intact FY WD repeats and the C-terminal domain in repression of FLC. The FY C-terminal domain binds FCA and in vitro assays demonstrate a requirement for both C-terminal FY-PPLPP repeats during this interaction. The expression domain of FY supports its roles in essential and flowering-time functions. Hence, FY may mediate both regulated and constitutive RNA 3'-end processing.

The sympathetic release test: a test used to assess thermoregulation and autonomic control of blood flow

When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the subject is gently heated by placing the feet and calves in a commercially available foot warming pouch or immersing the feet and calves in warm water and wrapping the subject in blankets. Skin blood flow is estimated from measurements of skin temperature in the fingers. Normally skin temperature of the fingers is 65-75 degrees F in cool conditions (environmental temperature: 59-68 degrees F) and rises to 85-95 degrees F during body heating. Deviations in this pattern may mean that there is abnormal sympathetic vasoconstrictor control of skin blood flow. Abnormal skin blood flow can substantially impair an individual's ability to thermoregulate and has important clinical implications. During whole body heating, the skin temperature from three different skin sites is monitored and oral temperature is monitored as an index of core temperature. Students determine the fingertip temperature at which the reflex release of sympathetic activity occurs and its maximal attainment, which reflects the vasodilating capacity of this cutaneous vascular bed. Students should interpret typical sample data for certain clinical conditions (Raynaud's disease, peripheral vascular disease, and postsympathectomy) and explain why there may be altered skin blood flow in these disorders.

A statistical process control approach for automatic anti-islanding detection using synchrophasors

Anti-islanding protection is becoming increasingly important due to the rapid installation of distributed generation from renewable resources like wind, tidal and wave, solar PV, bio-fuels, as well as from other resources like diesel. Unintentional islanding presents a potential risk for damaging utility plants and equipment connected from the demand side, as well as to public and personnel in utility plants. This paper investigates automatic islanding detection. This is achieved by deploying a statistical process control approach for fault detection with the real-time data acquired through a wide area measurement system, which is based on Phasor Measurement Unit (PMU) technology. In particular, the principal component analysis (PCA) is used to project the data into principal component subspace and residual space, and two statistics are used to detect the occurrence of fault. Then a fault reconstruction method is used to identify the fault and its development over time. The proposed scheme has been used in a real system and the results have confirmed that the proposed method can correctly identify the fault and islanding site.

Optimal wafer site selection using forward selection component analysis

Reducing wafer metrology continues to be a major target in semiconductor manufacturing efficiency initiatives due to it being a high cost, non-value added operation that impacts on cycle-time and throughput. However, metrology cannot be eliminated completely given the important role it plays in process monitoring and advanced process control. To achieve the required manufacturing precision, measurements are typically taken at multiple sites across a wafer. The selection of these sites is usually based on a priori knowledge of wafer failure patterns and spatial variability with additional sites added over time in response to process issues. As a result, it is often the case that in mature processes significant redundancy can exist in wafer measurement plans. This paper proposes a novel methodology based on Forward Selection Component Analysis (FSCA) for analyzing historical metrology data in order to determine the minimum set of wafer sites needed for process monitoring. The paper also introduces a virtual metrology (VM) based approach for reconstructing the complete wafer profile from the optimal sites identified by FSCA. The proposed methodology is tested and validated on a wafer manufacturing metrology dataset. © 2012 IEEE.

Acidity compensation of electrochemical measurements for on-site monitoring of heavy metals

This paper presents an electrochemical instrumentation system capable of real-time in situ detection of heavy metals. A practical approach to introduce acidity compensation against changes in amplitude of the peak currents is also presented. The compensated amplitudes can then be used to predict the concentration level of heavy metals. The system uses differential pulse anodic stripping voltammetry, which is a precise and sensitive analytical method with excellent limits of detection. The instrument is capable of detecting lead, cadmium, zinc, nickel and copper with good sensitivity and precision. The system avoids expensive and time-consuming procedures and may be used in a variety of situations to help environmental assessment and control. 

On-site monitoring and cartographical mapping of heavy metals

This paper presents a portable electrochemical instrument capable of real-time in situ detection and automatic identification of heavy metals. The instrument is equipped with an embedded Geographical Position System and is capable of storing the geographical position of the sample under test. Software has been developed to combine pollutant results with geographical position, in order to produce a cartographical presentation of the pollution of an area. The electrochemical instrument provides the facilities found in a traditional lab based instrument in a portable design for on-site measurements. The instrument is capable of detecting lead, cadmium, zinc, nickel, mercury, and copper with good sensitivity and precision. The system is reliable, easy to use, safe, and it may be used in a variety of situations to help environmental assessment and control.

SWAT-1: The effectiveness of a 'site visit' intervention on recruitment rates in a multi-centre randomised trial

Background: Recruitment rates in multi-centre randomised trials often fall below target recruitment rates, causing problems for study outcomes. The Studies Within A Trial (SWAT) Programme, established by the All-Ireland Hub for Trials Methodology Research in collaboration with the Medical Research Council Network of Hubs in the United Kingdom and others, is developing methods for evaluating aspects of trial methodology through the conduct of research within research. A recently published design for a SWAT-1 provides a protocol for evaluating the effect of a site visit by the principal investigator on recruitment in multi-centre trials.

Methods: Using the SWAT-1 design, the effect of a site visit, with the sole purpose of discussing trial recruitment, on recruitment rates in a large multicentre trial in the Republic of Ireland was evaluated. A controlled before and after intervention comparison was used, where the date of the site visit provides the time point for the intervention, and for the comparison to control sites. Site A received the intervention. Site B and Site C acted as the controls. Z-scores for proportions were calculated to determine within site recruitment differences. Odds ratios and 95% confidence intervals were calculated to determine between site recruitment differences.

Results: Recruitment rates were increased in Site A post-intervention (17% and 14% percentage point increases at 1 and 3 months, respectively). No differences in recruitment occurred in Site B or in Site C. Comparing between site differences, at 3 months post-intervention, a statistically significant difference was detected in favour of higher recruitment in Site A (34% versus 25%; odds ratio 1.57, 95% confidence interval 1.09 to 2.26).

Conclusions: This is the first reported example of a study in the SWAT programme.. It provides evidence that a site visit, combined with a scheduled meeting, increases recruitment in a clinical trial. Using this example, other researchers might be encouraged to consider conducting a similar study, allowing the findings of future SWAT-1s to be compared and combined, so that higher level evidence on the effect of a site visit by the principal investigator can be obtained.

Nong Thale Pron - a key site from southern Thailand for studying monsoon variability during the past 15000 years

Studies of marine sediments, cave speleothemes, annually laminated corals, and tree rings from Asian monsoon regions have added knowledge to our understanding of the factors that control inter-annual to millennial monsoon variability in the past and have provided important constraints for climate modeling scenarios. In contrast, the spatial and temporal pattern of sub-millennial scale monsoon variability and its impact on land cover in SE Asia are still unresolved. This shortcoming stems from the fact that temporally well-resolved paleo-environmental studies are missing from large parts of SE Asia, especially from Thailand. Given that global and regional climate models are increasingly using terrestrial paleo- data to test their performance, past changes in land cover are therefore important variables to better understand feedbacks between different Earth systems. We obtained sediments from Lake Nong Thale Pron, in southern Thailand (8º 10`N, 99 º23`E; 380 m.asl). The aim of our study is to reconstruct lake status changes and to evaluate whether the extent of these changes are linked to known shifts in monsoon intensity and variability. Preliminary results show that lake infilling started more than 15,000 years ago and that the sediments cover the last deglaciation and the Holocene. Current analyses include Itrax XRF core scanning, loss-on-ignition (LOI at 950 and 550ºC), CN elemental and isotopic composition. We expect that our results will be able to give a picture of how the lake's status has changed over time and whether the extent of these changes is linked to known shifts in monsoon intensity and variability.

Contested urbanism: Access and control issues in Tundikhel, Kathmandu

Contested Open Spaces?: Access and control issues in Tundikhel, Kathmandu

Public spaces play a role of political, economic and cultural transformation of cities and the impact of these transformations on the nature of public space.

Urban open space(s) in Kathmandu have been an important part of the city’s urbanism. Historically they have played an important role in the city as spaces for religious, cultural, social and political and military activities during the 300 years of unified monarchy. Throughout the civil war period (Maoist insurgency between 1996 and 2006) they became material locations for political activities, and a site for protests and dharnas. In post-conflict Kathmandu, especially since the abolition of Monarchy in May 28, 2008, these spaces are increasingly seen being claimed by street hawkers, informal sellers and individuals reflecting a new set of users and functions, whereas a significant part of Tundikhel still remains under the military occupation posing important questions around access, identity and control of an important space.


Public spaces are broadly defined as crossroads where different paths and trajectories meet, sometimes overlapping and other times colliding (Madanipour, 2003). Using Tudikhel in Kathmandu, this research examines the increasing collision and contestations witnessed through social, political and neoliberal interactions. It explores how spaces are constantly
contested, negotiated and as a result reshaped through these interactions. It is observed that multiple forces are at play to gain control and access of this important open space, leading to increasing fragmentation of the space, and erosion of its historic significance both as cultural venue and a symbol of democracy in modern Nepal. It is argued that increasing disconnection of Tudikhel from wider urban setting has contributed to exacerbation of these contestations

GIS on tourism planning: preventing the impacts caused by the developing tourism activity in a specific site

The environment is one of the greatest concerns of humankind. Nowadays, the activities which improve or destroy it must be assessed and controlled by efficient means which should permit the control of environmental impact caused by the development of these activities. This document presents an information system implementation, as a Decision Support system, allowing the Decision Maker to evaluate, foresee and control the future environmental impact of Tourism through consultation, the management and the presentation of decision schemes based on defined measures of a regional tourism planning.