Causes of the rapid warming of the North Atlantic ocean in the mid-1990s

In the mid-1990s the subpolar gyre of the North Atlantic underwent a remarkable rapid warming, with sea surface temperatures increasing by around 1C in just 2 years. This rapid warming followed a prolonged positive phase of the North Atlantic Oscillation (NAO), but also coincided with an unusually negative NAO index in the winter of 1995/96. By comparing ocean analyses and carefully designed model experiments we show that this rapid warming can be understood as a delayed response to the prolonged positive phase of the NAO, and not simply an instantaneous response to the negative NAO index of 1995/96. Furthermore, we infer that the warming was partly caused by a surge, and subsequent decline, in the Meridional Overturning Circulation and northward heat transport of the Atlantic Ocean. Our results provide persuasive evidence of significant oceanic memory on multi-annual timescales, and are therefore encouraging for the prospects of developing skillful predictions.

Investigating the prevalence and causes of prescribing errors in general practice: the PRACtICe Study

Aim: To determine the prevalence and nature of prescribing errors in general practice; to explore the causes, and to identify defences against error. Methods: 1) Systematic reviews; 2) Retrospective review of unique medication items prescribed over a 12 month period to a 2% sample of patients from 15 general practices in England; 3) Interviews with 34 prescribers regarding 70 potential errors; 15 root cause analyses, and six focus groups involving 46 primary health care team members Results: The study involved examination of 6,048 unique prescription items for 1,777 patients. Prescribing or monitoring errors were detected for one in eight patients, involving around one in 20 of all prescription items. The vast majority of the errors were of mild to moderate severity, with one in 550 items being associated with a severe error. The following factors were associated with increased risk of prescribing or monitoring errors: male gender, age less than 15 years or greater than 64 years, number of unique medication items prescribed, and being prescribed preparations in the following therapeutic areas: cardiovascular, infections, malignant disease and immunosuppression, musculoskeletal, eye, ENT and skin. Prescribing or monitoring errors were not associated with the grade of GP or whether prescriptions were issued as acute or repeat items. A wide range of underlying causes of error were identified relating to the prescriber, patient, the team, the working environment, the task, the computer system and the primary/secondary care interface. Many defences against error were also identified, including strategies employed by individual prescribers and primary care teams, and making best use of health information technology. Conclusion: Prescribing errors in general practices are common, although severe errors are unusual. Many factors increase the risk of error. Strategies for reducing the prevalence of error should focus on GP training, continuing professional development for GPs, clinical governance, effective use of clinical computer systems, and improving safety systems within general practices and at the interface with secondary care.

The causes and effects of depreciation in office buildings: a ten year update

This paper publishes the results of the 1996 study, which repeats a cross-section analysis of around 125 City of London office buildings, and examines the longitudinal data contributed by a sample of 56 unrefurbished properties common to the 1986 and 1996 City of London datasets. An estimate of the average rate of rental and capital value depreciation is made; the effect of age is shown not to be straight-line; and the causes if depreciation are measured. The results are compared with the 1986 City of London findings.

Non-toxigenic Escherichia coli O157:H7 strain NCTC12900 causes attaching-effacing lesions and eae-dependent persistence in weaned sheep

Ruminants are regarded as a primary reservoir for Escherichia coli O157:H7, an important human pathogen. Intimin, encoded by the Locus of Enterocyte Effacement by E. coli O157:H7 organisms, has been cited as one bacterial mechanism of colonisation of the gastrointestinal tract. To confirm this and to test whether a non-toxigenic E. coli O157:H7 strain would colonise and persist in a sheep model, E. coli O157:H7 strain NCTC12900, that lacks Shiga toxin (stx) genes, was evaluated for use in a sheep model of persistence. Following oral inoculation of six-week-old sheep, persistent excretion of NCTC12900 was observed for up to 48 days. E. coli O157-associated attaching-effacing (AE) lesions were detected in the caecum and rectum of one six-week-old lamb, one day after inoculation. This is the first recorded observation of AE lesions in orally inoculated weaned sheep. Also, mean faecal excretion scores of NCTC12900 and an isogenic intimin (eae)-deficient mutant were determined from twenty-four six-week-old orally inoculated sheep. The eae mutant was cleared within 20 days and had lower mean excretion scores at all time points after day one post inoculation compared with the parental strain that was still being excreted at 48 days. Tissues were collected post mortem from animals selected at random from the study groups over the time course of the experiment. The eae mutant was detected in only 1/43 samples but the parental strain was recovered from 64/140 samples primarily from the large bowel although rumen, duodenum, jejunum, and ileum were culture positive especially from animals that were still excreting at and beyond 27 days after inoculation.

4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1

TRPA1 is an excitatory ion channel expressed by a subpopulation of primary afferent somatosensory neurons that contain substance P and calcitonin gene-related peptide. Environmental irritants such as mustard oil, allicin, and acrolein activate TRPA1, causing acute pain, neuropeptide release, and neurogenic inflammation. Genetic studies indicate that TRPA1 is also activated downstream of one or more proalgesic agents that stimulate phospholipase C signaling pathways, thereby implicating this channel in peripheral mechanisms controlling pain hypersensitivity. However, it is not known whether tissue injury also produces endogenous proalgesic factors that activate TRPA1 directly to augment inflammatory pain. Here, we report that recombinant or native TRPA1 channels are activated by 4-hydroxy-2-nonenal (HNE), an endogenous alpha,beta-unsaturated aldehyde that is produced when reactive oxygen species peroxidate membrane phospholipids in response to tissue injury, inflammation, and oxidative stress. HNE provokes release of substance P and calcitonin gene-related peptide from central (spinal cord) and peripheral (esophagus) nerve endings, resulting in neurogenic plasma protein extravasation in peripheral tissues. Moreover, injection of HNE into the rodent hind paw elicits pain-related behaviors that are inhibited by TRPA1 antagonists and absent in animals lacking functional TRPA1 channels. These findings demonstrate that HNE activates TRPA1 on nociceptive neurons to promote acute pain, neuropeptide release, and neurogenic inflammation. Our results also provide a mechanism-based rationale for developing novel analgesic or anti-inflammatory agents that target HNE production or TRPA1 activation.

Multi-year droughts in Europe: analysis of development and causes

Whilst hydrological systems can show resilience to short-term streamflow deficiencies during within-year droughts, prolonged deficits during multi-year droughts are a significant threat to water resources security in Europe. This study uses a threshold-based objective classification of regional hydrological drought to qualitatively examine the characteristics, spatio-temporal evolution and synoptic climatic drivers of multi-year drought events in 1962–64, 1975–76 and 1995–97, on a European scale but with particular focus on the UK. Whilst all three events are multi-year, pan-European phenomena, their development and causes can be contrasted. The critical factor in explaining the unprecedented severity of the 1975–76 event is the consecutive occurrence of winter and summer drought. In contrast, 1962–64 was a succession of dry winters, mitigated by quiescent summers, whilst 1995–97 lacked spatial coherence and was interrupted by wet interludes. Synoptic climatic conditions vary within and between multi-year droughts, suggesting that regional factors modulate the climate signal in streamflow drought occurrence. Despite being underpinned by qualitatively similar climatic conditions and commonalities in evolution and characteristics, each of the three droughts has a unique spatio-temporal signature. An improved understanding of the spatio-temporal evolution and characteristics of multi-year droughts has much to contribute to monitoring and forecasting capability, and to improved mitigation strategies.

The central European floods of August 2002: Part 2 - Synoptic causes and considerations with respect to climatic change

In the first part of this paper (Ulbrich et al. 2003), we gave a description of the August 2002 rainfall events and the resultant floods, in particular of the flood wave of the River Elbe. The extreme precipitation sums observed in the first half of the month were primarily associated with two rainfall episodes. The first episode occurred on 6/7 August 2002. The main rainfall area was situated over Lower Austria, the south-western part of the Czech Republic and south-eastern Germany. A severe flash flood was produced in the Lower Austrian Waldviertel (`forest quarter’ ). The second episode on 11± 13 August 2002 most severely affected the Erz Mountains and western parts of the Czech Republic. During this second episode 312mm of rain was recorded between 0600GMT on 12 August and 0600GMT on 13 August at the Zinnwald weather station in the ErzMountains, which is a new 24-hour record for Germany. The flash floods resulting from this rainfall episode and the subsequent Elbe flood produced the most expensive weatherrelated catastrophe in Europe in recent decades. In this part of the paper we discuss the meteorological conditions and physical mechanisms leading to the two main events. Similarities to the conditions that led to the recent summer floods of the River Oder in 1997 and the River Vistula in 2001 will be shown. This will lead us to a consideration of trends in extreme rainfall over Europe which are found in numerical simulations of anthropogenic climate change.

The causes of prescribing errors in English general practices: a qualitative study

Aim: To examine the causes of prescribing and monitoring errors in English general practices and provide recommendations for how they may be overcome. Design: Qualitative interview and focus group study with purposive sampling and thematic analysis informed by Reason’s accident causation model. Participants: General practice staff participated in a combination of semi-structured interviews (n=34) and six focus groups (n=46). Setting: Fifteen general practices across three primary care trusts in England. Results: We identified seven categories of high-level error-producing conditions: the prescriber, the patient, the team, the task, the working environment, the computer system, and the primary-secondary care interface. Each of these was further broken down to reveal various error-producing conditions. The prescriber’s therapeutic training, drug knowledge and experience, knowledge of the patient, perception of risk, and their physical and emotional health, were all identified as possible causes. The patient’s characteristics and the complexity of the individual clinical case were also found to have contributed to prescribing errors. The importance of feeling comfortable within the practice team was highlighted, as well as the safety of general practitioners (GPs) in signing prescriptions generated by nurses when they had not seen the patient for themselves. The working environment with its high workload, time pressures, and interruptions, and computer related issues associated with mis-selecting drugs from electronic pick-lists and overriding alerts, were all highlighted as possible causes of prescribing errors and often interconnected. Conclusion: This study has highlighted the complex underlying causes of prescribing and monitoring errors in general practices, several of which are amenable to intervention.

RNA interference suppression of genes in glycosyl transferase families 43 and 47 in wheat starchy endosperm causes large decreases in arabinoxylan content

The cell walls of wheat (Triticum aestivum) starchy endosperm are dominated by arabinoxylan (AX), accounting for 65% to 70% of the polysaccharide content. Genes within two glycosyl transferase (GT) families, GT43 (IRREGULAR XYLEM9 [IRX9] and IRX14) and GT47 (IRX10), have previously been shown to be involved in the synthesis of the xylan backbone in Arabidopsis, and close homologs of these have been implicated in the synthesis of xylan in other species. Here, homologs of IRX10 TaGT47_2 and IRX9 TaGT43_2, which are highly expressed in wheat starchy endosperm cells, were suppressed by RNA interference (RNAi) constructs driven by a starchy endosperm-specific promoter. The total amount of AX was decreased by 40% to 50% and the degree of arabinosylation was increased by 25% to 30% in transgenic lines carrying either of the transgenes. The cell walls of starchy endosperm in sections of grain from TaGT43_2 and TaGT47_2 RNAi transgenics showed decreased immunolabeling for xylan and arabinoxylan epitopes and approximately 50% decreased cell wall thickness compared with controls. The proportion of AX that was water soluble was not significantly affected, but average AX polymer chain length was decreased in both TaGT43_2 and TaGT47_2 RNAi transgenics. However, the long AX chains seen in controls were absent in TaGT43_2 RNAi transgenics but still present in TaGT47_2 RNAi transgenics. The results support an emerging picture of IRX9-like and IRX10-like proteins acting as key components in the xylan synthesis machinery in both dicots and grasses. Since AX is the main component of dietary fiber in wheat foods, the TaGT43_2 and TaGT47_2 genes are of major importance to human nutrition.

Simulation of late-twenty-first-century changes in wintertime atmospheric circulation over Europe due to anthropogenic causes

Evidence is presented, based on an ensemble of climate change scenarios performed with a global general circulation model of the atmosphere with high horizontal resolution over Europe, to suggest that the end-of-century anthropogenic climate change over the North Atlantic--European region strongly projects onto the positive phase of the North Atlantic Oscillation during wintertime. It is reflected in a doubling of the residence frequency of the climate system in the associated circulation regime, in agreement with the nonlinear climate perspective. The strong increase in the amplitude of the response, compared to coarse-resolution coupled model studies, suggests that improved model representation of regional climate is needed to achieve more reliable projections of anthropogenic climate change on European climate.

Care homes’ use of medicines study: prevalence, causes and potential harm of medication errors in care homes for older people

Introduction: Care home residents are at particular risk from medication errors, and our objective was to determine the prevalence and potential harm of prescribing, monitoring, dispensing and administration errors in UK care homes, and to identify their causes. Methods: A prospective study of a random sample of residents within a purposive sample of homes in three areas. Errors were identified by patient interview, note review, observation of practice and examination of dispensed items. Causes were understood by observation and from theoretically framed interviews with home staff, doctors and pharmacists. Potential harm from errors was assessed by expert judgement. Results: The 256 residents recruited in 55 homes were taking a mean of 8.0 medicines. One hundred and seventy-eight (69.5%) of residents had one or more errors. The mean number per resident was 1.9 errors. The mean potential harm from prescribing, monitoring, administration and dispensing errors was 2.6, 3.7, 2.1 and 2.0 (0 = no harm, 10 = death), respectively. Contributing factors from the 89 interviews included doctors who were not accessible, did not know the residents and lacked information in homes when prescribing; home staff’s high workload, lack of medicines training and drug round interruptions; lack of team work among home, practice and pharmacy; inefficient ordering systems; inaccurate medicine records and prevalence of verbal communication; and difficult to fill (and check) medication administration systems. Conclusions: That two thirds of residents were exposed to one or more medication errors is of concern. The will to improve exists, but there is a lack of overall responsibility. Action is required from all concerned.

NK1 receptor stimulation causes contraction and inositol phosphate increase in medium-size human isolated bronchi

Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size (approximately 1 mm in diameter) bronchi. Here, we have investigated the presence and biological responses of NK1 receptors in medium-size (2-5 mm in diameter) human isolated bronchi. Specific staining was seen in bronchial sections with an antibody directed against the human NK1 receptor. The selective NK1 receptor agonist, [Sar(9), Met(O2)(11)]SP, contracted about 60% of human isolated bronchial rings. This effect was reduced by two different NK1 receptor antagonists, CP-99,994 and SR 140333. Contraction induced by [Sar(9), Met(O2)(11)]SP was independent of acetylcholine and histamine release and epithelium removal, and was not affected by nitric oxide synthase and cyclooxygenase (COX) inhibition. [Sar(9), Met(O2)(11)]SP increased inositol phosphate (IP) levels, and SR 140333 blocked this increase, in segments of medium- and small-size (approximately 1 mm in diameter) human bronchi. COX inhibition blocked the IP increase induced by [Sar(9), Met(O2)(11)]SP in small-size, but not in medium-size, bronchi. NK1 receptors mediated bronchoconstriction in a large proportion of medium-size human bronchi. Unlike small-size bronchi this effect is independent of prostanoid release, and the results are suggestive of a direct activation of smooth muscle receptors and IP release.

The timing and causes of the Neolithic elm decline: new evidence from the Lower Thames Valley (London, UK)

Two new multi-proxy records of environmental change are provided from Horton Kirby Paper Mill and Old Seager Distillery in the Lower Thames Valley. Each site has evidence for a decline in elm woodland, which at Horton Kirby Paper Mill is recorded earlier than any other published record from the British Isles: sometime between 7320 and 7240 cal BP. Scolytus scolytus/S. multistriatus (the vectors for Dutch elm disease) are recorded after the decline in both sequences, adding to the number of sites with such evidence in the British Isles. Evidence of paludification and human activity are also recorded at the time of the elm decline reinforcing the multi-causal hypothesis. Integration of these results with 21 palaeoenvironmental records has produced a large number of well-dated, multiproxy records of the elm decline in this part of the UK. On the basis of this dataset, a classification system for categorising the relationships between the causal factors of the elm decline is proposed and recommended for future studies.