The potential for portable X-ray fluorescence determination of soil copper at ancient metallurgy sites, and considerations beyond measurements of total concentrations.

Copper (Cu) at ancient metallurgy sites represents the earliest instance of anthropogenically generated metal pollution. Such sites are spread across a wide range of environments from Eurasia to South America, and provide a unique opportunity to investigate the past and present extent and impact of metalworking contamination. Establishing the concentration and extent of soil Cu at archaeometallurgy sites can enhance archaeological interpretations of site use but can also, more fundamentally, provide an initial indication of contamination risk from such sites. Systematic evaluations of total soil Cu concentrations at ancient metalworking sites have not been conducted, due in part to the limitations of conventional laboratory-based protocols. In this paper, we first review what is known about Cu soil concentrations at ancient metallurgy sites. We then assess the benefits and challenges of portable X-ray fluorescence spectrometry (pXRF) as an alternative, rapid technique for the assessment of background and contaminant levels of Cu in soils. We conclude that pXRF is an effective tool for identifying potential contamination. Finally, we provide an overview of some major considerations beyond total Cu concentrations, such as bioavailability assessments, that will need to be considered at such sites to move toward a complete assessment of environmental and human risk.

Febrile neutropenia and refeeding syndrome.

We describe the management of a 4-year-old child with acute lymphoblastic leukaemia (ALL) who presented with febrile neutropenia, Cryptosporidium and subsequently developed refeeding syndrome. Febrile neutropenia is common and can be life-threatening and we highlight the identification of well low-risk neutropenic children with resolved febrile illnesses suitable for early discharge. We also discuss the potential management strategies for Cryptosporidium Refeeding syndrome is not common, but should be considered as a cause of acute inpatient deterioration and is a significant risk, with potential morbidity, in children who have undergone a period of catabolism. This article reviews the current literature and provides useful guidance on these issues.

Developing best-practice Bayesian Belief Networks in ecological risk assessments for freshwater and estuarine ecosystems: a quantitative review.

Bayesian Belief Networks (BBNs) are being increasingly used to develop a range of predictive models and risk assessments for ecological systems. Ecological BBNs can be applied to complex catchment and water quality issues, integrating multiple spatial and temporal variables within social, economic and environmental decision making processes. This paper reviews the essential components required for ecologists to design a best-practice predictive BBN in an ecological risk assessment (ERA) framework for aquatic ecosystems, outlining: (1) how to create a BBN for an aquatic ERA?; (2) what are the challenges for aquatic ecologists in adopting the best-practice applications of BBNs to ERAs?; and (3) how can BBNs in ERAs influence the science/management interface into the future? The aims of this paper are achieved using three approaches. The first is to demonstrate the best-practice development of BBNs in aquatic sciences using a simple nutrient model. The second is to discuss the limitations and challenges aquatic ecologists encounter when applying BBNs to ERAs. The third is to provide a framework for integrating best-practice BBNs into ERAs and the management of aquatic ecosystems. A quantitative review of the application and development of BBNs in aquatic science from 2002 to 2014 was conducted to identify areas where continued best-practice development is required. We outline a best-practice framework for the integration of BBNs into ERAs and study of complex aquatic systems.

Risk factors for sporadic domestically acquired Salmonella serovar Enteritidis infections: a case-control study in Ontario, Canada, 2011.

In Ontario, Canada, the number of Salmonella Enteritidis (SE) cases increased over the years 2005-2010. A population-based case-control study was undertaken from January to August 2011 for the purpose of identifying risk factors for acquiring illness due to SE within Ontario. A total of 199 cases and 241 controls were enrolled. After adjustment for confounders, consuming any poultry meat [adjusted odds ratio (aOR) 2·24, 95% confidence interval (CI) 1·31-3·83], processed chicken (aOR 3·32, 95% CI 1·26-8·76) and not washing hands following handling of raw eggs (OR 2·82, 95% CI 1·48-5·37) were significantly associated with SE infection. The population attributable fraction was 46% for any poultry meat consumption and 10% for processed chicken. Poultry meat continues to be identified as a risk factor for SE illness. Control of SE at source, as well as proper food handling practices, are required to reduce the number of SE cases.

Building HIA approaches into strategies for green space use: an example from Plymouth's (UK) Stepping Stones to Nature project.

The health and well-being benefits of access to green space are well documented. Research suggests positive findings regardless of social group, however barriers exist that limit access to green space, including proximity, geography and differing social conditions. Current public health policy aims to broaden the range of environmental public health interventions through effective partnership working, providing opportunities to work across agencies to promote the use of green space. Health Impact Assessment (HIA) is a combination of methods and procedures to assess the potential health and well-being impacts of policies, developments and projects. It provides a means by which negative impacts can be mitigated and positive impacts can be enhanced, and has potential application for assessing green space use. This paper describes the application of a HIA approach to a multi-agency project (Stepping Stones to Nature--SS2N) in the UK designed to improve local green spaces and facilitate green space use in areas classified as having high levels of deprivation. The findings suggest that the SS2N project had the potential to provide significant positive benefits in the areas of physical activity, mental and social well-being. Specific findings for one locality identified a range of actions that could be taken to enhance benefits, and mitigate negative factors such as anti-social behaviour. The HIA approach proved to be a valuable process through which impacts of a community development/public health project could be enhanced and negative impacts prevented at an early stage; it illustrates how a HIA approach could enhance multi-agency working to promote health and well-being in communities.

Management of obstetric anal sphincter injuries--a role for the colorectal surgeon.

AIM: To determine if surgical repair of third and fourth degree obstetric perineal tears by an experienced colorectal surgeon produces satisfactory functional results in the short and long term. METHOD: Consecutive deliveries were studied prospectively over a 32-month period. All patients with suspected third or fourth degree tears were referred to the colorectal team. Following confirmation of the injury, patients underwent surgical repair using a standard overlapped technique according to an established protocol. The patients were reviewed 2 months later. Long-term continence was determined, by postal and telephone follow up, after a minimum of 3 years. RESULTS: Fifty-nine sphincter injuries were identified and repaired by the colorectal team. Two months following repair 51 (86%) of patients had normal continence, four (7%) had urgency, and five (8%) had occasional incontinence of flatus. All patients with any degree of incontinence underwent endoanal ultrasound at which no sphincter defects were noted, and all improved symptomatically following pelvic floor physiotherapy. Long-term follow up data was obtained in 45 women. Thirty-nine (87%) had normal continence scores, 11 (24%) described urgency, but only three (7%) were often incontinent of liquid stool. Seven (15%) were occasionally incontinent of flatus. CONCLUSION: Excellent short and long-term functional results were obtained in the repair of third and fourth degree tears when performed by experienced colorectal surgeons. Since the protocol was established, obstetricians in North Cheshire have adopted the double overlapped technique, and now manage the majority of these injuries themselves.

Elemental formula associated hypophosphataemic rickets.

OBJECTIVES: Hypophosphataemic rickets (HR) is usually secondary to renal phosphate wasting but may occur secondary to reduced intake or absorption of phosphate. We describe a series of cases of HR associated with the use of Neocate®, an amino-acid based formula (AAF). METHODS: A retrospective review of cases with HR associated with AAF use presenting to centres across the United Kingdom. RESULTS: 10 cases were identified, over a 9 month period, all associated with Neocate® use. The age at presentation was 5 months to 3 years. The majority (8/10) were born prematurely. Gastro oesophageal reflux disease (6/10) was the most frequent indication for AAF use. Radiologically apparent rickets was observed after a median of 8 months (range 3-15 months) of exclusive Neocate® feed. The majority (7/10) were diagnosed on the basis of incidental findings on radiographs: rickets (6/10) or fracture with osteopenia (5/10). All patients had typical biochemical features of HR with low serum phosphate, high alkaline phosphatase, normal serum calcium and 25 hydroxyvitamin D. However, in all cases the tubular reabsorption of phosphate (TRP) was ≥96%. Phosphate supplementation resulted in normalisation of serum phosphate within 1-16 weeks, and levels remained normal only after Neocate® cessation. In patients with sufficient follow up duration (4/10), normalisation of phosphate and radiological healing of rickets was noted after 6 months (range: 6-8 months) following discontinuation of Neocate®. CONCLUSION: The presence of a normal TRP and resolution of hypophosphataemia and rickets following discontinuation of Neocate® indicates this is a reversible cause likely mediated by poor phosphate absorption. Close biochemical surveillance is recommended for children on Neocate®, especially in those with gastrointestinal co-morbidities, with consideration of a change in feed or phosphate supplementation in affected children.

Georeferenced soil provenancing with digital signatures.

The provenance or origin of a soil sample is of interest in soil forensics, archaeology, and biosecurity. In all of these fields, highly specialized and often expensive analysis is usually combined with expert interpretation to estimate sample origin. In this proof of concept study we apply rapid and non-destructive spectral analysis to the question of direct soil provenancing. This approach is based on one of the underlying tenets of soil science - that soil pedogenesis is spatially unique, and thus digital spectral signatures of soil can be related directly, rather than via individual soil properties, to a georeferenced location. We examine three different multivariate regression techniques to predict GPS coordinates in two nested datasets. With a minimum of data processing, we show that in most instances Eastings and Northings can be predicted to within 20% of the range of each within the dataset using the spectral signatures produced via portable x-ray fluorescence. We also generate 50 and 95% confidence intervals of prediction and express these as a range of GPS coordinates. This approach has promise for future application in soil and environmental provenancing.

Practical management of functional abdominal pain in children.

Functional abdominal pain (FAP) is common in childhood, but is not often caused by disease. It is often the impact of the pain rather than the pain itself that results in referral to the clinician. In this review, we will summarise the currently available evidence and discuss the functional dimensions of the presentation, within the framework of commonly expressed parental questions. Using the Rome III criteria, we discuss how to classify the functional symptoms, investigate appropriately, provide reassurance regarding parental worries of chronic disease. We outline how to explain the functional symptoms to parents and an individualised strategy to help restore function.

Physical soil architectural traits are functionally linked to carbon decomposition and bacterial diversity.

Aggregates play a key role in protecting soil organic carbon (SOC) from microbial decomposition. The objectives of this study were to investigate the influence of pore geometry on the organic carbon decomposition rate and bacterial diversity in both macro- (250-2000 µm) and micro-aggregates (53-250 µm) using field samples. Four sites of contrasting land use on Alfisols (i.e. native pasture, crop/pasture rotation, woodland) were investigated. 3D Pore geometry of the micro-aggregates and macro-aggregates were examined by X-ray computed tomography (µCT). The occluded particulate organic carbon (oPOC) of aggregates was measured by size and density fractionation methods. Micro-aggregates had 54% less µCT observed porosity but 64% more oPOC compared with macro-aggregates. In addition, the pore connectivity in micro-aggregates was lower than macro-aggregates. Despite both lower µCT observed porosity and pore connectivity in micro-aggregates, the organic carbon decomposition rate constant (Ksoc) was similar in both aggregate size ranges. Structural equation modelling showed a strong positive relationship of the concentration of oPOC with bacterial diversity in aggregates. We use these findings to propose a conceptual model that illustrates the dynamic links between substrate, bacterial diversity, and pore geometry that suggests a structural explanation for differences in bacterial diversity across aggregate sizes.

Pharmacokinetic study of single doses of oral fludarabine phosphate in patients with "low-grade" non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia.

PURPOSE: Fludarabine phosphate (F-AMP), a purine analog, requires daily intravenous administration. A pharmacokinetic study of an oral formulation (10 mg immediate-release tablet) was undertaken in patients with "low-grade" non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia. PATIENTS AND METHODS: Oral F-AMP was incorporated into the "conventional" treatment schedule. Single oral trial doses of 50, 70, and 90 mg of F-AMP were given on the first day of three cycles of treatment; a comparative 50-mg intravenous trial dose was given on the first day of the fourth cycle. Intravenous F-AMP (25 mg/m2) was given on days 2 to 5 at 4-week intervals. Pharmacokinetic samples taken after each trial dose were analyzed for plasma 2-fluoro-arabinofuranosyladenine (2F-ara-A) concentration (its main metabolite); area under the curve 0 to 24 hours (AUC(0-24h)) and maximum concentration (Cmax) were calculated. Eighteen patients received all three oral trial doses, and bioavailability was determined in 15 patients who completed four courses of therapy. RESULTS: Oral administration of F-AMP resulted in a dose-dependent increase in Cmax and AUC(0-24h) of 2F-ara-A and achieved an AUC(0-24h) similar to intravenous administration, although at a lower Cm. The linear increase in mean AUC(0-24h) by factors of 1.36 +/- 0.22 (mean +/- SD) and 1.72 +/- 0.31 corresponded well with the increase in oral dose from 50 to 70 mg (factor of 1.4) and 90 mg (factor of 1.8), respectively. Bioavailability (approximately 55%, with low intraindividual variation) and time to Cmax were dose independent. CONCLUSION: Oral doses of F-AMP can achieve an AUC(0-24h) of 2F-ara-A similar to intravenous administration, with dose-independent bioavailability. The tablet will greatly enhance the use of F-AMP in a palliative setting.

Soil, water, and pasture enrichment of antimony and arsenic within a coastal floodplain system.

Moderate levels of enrichment with environmental contaminants, such as arsenic (As) and antimony (Sb), have received less attention than gross contamination related to obvious point sources of pollution. Within the Macleay floodplain of north-eastern NSW it was found that approximately 90% of the floodplain is enriched in As and Sb, and 6-8% of the floodplain contains As and Sb levels greater than current Australian soil environmental investigation levels. Variation in surface and depth distributions indicated flood deposition of As and Sb across major environmental floodplain environments, with highest accumulation in modern swamp depositional environments. The soil enrichment was reflected by pasture uptake (up to 6.4 and 2.2 mg kg(-1) for As and Sb, respectively) and elevated surface water concentrations (up to 10 and 21 times drinking guideline values and 2.9 and 6.9 times freshwater trigger values for protection of 95% of species for As and Sb, respectively) of these metalloids. Significant relationships between pasture and total soil levels imply higher relative availability than is typical at grossly contaminated sites. Implications for metalloid mobility and availability in acid sulfate soil environments in the floodplain are discussed.

Endoscopy waiting times and impact of the two week wait scheme on diagnosis and outcome of upper gastrointestinal cancer.

The NHS has introduced the two week wait scheme to detect upper gastrointestinal cancers at an early stage and improve survival rates The aim of this study was to assess the impact of this scheme and changes in endoscopy waiting times on tumour stage and resection rates over a four year period. Data were analysed prospectively for all patients diagnosed with oesophagogastric cancer between September 1998 and September 2002 and from those referred under the two week wait scheme since its introduction in 2000. Of those tumours diagnosed by this scheme (15%) only 5% were early disease (stage 1 or 2). Patients with early cancer, mainly diagnosed by routine gastroscopy, do not present with symptoms meeting the two week wait criteria. An increase in the resection rates for early disease will most probably be seen with a reduction in routine endoscopy waiting times.

Lymphotoxin beta receptor signaling limits mucosal damage through driving IL-23 production by epithelial cells.

The immune mechanisms regulating epithelial cell repair after injury remain poorly defined. We demonstrate here that lymphotoxin beta receptor (LTßR) signaling in intestinal epithelial cells promotes self-repair after mucosal damage. Using a conditional gene-targeted approach, we demonstrate that LTßR signaling in intestinal epithelial cells is essential for epithelial interleukin-23 (IL-23) production and protection against epithelial injury. We further show that epithelial-derived IL-23 promotes mucosal wound healing by inducing the IL-22-mediated proliferation and survival of epithelial cells and mucus production. Additionally, we identified CD4(-)CCR6(+)T-bet(-) RAR-related orphan receptor gamma t (RORγt)(+) lymphoid tissue inducer cells as the main producers of protective IL-22 after epithelial damage. Thus, our results reveal a novel role for LTßR signaling in epithelial cells in the regulation of intestinal epithelial cell homeostasis to limit mucosal damage.

Sudden withdrawal of carbamazepine increases cardiac sympathetic activity in sleep.

OBJECTIVE: To evaluate the cardiac autonomic effects of abrupt withdrawal of carbamazepine (CBZ) during sleep in patients with epilepsy. BACKGROUND: The pathophysiology of sudden unexpected death in epilepsy (SUDEP) is uncertain, with ictal or peri-ictal cardiorespiratory compromise appearing probable. Risk factors for SUDEP include multiple antiepileptic drugs (AED), poor compliance, and abrupt AED withdrawal. The spectral analysis of the beat-to-beat heart rate variability (HRV) displays two main components: low frequency (LF), representing sympathetic and parasympathetic influence and high frequency (HF), representing parasympathetic influence. The LF/HF ratio is commonly regarded as an indicator of sympathovagal balance. METHOD: Twelve patients with medically intractable seizures underwent abrupt withdrawal of CBZ to facilitate seizure recording during controlled circuit TV-EEG monitoring. Continuous EKG recording was begun 24 hours before CBZ reduction. Spectral analysis of the HRV was performed during selected samples of non-REM sleep before and after CBZ reduction. Analyses were made at least 6 hours after from (complex) partial and 12 hours from generalized seizures. RESULTS: The mean LF/HF ratio before withdrawal of CBZ was 2.15 compared with a ratio of 2.65 on day 4 after withdrawal, an increase of 19% (geometric mean; 95% CI, 2% to 34%; Wilcoxon test, z = 2.36; p = 0.018). The ratio increased in 10 patients compared with a decrease in only one patient. CONCLUSION: Abrupt withdrawal of CBZ leads to enhanced sympathetic activity in sleep as evidenced by increased LF/HF ratios. Increased sympathetic activity in the setting of seizure-induced hypoxia could predispose to SUDEP.

Effects of prazosin and labetalol on blood pressure control and blood lipid levels in patients with mild-to-moderate essential hypertension.

Twenty hypertensive patients entered a crossover, placebo-controlled study of prazosin and labetalol that was designed to compare treatment effects on blood pressure control and lipid parameters. Both drugs significantly reduced sitting and standing systolic and diastolic blood pressures (p less than or equal to 0.01). No significant differences were noted between treatment groups in total cholesterol, high-density lipoprotein cholesterol, or very low-density lipoprotein cholesterol levels. However, a trend toward an increase in low-density lipoprotein cholesterol levels was seen during therapy with labetalol, whereas in contrast, no such effect was seen during treatment with prazosin.

Celiac disease among Ashkenazi Jews from Israel. A study of the HLA class II alleles and their associations with disease susceptibility.

The immunogenetics of celiac disease demonstrates a highly significant association with the HLA class II alleles DQA1*0501 DQB1*0201 encoded in either a cis- or trans-configuration. In Northern Europe, these alleles are found in linkage disequilibrium with DRB1*0301 while in Southern Europe an additional secondary association through linkage disequilibrium is seen with the combination DRB1*1101/0701. This study examines 34 Ashkenazi Jews with celiac disease and 36 ethnically matched controls to determine alleles at the DRB, DQA1, DQB1, and DPB1 loci using SSO probes in conjunction with gene amplification by the PCR. The results confirm a highly significant association with the DQA1*0501 DQB1*0201 allelic combination (71% celiac vs 8% control individuals; p = 0.00005; chi 2 = 21.4). Of celiac subjects, 29% were negative for the proposed DQ susceptibility alleles, the majority of whom were DRB1*0402 positive (20% overall celiac group). No additional susceptibility was associated at the DRB3 and DPB loci. This study confirms that the MHC-linked celiac disease susceptibility among Ashkenazi Jews is closely associated with the presence of the combination of alleles DQA1*0501 DQB1*0201. However, within this population of relatively high-prevalence celiac disease, 30% of celiac patients do not carry these alleles and are therefore not covered by a single "unifying" hypothesis.

Associations between alleles of the major histocompatibility complex-encoded ABC transporter gene TAP2, HLA class II alleles, and celiac disease susceptibility.

The study of celiac disease among Southern European populations has confirmed the hypothesis from Northern Europe that a close association exists between disease susceptibility and a combination of polymorphic alleles at the HLA-DQ loci (DQA1*0501-DQB1*0201) arranged either in a cis- or a trans-configuration. Attempts to identify additional genetic influences have been inconclusive, although many studies have raised possibilities of further major histocompatibility complex (MHC)-linked susceptibility genes. This study examines the disease associations of polymorphisms of a recently discovered gene located close to the DQ loci, TAP2, whose products are thought to be involved in the transport of antigen peptides across the endoplasmic reticulum for binding to HLA class I molecules. Like the products of the DQ loci, the product of TAP2 forms part of a heterodimeric molecule with products of a second genetic locus, TAP1, which is located centromerically to TAP2. The populations studied were central Italians from Rome and Ashkenazi Jews from Rehovot, Israel. HLA studies demonstrate that the Roman celiac group has a high proportion of people with DR3-negative celiac disease in whom the combination DR5/7 is frequently found. In Israel, 20% of celiac patients lack the DQ susceptibility markers but are DR4 positive. The polymorphic substitutions of TAP2 studied encode amino acid changes in the trans-membrane region (position 379) and the ATP-binding cassette region (positions 565 and 665) of the protein. No TAP2-specific disease associations were found in any HLA subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid onset retinopathy in a diabetic patient following bone marrow transplantation.

We report a 38-year-old man who presented in 1998 with advanced multiple myeloma and newly diagnosed diabetes mellitus (DM). Subsequent BMT has been successful after conditioning with melphalan and total body irradiation, but significant ischaemic retinopathy has developed. Chemotherapeutic agents, total body irradiation, and DM are likely to have been co-factors in precipitating the rapid onset of retinopathy. Routine ophthalmic surveillance is recommended for all patients after BMT, particularly for those with additional risk factors for the development of retinopathy such as DM.