Use of gender distribution in routine surveillance data to detect potential transmission of gastrointestinal infections among men who have sex with men in England.

Detecting gastrointestinal (GI) infection transmission among men who have sex with men (MSM) in England is complicated by a lack of routine sexual behavioural data. We investigated whether gender distributions might generate signals for increased transmission of GI pathogens among MSM. We examined the percentage male of laboratory-confirmed patient-episodes for patients with no known travel history for 10 GI infections of public health interest in England between 2003 and 2013, stratified by age and region. An adult male excess was observed for Shigella spp. (annual maximum 71% male); most pronounced for those aged 25-49 years and living in London, Brighton and Manchester. An adult male excess was observed every year for Entamoeba histolytica (range 59.8-76.1% male), Giardia (53.1-57.6%) and Campylobacter (52.1-53.5%) and for a minority of years for hepatitis A (max. 69.8%) and typhoidal salmonella (max. 65.7%). This approach generated a signal for excess male episodes for six GI pathogens, including a characterised outbreak of Shigella among MSM. Stratified analyses by geography and age group were consistent with MSM transmission for Shigella. Optimisation and routine application of this technique by public health authorities elsewhere might help identify potential GI infection outbreaks due to sexual transmission among MSM, for further investigation.

The impact of new national guidance for the public health management of enteric fever in England.

OBJECTIVES: New guidance was published in England in February 2012 to support the public health management of enteric fever and reduce the risks of secondary transmission. The new guidance was evaluated to assess: STUDY DESIGN: Quantitative and qualitative evaluation of the implementation of new public health guidance. METHODS: A qualitative review of all non-travel-related cases from February 2010 to January 2014 to compare the risk of secondary transmission before and after the guidance introduction; an audit of clearance sampling for each case and their contacts reported in London from February 2012-January 2015 to compare with a previous London audit; and an online user survey in November 2014. RESULTS: The proportions of non-travel cases reported before and after the introduction of the new guidance were similar, 6% in 2010-2012 compared to 7% in 2012-2014 (P = 0.33). There was a 32% reduction in the number of clearance samples required for cases and the estimated period of exclusion from work or school was reduced from 54 days to 16 days. Compliance in case clearance improved from 53% to 90% and contact screening compliance improved from 42% to 80%. The targeted screening of contacts led to a significantly higher positive yield (3.6% from 1.5%, P = 0.003). All symptomatic co-travellers presented to a healthcare professional, suggesting that screening could be restricted to those in risk groups for transmission. Feedback from users highlighted additional areas, such as management of large organised groups of co-travellers and those diagnosed abroad, which has informed the update of the national guidance. CONCLUSIONS: The new guidance has not led to an increase in secondary transmission of enteric fever in England and findings have been used to inform an update of the guidance. The new guidance also represents a reduced burden of investigation and thus a likely reduced cost to patients, healthcare professionals, laboratories and environmental health officers.

Thermal scanning probe lithography for the directed self-assembly of block copolymers.

Thermal scanning probe lithography (t-SPL) is applied to the fabrication of chemical guiding patterns for directed self-assembly (DSA) of block copolymers (BCP). The two key steps of the overall process are the accurate patterning of a poly(phthalaldehyde) resist layer of only 3.5 nm thickness, and the subsequent oxygen-plasma functionalization of an underlying neutral poly(styrene-random-methyl methacrylate) brush layer. We demonstrate that this method allows one to obtain aligned line/space patterns of poly(styrene-block-methyl methacrylate) BCP of 18.5 and 11.7 nm half-pitch. Defect-free alignment has been demonstrated over areas of tens of square micrometres. The main advantages of t-SPL are the absence of proximity effects, which enables the realization of patterns with 10 nm resolution, and its compatibility with standard DSA methods. In the brush activation step by oxygen-plasma exposure, we observe swelling of the brush. This effect is discussed in terms of the chemical reactions occurring in the exposed areas. Our results show that t-SPL can be a suitable method for research activities in the field of DSA, in particular for low-pitch, high-χ BCP to achieve sub-10 nm line/space patterns.

The North Wyke Farm Platform: effect of temperate grassland farming systems on soil moisture contents, runoff and associated water quality dynamics.

The North Wyke Farm Platform was established as a United Kingdom national capability for collaborative research, training and knowledge exchange in agro-environmental sciences. Its remit is to research agricultural productivity and ecosystem responses to different management practices for beef and sheep production in lowland grasslands. A system based on permanent pasture was implemented on three 21-ha farmlets to obtain baseline data on hydrology, nutrient cycling and productivity for 2 years. Since then two farmlets have been modified by either (i) planned reseeding with grasses that have been bred for enhanced sugar content or deep-rooting traits or (ii) sowing grass and legume mixtures to reduce nitrogen fertilizer inputs. The quantities of nutrients that enter, cycle within and leave the farmlets were evaluated with data recorded from sensor technologies coupled with more traditional field study methods. We demonstrate the potential of the farm platform approach with a case study in which we investigate the effects of the weather, field topography and farm management activity on surface runoff and associated pollutant or nutrient loss from soil. We have the opportunity to do a full nutrient cycling analysis, taking account of nutrient transformations in soil, and flows to water and losses to air. The NWFP monitoring system is unique in both scale and scope for a managed land-based capability that brings together several technologies that allow the effect of temperate grassland farming systems on soil moisture levels, runoff and associated water quality dynamics to be studied in detail. HIGHLIGHTS: Can meat production systems be developed that are productive yet minimize losses to the environment?The data are from an intensively instrumented capability, which is globally unique and topical.We use sensing technologies and surveys to show the effect of pasture renewal on nutrient losses.Platforms provide evidence of the effect of meteorology, topography and farm activity on nutrient loss.

An unusual case of bilateral pyoderma gangrenosum with Achilles tendon rupture.

Pyoderma gangrenosum (PG) is a rare, noninfectious, inflammatory disease characterized by neutrophilic infiltration of the dermis and destruction of tissue. PG is a diagnostic challenge, which can lead to late diagnosis, delayed treatment and detrimental surgical interventions. We describe a presentation not previously reported, affecting deep muscle and tendon leading to tendon rupture. Furthermore, we show the multidisciplinary team approach to management of a patient with PG and the reconstructive surgical element. A 31-year-old woman presented with a rapid onset painful, tender, left calf and ankle, which was associated with a mild flare of ulcerative colitis. Investigations revealed a white cell count of 26 × 10(9) cells L(-1) , a C-reactive protein count of 226 mg L(-1) , no deep vein thrombosis on ultrasound, no bone or joint involvement on X-ray and no organisms on joint aspirate. Debridement was undertaken after the left ankle developed a foul-smelling discharging wound. Repeat debridement led to worsening of the condition (pathergy). Intraoperative tissue cultures and microscopy showed no evidence of fungi, bacteria or mycobacteria. Histology showed granulation, inflammatory infiltrate, abscess formation and focal necrotizing vasculitis. Dermatology opinion confirmed PG. Awareness of the diagnosis of PG, and early involvement of dermatology, in a rapidly progressing wound is essential to avoid delayed treatment and prevent worsening through pathergy.

Multi Tbit/in(2) storage densities with thermomechanical probes.

Exploiting the spatial resolution of scanning probes presents an attractive approach for novel data storage technologies in particular for large-scale data repositories because of their inherent potential for high storage density. We show that multi-Tbit/in(2) density can be achieved by means of thermomechanically embossing the information as indentation marks into a polymer film. The data density is determined by the nonlinear interaction between closely spaced indents and the fundamental scaling relations governing the shape and size of the indents. We find that cooperative effects in polymers give rise to a minimum indentation radius on the order of the correlation length of the cooperatively rearranged region even if formed by an infinitely sharp indenter. Thus, cooperativity coupled to alpha-transitions in polymers is evinced in a real space geometrical experiment. Furthermore, we predict that indentation marks cannot be made smaller than 5 nm in diameter, which limits the feature resolution for embossing technologies in general.

Macromolecular structure information and databases. The EU BRIDGE Database Project Consortium.

The current status and future outlook of macromolecular structure databases and information handling, with particular reference to European databases, are reviewed. Issues concerning the efficiency with which data are represented, validated, archived and accessed are discussed in view of the fast growing body of information on structures of biological macromolecules.

Computational gene discovery and human disease.

Bioinformatics is now an essential tool in many aspects of human molecular genetics research. Methods for the prediction of gene structure are essential components in genomic sequencing projects and provide the key to deriving protein sequence and locating intron/exon junctions. Sequence comparison and database searching are the pre-eminent approaches for predicting the likely biochemical function of new genes, although sequence profiles derived from families of aligned sequences have advantages in the detection of remote sequence relationships. The use of sequence database analysis for large-scale comparative analysis of genome sequence data from model organisms is emerging as the most important recent development in the application of bioinformatics methods for characterizing candidate disease genes.

Quantitative aspects of the formation and loss of DNA interstrand crosslinks in Chinese hamster cells following treatment with cis-diamminedichloroplatinum(II) (cisplatin). II. Comparison of results from alkaline elution, DNA renaturation and DNA sedimentation studies.

The formation of interstrand crosslinks in the DNA of cis-diamminedichloroplatinum(II) (cisplatin)-treated Chinese hamster cells has been demonstrated by three independent, highly sensitive techniques: namely those of alkaline elution, renaturation of crosslinked DNA and alkaline sucrose gradient velocity sedimentation. Simultaneous measurement of DNA break frequency by the first two methods and a computer model combined with the third enabled the calculation of crosslink frequency after application of low doses of cisplatin. Good agreement was found between the values obtained by the three methods used here, and also with those obtained by direct measurement of the amount of crosslinked hybrid DNA in density-labelled cells treated with higher doses of cis-platin (Roberts, J.J. and Friedlos, F. (1981) Biochim. Biophys, Acta 655, 146--151). When measured by all three methods described here, crosslinking was found to increase during several hours after treatment and then to decrease with a half-life of between 12 and 24 h. For low initial levels of crosslinking, this was largely attributed to an excision repair process, since the formation of breaks in DNA was only minimal.

Identification and analysis of multigene families by comparison of exon fingerprints.

Gene families are often recognised by sequence homology using similarity searching to find relationships, however, genomic sequence data provides gene architectural information not used by conventional search methods. In particular, intron positions and phases are expected to be relatively conserved features, because mis-splicing and reading frame shifts should be selected against. A fast search technique capable of detecting possible weak sequence homologies apparent at the intron/exon level of gene organization is presented for comparing spliceosomal genes and gene fragments. FINEX compares strings of exons delimited by intron/exon boundary positions and intron phases (exon fingerprint) using a global dynamic programming algorithm with a combined intron phase identity and exon size dissimilarity score. Exon fingerprints are typically two orders of magnitude smaller than their nucleic acid sequence counterparts giving rise to fast search times: a ranked search against a library of 6755 fingerprints for a typical three exon fingerprint completes in under 30 seconds on an ordinary workstation, while a worst case largest fingerprint of 52 exons completes in just over one minute. The short "sequence" length of exon fingerprints in comparisons is compensated for by the large exon alphabet compounded of intron phase types and a wide range of exon sizes, the latter contributing the most information to alignments. FINEX performs better in some searches than conventional methods, finding matches with similar exon organization, but low sequence homology. A search using a human serum albumin finds all members of the multigene family in the FINEX database at the top of the search ranking, despite very low amino acid percentage identities between family members. The method should complement conventional sequence searching and alignment techniques, offering a means of identifying otherwise hard to detect homologies where genomic data are available.

Are grammatical representations useful for learning from biological sequence data?--a case study.

This paper investigates whether Chomsky-like grammar representations are useful for learning cost-effective, comprehensible predictors of members of biological sequence families. The Inductive Logic Programming (ILP) Bayesian approach to learning from positive examples is used to generate a grammar for recognising a class of proteins known as human neuropeptide precursors (NPPs). Collectively, five of the co-authors of this paper, have extensive expertise on NPPs and general bioinformatics methods. Their motivation for generating a NPP grammar was that none of the existing bioinformatics methods could provide sufficient cost-savings during the search for new NPPs. Prior to this project experienced specialists at SmithKline Beecham had tried for many months to hand-code such a grammar but without success. Our best predictor makes the search for novel NPPs more than 100 times more efficient than randomly selecting proteins for synthesis and testing them for biological activity. As far as these authors are aware, this is both the first biological grammar learnt using ILP and the first real-world scientific application of the ILP Bayesian approach to learning from positive examples. A group of features is derived from this grammar. Other groups of features of NPPs are derived using other learning strategies. Amalgams of these groups are formed. A recognition model is generated for each amalgam using C4.5 and C4.5rules and its performance is measured using both predictive accuracy and a new cost function, Relative Advantage (RA). The highest RA was achieved by a model which includes grammar-derived features. This RA is significantly higher than the best RA achieved without the use of the grammar-derived features. Predictive accuracy is not a good measure of performance for this domain because it does not discriminate well between NPP recognition models: despite covering varying numbers of (the rare) positives, all the models are awarded a similar (high) score by predictive accuracy because they all exclude most of the abundant negatives.

Neurologic, psychiatric, and cardiovascular complications in children struck by lightning.

The neurologic changes following lightning injury include coma with cerebral edema, inappropriate secretion of antidiuretic hormone (ADH), seizures, cerebellar ataxia, and painful sensory disturbances. Deteriorating neurologic status may warrant the use of intracranial pressure monitoring devices. Myocardial injury and transient hypertension are generally evident at the onset. Monitoring of the cardiac rhythm may be needed for as long as a week for late onset arrythmia. Abnormalities of memory, mood, and affect noted on recovery of consciousness may persist for months, necessitating close psychiatric and neurlologic follow-up.

Effect of long-term aspirin treatment on platelet adhesion to chronically damaged canine pulmonary arteries.

The effect of aspirin on platelet adhesion to chronically damaged pulmonary arteries was studied in 18 dogs. Chronic injury was produced in all dogs by infection with the canine heartworm Dirofilaria immitis (DI). Ten dogs were subjected to 4 days of chronic injury. Eight dogs were subjected to 30 days of chronic injury. Five of the 4 day injury and 4 of the 30 day injury dogs received aspirin daily; (325 mg/day orally). Aspirin was started 3 days prior to infection with DI. Pulmonary arteries were perfusion fixed in situ at physiologic pressure. The damaged pulmonary arteries were located by Evan's blue staining (2 ml/kg of 1% dye given one hr prior to perfusion) and prepared for scanning electron microscopy. Both groups of dogs with 4 day DI infection had monolayers of platelets adhered to exposed subendothelium. Aspirin treated dogs had enhanced platelet adhesion to damaged arteries. Aspirin treatment for 33 days reduced platelet adhesion. The damaged arteries of treated dogs infected with DI for 30 days had very few platelets adhering to the damaged surface. However, non-treated dogs subjected to 30 days of infection had platelet adhesion equivalent to the 4 day non-treated infection group. These results suggest that although aspirin is ineffective in preventing platelet adhesion in short term therapy it is effective when given for longer time periods. This inhibitory effect may occur due to platelet membrane changes rather than because of aspirin inhibition of cyclooxygenase.

Smooth muscle proliferation in chronically injured canine pulmonary arteries is reduced by a potent platelet aggregation inhibitor U-53,059.

Dirofilaria immitis (DI) infection chronically injures canine pulmonary arteries. This injury produces endothelial cell loss, platelet/leukocyte adhesion, and smooth muscle proliferation. In the present study we assessed the effect of the cyclooxygenase inhibitor, U-53,059, on platelet function, platelet kinetics, coagulation, and smooth muscle proliferation in DI infected dogs. Platelet aggregation to the combination of arachidonic acid/ADP was significantly inhibited by U-53,059. Coagulation and hematologic parameters were not effected by either DI infection or U-53,059 treatment. Platelet survival and the number of platelet dense granules were reduced in DI infection. Quantification of the lesions demonstrated that U-53,059 reduced both severity and density compared to non-treated dogs. U-53,059 is a potent and effective inhibitor of platelet aggregation which modifies smooth muscle proliferation produced by chronic vascular injury.

A randomised trial of patient repositioning during radiotherapy using a megavoltage imaging system.

Effectiveness of radiotherapy is dependent on the accuracy of beam alignment. Recent developments in megavoltage imaging allow real-time monitoring of beam placement. Maximum gains from this new technology can only be made if the information is utilised to correct patient positioning prospectively before the majority of a treatment fraction is delivered. We have developed and utilised an integrated megavoltage imaging system to perform a randomised trial demonstrating significant improvements in accuracy using treatment intervention techniques for pelvic radiotherapy. The mean field-placement accuracy improved from 4.3 mm to 2 mm and the proportion of treatments given with a field-placement error of > or = 5 mm decreased from 69% to 7%. This improvement in accuracy may enable smaller margins around the target volume to be chosen whilst ensuring complete target coverage at each treatment fraction.

Prolonged perfusion with a membrane oxygenator in awake ponies.

Prolonged extracorporeal membrane oxygenation (PEMO) was performed in 6 adult ponies with the membrane oxygenator in vein-to-artery bypass circuit. A flow rate equal to 46 per cent of control cardiac output was diverted through the PEMO circuit of 10 to 24 hours. Three of the 6 ponies were perfused for at least 20 hours and developed no complications. Immediately following initiation of PEMO, left ventricular output decreased; however, in the interval between 6 and 24 hours, left ventricular output was increased above control levels. Aortic pressure and left ventricular work were markedly elevated during PEMO. Pulmonary ventilation and oxygen uptake also decreased initially but were elevated during later stages of bypass. Pulmonary compliance did not change, except in those studies in which problems were encountered with perfusion techniques. Hepatic glycolysis and hyperglycemia occurred and were more severe in ponies with catheter-produced thrombi. Marked diuresis, which could be attributed only partially to the hyperglycemia, was present throughout PEMO. Based on the minimal morphologic changes observed in the ponies, extracorporeal circulation diverting one half of the cardiac output through a membrane oxygenator can be safely performed for up to 24 hours.

Development of a molecular probe to baboon interleukin-10 mRNA for in situ hybridization during experimental schistosomiasis.

A nucleic acid probe complementary to baboon interleukin 10 (IL-10) mRNA was developed for in situ hybridization. Highly conserved IL-10 protein sequences from several mammals were aligned to design oligonucleotide primers flanking a 270-bp sequence of the target cDNA. RNA was isolated from stimulated peripheral blood mononuclear cells (PBMC). IL-10 cDNA was reverse-transcribed from the total PBMC RNA and amplified with the polymerase chain reaction (PCR). Cloning and sequencing of the PCR product confirmed it to be of baboon IL-10 origin, with 97.8% identity to human and 100% identity to macaque mRNA sequences. The baboon IL-10 DNA probe hybridized in Southern blots to a 7.9-Kbp or 8.6-Kbp band after digestion of genomic baboon DNA with Bam H1 or Eco R1, respectively. Preliminary results with an antisense riboprobe derived from this sequence showed the presence of IL-10 mRNA in sections of granulomatous tissues.

Solitary eosinophilic granuloma of the skull.

Solitary eosinophilic granuloma of the skull is a rare lesion, the natural history of which has not been defined completely. By a retrospective chart review, 26 patients were identified as having a solitary eosinophilic granuloma of the skull at first presentation to our institution between 1946 and 1982. Characteristically, the patient noted an enlarging, tender skull mass during the several weeks to several months before the initial assessment. Laboratory findings were normal except for 1 case of eosinophilia. Radiographically, the abnormality consisted of a punched-out, well defined, lytic lesion most commonly seen in the parietal or frontal bone. Whole body bone scans or bone surveys were used to rule out further lesions. The definitive diagnosis was made by histological examination, which showed the characteristic histiocytes, eosinophils, and multinucleated cells of eosinophilic granuloma. The usual treatment consisted of a craniectomy or curettage perhaps followed by local, moderate dose radiation therapy. The follow-up period ranged from 1 month to 25 years and averaged 8 years; in that time, 8 patients (31%) developed additional lesions. Of these 8 patients, only 3 were older than 3 years at the time of the first recurrence. Based on a review of our own patients and those reported in the literature, we stress that a solitary eosinophilic granuloma of the skull may foreshadow future disease elsewhere and is not an easily dimissed local disease, especially in children. After the initial treatment, we recommend careful long term follow-up and treatment of additional lesions with radiation therapy.

Aspergillus disc space infection: case report and review of the literature.

Aspergillus disc space infection is an unusual complication of the immunocompromised state. Magnetic resonance imaging may aid the clinician in arriving at a prompt diagnosis of discitis in affected patients. We report a case of systemically acquired Aspergillus discitis at multiple levels diagnosed by plain x-ray films, bone scan, magnetic resonance imaging, and biopsy. We review the literature on this subject and suggest that aggressive diagnosis with early biopsy, treatment with systemic antifungal agents, and surgical debridement of the infected disc space yield the best outcome for these patients.

Syringomyelia in a man with sarcoidosis.

Sarcoidosis, generally a systemic ailment, uncommonly affects the central nervous system. It only rarely affects the spinal cord alone or in combination with other areas. Syringomyelia has never been associated with sarcoidosis. We report the case of a 32-year-old man with sarcoidosis who presented with surgically verified syringomyelia. The pertinent literature is reviewed. The mechanisms by which sarcoidosis could cause a syrinx are discussed.