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Neurothekeoma, a lesion of possible fibrohistiocytic origin, is a rare, benign, superficial soft tissue tumor, histologically subclassified in 3 types: myxoid, cellular, or mixed. It clinically presents as a solitary, pink to brown nodule, ranging from 0.3 to 2.0 cm. Four point mutations (PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M) were identified by next-generation sequencing of a neurothekeoma presenting in the left inner thigh of a 53-year-old man. We highlight novel genetic alterations (SMO G461S and ERBB3 L77M) and previously known mutations (PI3KCA w552* and ALK P1469S) that play a role in other pathogenic pathways, but to the best of our knowledge, these have not yet been reported in neurothekeoma.

Basal cell carcinoma (BCC) is the most commonly diagnosed cutaneous cancer in the United States with more than 2.5 million treated annually. Genetic studies have revealed that approximately 90% of BCCs have a mutation in the hedgehog-signaling pathway. Patients with BCC usually have an excellent prognosis with surgical modalities, however, patients with locally advanced BCC may potentially experience significant cosmetic or functional impairment, with only surgical intervention. Vismodegib is a hedgehog pathway inhibitor that has been successful in treating patients with locally advanced BCC. We report a patient with BCC with a good response to vismodegib and a novel xanthomatous change in the excision specimen.

Graphical abstract, Highlights • Unusual genotypes (G1 non 1a/1b or G4 non 4a/4d) were common in African patients. • 11 previously unclassified HCV subtypes were represented including novel G1p. • Patients with unusual G1 subtypes had a lower SVR rate than any other genotype. • Failures were driven by patients treated with a first generation NS5A inhibitor. • The majority of unusual G1 subtypes had baseline NS5A resistance mutations., Background & Aims HCV subtypes which are unusual in Europe are more prevalent in the African region, but little is known of their response to direct-acting antivirals (DAAs). These include non-1a/1b/ non-subtypeable genotype 1 (G1) or non-4a/4d (G4). In this report we aimed to describe the genotype distribution and treatment outcome in a south London cohort of African patients. Methods We identified all patients born in Africa who attended our clinic from 2010-2018. Information on HCV genotype, treatment regimen and outcome were obtained. Non-subtypeable samples were analysed using Glasgow NimbleGen next-generation sequencing (NGS). Phylogenetic analysis was carried out by generating an uncorrected nucleotide p-distance tree from the complete coding regions of our sequences. Results Of 91 African patients, 47 (52%) were infected with an unusual subtype. Fourteen novel, as yet undesignated subtypes (G1*), were identified by NGS. Three individuals were infected with the same subtype, now designated as subtype 1p. Baseline sequences were available for 22 patients; 18/22 (82%) had baseline NS5A resistance-associated substitutions (RASs). Sustained virological response (SVR) was achieved in 56/63 (89%) overall, yet only in 21/28 (75%) of those with unusual G1 subtypes, with failure in 3/16 G1*, 1/2 G1p and 3/3 in G1l. Six treatment failures occurred with sofosbuvir/ledipasvir compared to 1 failure on a PI-based regimen. The SVR rate for all other genotypes and subtypes was 35/35 (100%). Conclusions Most individuals in an unselected cohort of African patients were infected with an unusual genotype, including novel subtype 1p. The SVR rate of those with unusual G1 subtypes was 75%, raising concern about expansion of DAAs across Africa. Depending on the regimen used, higher failure rates in African cohorts could jeopardise HCV elimination. Lay summary Direct-acting antiviral medications are able to cure hepatitis C in the majority of patients. The most common genotype of hepatitis C in Europe and the United States is genotype 1a or 1b and most clinical trials focused on these genotypes. We report that in a group of African patients, most of them had unusual (non-1a/1b) genotype 1 subtypes, and that the cure rate in these unusual genotypes was lower than in genotypes 1a and 1b.

Summary Background Transmission of hepatitis C virus (HCV) in the healthcare setting is rare. Routine infection prevention and control measures mean that this should be a preventable ‘never event’. Aim To investigate the diagnosis of acute healthcare-associated HCV infection. Methods Epidemiological and molecular investigation of a case of acute HCV infection associated with nosocomial exposure. Findings Detailed investigation of the treatment history of a patient with acute HCV infection identified transmission from a co-attending patient in an emergency department as the likely source; this possibility was confirmed by virus sequence analysis. The precise route of transmission was not identified, though both patient and source had minimally invasive healthcare interventions. Review of infection, prevention and control identified potentially contributory factors in the causal pathway including hand hygiene, inappropriate use of personal protective equipment, and blood contamination of the surface of the departmental blood gas analyser. Conclusion We provide molecular and epidemiological evidence of HCV transmission between patients in an emergency department that was made possible by environmental contamination. Patients with HCV infection are higher users of emergency care than the general population and a significant proportion of those affected remain unknown and/or infectious. Equipment, departmental design, staff behaviour, and patient risk require regular review to minimize the risk of nosocomial HCV transmission.

To have epidemic potential, a pathogen must be able to spread in human populations, but of human-infective RNA viruses only a minority can do so. We investigated the evolution of human transmissibility through parallel analyses of 1755 virus genome sequences from 39 RNA virus genera. We identified 57 lineages containing human-transmissible species and estimated that at least 74% of these lineages have evolved directly from non-human viruses in other mammals or birds, a public health threat recently designated “Disease X”. Human-transmissible viruses rarely evolve from virus lineages that can infect but not transmit between humans. This result cautions against focussing surveillance and mitigation efforts narrowly on currently known human-infective virus lineages and supports calls for a better understanding of RNA virus diversity in non-human hosts.

A multi-element soil geochemical survey was conducted over the conterminous United States from 2007–2010 in which 4,857 sites were sampled representing a density of 1 site per approximately 1,600 km2. Following adjustments for censoring and dropping highly censored elements, a total of 41 elements were retained. A logcentred transform was applied to the data followed by the application of a principal component analysis. Using the 10 most dominant principal components for each layer (surface soil, A-horizon, C-horizon) the application of random forest classification analysis reveals continental-scale spatial features that reflect bedrock source variability. Classification accuracies range from near zero to greater than 74% for 17 surface lithologies that have been mapped across the conterminous United States. The differences of classification accuracy between the Surface Layer, A- and C-Horizons do not vary significantly. This approach confirms that the soil geochemistry across the conterminous United States retains the characteristics of the underlying geology regardless of the position in the soil profile.

Pigs raised in the United Kingdom are unlikely to be the source of UK human infections., Since 2010, reports of infection with hepatitis E virus (HEV) have increased in England and Wales. Despite mounting evidence regarding the zoonotic potential of porcine HEV, there are limited data on its prevalence in pigs in the United Kingdom. We investigated antibody prevalence, active infection, and virus variation in serum and cecal content samples from 629 pigs at slaughter. Prevalence of antibodies to HEV was 92.8% (584/629), and HEV RNA was detected in 15% of cecal contents (93/629), 3% of plasma samples (22/629), and 2% of both (14/629). However, although HEV is prevalent in pigs in the United Kingdom and viremic pigs are entering the food chain, most (22/23) viral sequences clustered separately from the dominant type seen in humans. Thus, pigs raised in the United Kingdom are unlikely to be the main source of human HEV infections in the United Kingdom. Further research is needed to identify the source of these infections.

Human polyomavirus-7-associated rash and pruritus (PVARP) is a chronic superficial viral skin infection, which primarily impacts immunocompromised individuals. We report on a case of PVARP in a lung transplant recipient. Our patient developed symptoms 13 years after being on his immunosuppressive regimen, with an insidious course of progressive gray lichenification with marked islands of sparing and quality of life-altering pruritus. Treatment for PVARP is not established; however, topical cidofovir combined with immunomodulation may offer sustained therapeutic benefit.

Background Hepatitis E virus is well recognized cause of acute hepatitis. Traditionally hepatitis E virus (HEV) infections were generally associated with travel to Asia and Africa. Autochthonous hepatitis E is recognized as a major cause acute hepatitis in England and Wales. However, autochthonous hepatitis E has never been documented in Scotland. Objectives We attempted to determine if autochthonous HEV occurred in Scotland. Study design Samples from 377 individuals in the South-East of Scotland presenting with acute hepatitis were tested over six years. Acute hepatitis E was confirmed by detecting viraemia or documenting seroconversion and ORF-2 region sequenced. Structured interviews were carried out to identify risk factors for infection. Results Sixteen individuals (4.2%) had evidence of past HEV infection. Twelve (3.2%) had acute HEV infection, 10 of whom had viraemia (genotype 1 = 3; genotype 3 = 7). Of these seven with genotype 3 infection, three had not travelled outside Scotland within the incubation period, while four had travelled to Spain ( n = 3) or Turkey ( n = 1). All three individuals with genotype 1 infection had travelled to the Indian subcontinent. Conclusions A significant proportion of HEV genotype 3 infections was autochthonous (43%). HEV screening should hence be an integral part of acute hepatitis screening in Scotland, irrespective of the travel history.

A woman developed acute hepatitis C (HCV) infection 2 months after delivering her baby at a London Hospital. The other patients who had been on the unit at the same time all had negative HCV serology antenatally. Testing of the healthcare workers who had been involved in this patient's care revealed that one of the midwives who only worked on the postnatal unit was chronically infected with the same viral genotype. Sequencing and phylogenetic analysis revealed close identity between the viruses from the two individuals. Although, the midwife had only performed non-exposure prone procedures including venepuncture and cannulation, our findings indicate that transmission of the virus had occurred from the healthcare worker to the patient. The potential implications of this case within the setting of national policy on blood borne viruses and healthcare workers are discussed. J. Med. Virol. 86:235–240, 2014. © 2013 Wiley Periodicals, Inc.

A case is described of a woman with acute hepatitis C infection whose partner had chronic hepatitis C infection and where heterosexual contact was the only major risk factor. Infection of both partners was confirmed serologically and by the finding of virus RNA by reverse transcription and polymerase chain reaction amplification. Nucleotide sequence analysis of the NS5 region (RNA polymerase) was used to show that both partners were infected with virus of the same genotype (1a). The nucleotide sequence of virus RNA found in the female patient is closest to variants cocirculating in the male contact, consistent with transmission having occurred between the two.

Acute viral hepatitis affects all ages worldwide. Hepatitis E virus (HEV) is increasingly recognized as a major cause of acute hepatitis in Europe. Because knowledge of its characteristics is limited, we conducted a retrospective study to outline demographic and clinical features of acute HEV in comparison to hepatitis A, B and C in Lothian over 28 months (January 2012 to April 2014). A total of 3204 blood samples from patients with suspected acute hepatitis were screened for hepatitis A, B and C virus; 913 of these samples were also screened for HEV. Demographic and clinical information on patients with positive samples was gathered from electronic patient records. Confirmed HEV samples were genotyped. Of 82 patients with confirmed viral hepatitis, 48 (59%) had acute HEV. These patients were older than those infected by hepatitis A, B or C viruses, were more often male and typically presented with jaundice, nausea, vomiting and/or malaise. Most HEV cases (70%) had eaten pork or game meat in the few months before infection, and 14 HEV patients (29%) had a recent history of foreign travel. The majority of samples were HEV genotype 3 (27/30, 90%); three were genotype 1. Acute HEV infection is currently the predominant cause of acute viral hepatitis in Lothian and presents clinically in older men. Most of these infections are autochthonous, and further studies confirming the sources of infection (i.e. food or blood transfusion) are required.

Aims Previously, a retrospective cohort study found no increased risk of acute pancreatitis with current or recent use of exenatide twice daily compared with use of other anti-diabetic drugs. This follow-up study investigated incident acute pancreatitis, with the use of a different data source and analytic method, in patients exposed to exenatide twice daily compared with patients exposed to other anti-diabetic medications. Methods A large US health insurance claims database was used. Eligible patients had ≥months continuous enrollment without a claim for pancreatitis and a claim for a new anti-diabetic medication on or after 1 June 2005 to 31 March 2009. Cases of acute pancreatitis were defined as hospitalized patients with an Internation Classification of Disease9 code of 577.0 in the primary position. A discrete time survival model was used to evaluate the relationship between exenatide twice daily and acute pancreatitis. Results Of 482034 eligible patients, 24237 initiated exenatide twice daily and 457797 initiated another anti-diabetic medication. Initiators of exenatide twice daily had more severe diabetes compared with initiators of other anti-diabetic medications. After adjustments for propensity score, insulin and use of medication potentially associated with acute pancreatitis, the odds ratio with exenatide twice daily exposure was 0.95 (95%CI 0.65–1.38). A secondary analysis that examined current, recent and past medication exposure found no increased risk of acute pancreatitis with exenatide twice daily, regardless of exposure category. Conclusion This study indicates that exposure to exenatide twice daily was not associated with an increased risk of acute pancreatitis compared with exposure to other anti-diabetic medications. These results should be interpreted in light of potential residual confounding and unknown biases.

The Canadian Century Research Infrastructure (CCRI) began with the development of designs for large representative samples of the decennial census from 1911 to 1951 and continued with the development of sophisticated SPIDER software for data entry and processing. This work builds on previous research projects in several ways, including the use of digital images within an integrated suite of Java-based software programs. By describing the theoretical and practical questions addressed in the CCRI initiative, the authors seek to contribute to international efforts to enhance construction of historical databases for systematic research on economic, social. and political change.

Infliximab plus methotrexate (MTX) is approved for the treatment of rheumatoid arthritis (RA). Based on the benefit/risk profile of this combination therapy, lower doses of MTX would be preferable when infliximab efficacy can be maintained. We evaluated the ability of patients receiving infliximab plus MTX to achieve and maintain a clinical response while the dose of MTX was tapered.Infliximab infusions were administered at a minimum dosage of 3 mg/kg at 8-week intervals (following three loading doses at weeks 0, 2, and 6) to patients who had an inadequate response to MTX. MTX tapering was initiated at week 22 or later when at least a 40% improvement in the combined tender and swollen joint count was achieved; dosages were reduced by 5 mg every 8 weeks to a protocol-specified minimum dosage of 5 mg per week. If the required dosage of MTX after a flare was greater than the baseline dosage, the patient was considered a treatment failure.Of the 210 patients enrolled, 159 (76%) achieved a 40% or better improvement in the combined tender and swollen joint count and had their MTX doses tapered. In these 159 responders, the median (mean) dose of MTX was reduced from 15 (16.5) mg per week at baseline to 5 (7.1) mg per week at week 54. From the time of initial response, 79% of these patients had a zero- or a one-vial increase in infliximab, corresponding to an approximate dose increase of 1 mg/kg, through week 54.Approximately 75% of the patients participating in this trial achieved at least a 40% reduction in the combined swollen and tender joint count (correlating with an American College of Rheumatology 20% [ACR20] response in 83% of patients) while reducing the mean MTX dose by 57%.

A sample of several different bulk granular fertilizer materials sold at six, geographically diverse Mississippi cooperatives were obtained, sieved, and chemically analyzed. Samples of ‘small,’ ‘medium,’ and ‘large’ particles for each material-cooperative combination were analyzed for nitrogen, phosphate, potash, or lime content as appropriate. The size distributions of the same type of fertilizer materials varied widely depending on the location of the cooperative where the sample was taken. However, the chemical content of various sizes of particles of a given type of fertilizer were not significantly different. In addition, the chemical content was typically very close to the nominal chemical content. The one exception was triple super phosphate where the measured content was near 44.3% while the nominal value was 46%.

Tests for the feasibility of a variable rate applicator using a buggy-type spreader were first run for potash, ammonium nitrate, and triple super phosphate. A second study compared the spread patterns for potash when using buggy and truck-type spreaders under similar wind conditions. The mass flow rate test results for potash, ammonium nitrate, and triple super phosphate showed a significant, linear relationship between gate opening and flow rates. Buggy swath deposit coefficients of variation (CVs) of . 15% were only obtained with swath widths of 2 or 3 m (6.5 or 10 ft). The average CV for potash deposits from the buggy and a truck were similar under the conditions tested. At similar application rates, the truck and buggy produced effective swath widths of 5 and 4 m (16 and 13 ft), respectively. Most across-the-swath and in-the-direction-of-travel deposit CVs exceeded 15%. For fertilizer applications with a CV of 15%, one would expect the maximum deposit within a given swath to be 80% (i.e., maximum/minimum deposit ratio = 1.8) larger than the smallest deposit. While a CV of 15% is considered to be a desirable target, the levels of variation in fertilizer deposits can still be large.

Field tests were run using sample pans to assess the effect of wind speed, wind direction, fertilizer material, and swath spacing on both the uniformity and recovery of the applications. The pan deposits were used in conjunction with a computer program to develop the overlapped swath deposits. The uniformity of the deposits were material, wind speed, wind direction, and swath width dependent. The up-and-down and racetrack application patterns are equally effective with respect to the uniformity of the applied granular materials. A coefficient of variation (CV) of 15% corresponds to a maximum deposit that is 70% larger than the minimum deposit. Ammonium nitrate CVs . 15% were obtained under low speed, cross winds when swath widths were generally

A small plot pesticide evaluation system is described that includes a computer-controlled tractor-mounted spray system, an automatic pipetter for filling bottles used on the spray tractor, and a computer program for computation of amounts of adjuvants and pesticides to be added to a pre-set volume of carrier to result in a specific mixture concentration. Benefits of the system include fast, accurate mixing of chemicals in replicate, precise spraying of pesticide, computer-controlled rinsing of the system, and reduced operator fatigue.

The variation of baseline levels of uranium in soil and stream sediments over Europe is described, based on new data prepared by the Forum of European Geological Surveys (FOREGS). The samples have been collected and analysed according to the protocols established for the International Union of Geological Sciences/International Association of Geochemistry and Cosmochemistry (IUGS/IAGC) Working Group on Global Geochemical Baselines. The baseline levels of U vary between 0·21 to 53 mg kg-1 in topsoils, 0·19 to 30 mg kg-1 in subsoils and < 1 to 59 mg kg-1 in stream sediments. There is generally good agreement between the levels of U in the three sample types, and the median concentration in all three media is approximately 2 mg kg-1. The most anomalous baseline levels occur over the Variscan orogen, especially areas into which late postorogenic radiothermal high heat production (HHP) granites were emplaced. Spiderdiagrams based on trace element levels and rare earth element (REE) plots, confirm the a...

Effects of droplet size and volumetric application rate of tractor-applied lambda cyhalothrin (Karate Z 2.08 SC) on larval tobacco budworm, Heliothis virescens (F.), mortality and insecticide deposition on and within the canopy of mature cotton were explored by use of a laboratory bioassay incorporating field-sprayed cotton and a field trial incorporating natural insect infestations. Insecticide was applied in all combinations of three distinct droplet sizes and three volumetric application rates. Mortality of third-instar tobacco budworm occurring in leaf-disk bioassays was highly correlated with insecticide deposits (microg/leaf disk) at upper- and midcanopy levels. At the upper canopy level, mortality was negatively correlated with volumetric application rate and was not significantly correlated with droplet size. Deposit was negatively correlated with volumetric application rate at the lower plant level and larval mortality decreased with increasing droplet size. Results from this study do not support the recommendations of high volumetric application rates; and although droplet size was less influential than volumetric application rate in deposit and insect mortality, the data indicate a significant trend toward increased midcanopy larval mortality with smaller droplets.

Laboratory and field tests were conducted to evaluate the magnitude and uniformity of spray deposits from several fan nozzle types. The laboratory and field average percent spray recoveries were typically in excess of 80% and often exceeded 90%. Ninety-four percent of the field deposit coefficients of variation (CV) were larger than the corresponding laboratory CVs. The down-and-back @ 45° nozzle orientation improved the uniformity of spray deposits in both laboratory and field tests. These comparative CV results confirm similar results from prior studies for other types of fan nozzles. Regression equations were developed to predict ‘percent recovery’ and ‘CV’ for both the laboratory and field data. The ratios of the maximum-to-minimum deposits from all treatments were found to be non-linearly related to the CVs of the deposits. A CV of 15% corresponded to a maximum-to-minimum deposit ratio of about 1.7 indicating that a CV of about 15% or less is a desirable goal for any liquid or granular application. Only one third of the original treatments had field CVs =15% and, thus, were considered to be treatments that would be recommended to producers and applicators.

Studies were conducted to determine the effects of droplet size, leaf morphology, and a spray thickener on pesticide spray deposition using chlorpyrifos as the indicator compound. The predicted deposition efficiencies for 140 µm droplets were 99, 77, 65, and 55%, respectively, for cocklebur, entireleaf morninglory, velvetleaf, and coffee senna leaves. Predicted deposition efficiencies decreased as droplet size increased for all four leaf types. The slopes of the linear regression equations indicated that deposition efficiency would decrease by 16, 10, 8, and 6% , respectively, with each 100 µm increase in droplet diameter. Addition of a viscosity modifying adjuvant did not improve the deposition efficiency on coffee senna leaves.

The recently discovered hepatitis G virus (HGV) or GB virus C (GBV-C) is widely distributed in human populations, and homologues such as HGV/GBV-C CPZ and GBV-A are found in a variety of different primate species. Both epidemiological and phylogenetic analyses support the hypothesis that GB viruses coevolved with their primate hosts, although their degree of sequence similarity appears incompatible with the high rate of sequence change of HGV/GBV-C over short observation periods. Comparison of complete coding sequences (8,500 bases) of different genotypes of HGV/GBV-C showed an excess of invariant synonymous sites (at 23% of all codons) compared with the frequency expected by chance (10%). To investigate the hypothesis that RNA secondary-structure formation through internal base pairing limited sequence variability at these sites, an algorithm was developed to detect covariant sites among HGV/GBV-C sequences of different genotypes. At least 35 covariant sites that were spatially associated with potential stem-loop structures were detected, whose positions correlated with positions in the genome that showed reductions in synonymous variability. Although the functional roles of the predicted secondary structures remain unclear, the restriction of sequence change imposed by secondary-structure formation provides a mechanism for differences in net rate of accumulation of nucleotide substitutions at different sites. However, the resulting disparity between short- and long-term rates of sequence change of HGV/GBV-C violates the assumptions of the “molecular clock.” This places a major restriction on the use of nucleotide or amino acid sequence comparisons to calculate times of divergence of other viruses evolving under the same structural constraints as GB viruses.

Background and Objectives: The aim of this study was to determine the hepatitis C virus (HCV) infection rate of recipients of different batches of anti–D immunoglobulin associated with an outbreak of HCV infection which occurred in 1977 and its relationship to the polymerase chain reaction (PCR) status of the implicated batches. This study was undertaken to determine the predictive value of HCV genome detection and quantification for subsequent infection in recipients of an HCV–contaminated anti–D immunoglobulin product for intravenous use. Materials and Methods: Sera from recipients of anti–D were tested by HCV enzyme immunoassay and if found positive were subsequently tested by recombinant immunoblot assay and HCV PCR in a national HCV anti–D screening programme set up in 1994. The HCV status of 1,342 known recipients of infectious or potentially infectious batches has been compared to the amount of HCV RNA in the anti–D batch they received so as to determine the value of PCR in the prediction of infectivity in immunoglobulin preparations. Results: It has been demonstrated that HCV–infected plasma derived from batches of anti–D showing levels of viral genome in excess of 104 genomes per millilitre led to infection of up to 60% of recipients. In contrast, batches with undetectable levels of HCV genome very rarely transmitted infection. Conclusions: The presence of HCV RNA in intravenous immunoglobulin preparations which have not undergone a specific viral inactivation step is a predictor of HCV infection in recipients.

As a part of it restructuring of the space mission design process, the Jet Propulsion Laboratory is investigating a model-driven concept for capturing system level requirements for space missions.

We have investigated the ability of different subgenomic fragments to reproduce the phylogenetic relationships observed between six complete genome sequences of GBV-C/hepatitis G virus (HGV). While similar relationships were observed following analysis of part of the 5' non-coding region (5'NCR), for the coding region they were not accurately reproduced for some large fragments or for the majority of fragments of 300 or 600 nucleotides. Analysis of 5'NCR sequences from a large number of isolates, including newly obtained sequences from Pakistan, Zaïre and Scotland, produced separate groupings of Asian, African and European/North American variants. These groupings are associated with specific polymorphisms in the 5'NCR, many of which were covariant and consistent with a proposed secondary structure for this region. The relatively low level of amino acid sequence variation observed between these geographically and phylogenetically defined groups of variants suggests that they are unlikely to display significant biological differences.

From August 1993 to May 1994 there were 1505 inpatient and 2590 outpatient chemotherapy treatment episodes at the Clatterbridge Centre for Oncol- ogy. A total of 21 thromboembolic events, including two arterial events, were recorded among these patients at a median of 8 weeks from the start of treatment (range 0–14 weeks), and 2 episodes occurred at the time of first presentation. The median age of the patients developing thromboembolism was 53 (range 29–75) years, and there were 14 women and 7 men. In all, 13 of the events (62%) occurred in patients receiving inpatient treatment and 8 (38%), in outpatients. The incidence of thrombosis per treatment episode in inpatients was therefore 0.008 as compared with 0.003 in outpatients. The associated malignancies were breast cancer (5), testicular cancer (4), lung cancer (3), ovarian cancer (3) and non-Hodgkin’s lymphoma (2), with bladder, colon, anal and brain cancer providing 1 case each. The following bulky pelvic or para-aortic disease was present in 9 patients: testicular cancer (3), ovarian cancer (3), lymphoma (2) and bladder cancer (1). In all, 20 of the 21 thrombotic episodes were successfully treated, with 1 patient dying from the complications of venous gangrene. Thromboembolic disease is a relatively common and important cause of morbidity and mortality in cancer patients that requires early recognition and treatment.

Variants of hepatitis C virus (HCV) have been classified by nucleotide sequence comparisons in different regions of the genome. Many investigators have defined the ranges of sequence similarity values or evolutionary distances corresponding to divisions of HCV into types, subtypes and isolates. Using these criteria, novel variants of HCV from Vietnam, Thailand and Indonesia have been classified as types 7, 8, 9, 10 and 11, many of which can be further subdivided into between two to four subtypes. In this study, this distance-based method of virus classification was compared with phylogenetic analysis and statistical measures to establish the confidence of the groupings. Using bootstrap resampling of phylogenetic trees in several subgenomic regions (core, E1, NS5) and with complete genomic sequences, we found that one set of novel HCV variants ('types 7, 8, 9 and 11') consistently grouped together into a single clade that also contained type 6a, while 'type 10a' grouped with type 3. In contrast, no robust higher-order groupings were observed between any of the other five previously described HCV genotypes (types 1-5). In each subgenomic region, the distribution of pairwise distances between members of the type 6 clade were consistently bi-modal and therefore provided no justification for classification of these variants into the three proposed categories (type, subtype, isolate). Based on these results, we propose that a more useful classification would regard all these variants as subtypes of type 6 or type 3, even though the level of sequence diversity within the clade was greater than observed for other genotypes. Classification by phylogenetic relatedness rules out simple sequence similarity measurements as a method for assigning HCV genotypes, but provides a more appropriate description of the evolutionary and epidemiological history of a virus.

Optical fibres are being used to replace electrical cables for monitoring the immediate environment and controlling equipment, wherever there is a flammable atmosphere in the mining and chemical industries. The optical fibre based equipment was believed to be intrinsically safe, therefore suitable for use in such environments, but recent work has shown this to be untrue. A model is presented, simulating a fibrous agglomerate, in a flammable atmosphere, exposed to laser radiation and re-emitting the energy in the form of heat. Uniform temperature and concentrations are assumed throughout the reaction zone for simplicity, facilitating the inclusion of detailed chemical reaction schemes. Heat transfer is modelled by radiation and Newtonian cooling. Various parameters of the system are altered in an attempt to ascertain the most hazardous situation for a given geometry and gas concentration. The relationships between the various parameters and criticality are then shown, which leads to a tentative prediction of a minimum safe power level at which laser-based control and sensing systems can be operated in a flammable atmosphere of H"2 in air.

An 18-month survey of 31 water systems in North America was conducted to determine the factors that contribute to the occurrence of coliform bacteria in drinking water. The survey included analysis of assimilable organic carbon (AOC), coliforms, disinfectant residuals, and operational parameters. Coliform bacteria were detected in 27.8% of the 2-week sampling periods and were associated with the following factors: filtration, temperature, disinfectant type and disinfectant level, AOC level, corrosion control, and operational characteristics. Four systems in the study that used unfiltered surface water accounted for 26.6% of the total number of bacterial samples collected but 64.3% (1,013 of 1,576) of the positive coliform samples. The occurrence of coliform bacteria was significantly higher when water temperatures were > 15 degrees C. For filtered systems that used free chlorine, 0.97% of 33,196 samples contained coliform bacteria, while 0.51% of 35,159 samples from chloraminated systems contained coliform bacteria. The average density of coliform bacteria was 35 times higher in free-chlorinated systems than in chloraminated water (0.60 CFU/100 ml for free-chlorinated water compared with 0.017 CFU/100 ml for chloraminated water). Systems that maintained dead-end free chlorine levels of < 0.2 mg/liter or monochloramine levels of < 0.5 mg/liter had substantially more coliform occurrences than systems that maintained higher disinfectant residuals. Free-chlorinated systems with AOC levels greater than 100 micrograms/liter had 82% more coliform-positive samples and 19 times higher coliform levels than free-chlorinated systems with average AOC levels less than 99 micrograms/liter. Systems that maintained a phosphate-based corrosion inhibitor and limited the amount of unlined cast iron pipe had fewer coliform bacteria. Several operational characteristics of the treatment process or the distribution system were also associated with increased rates of coliform occurrence. The study concludes that the occurrence of coliform bacteria within a distribution system is dependent upon a complex interaction of chemical, physical, operational, and engineering parameters. No one factor could account for all of the coliform occurrences, and one must consider all of the parameters described above in devising a solution to the regrowth problem.

Absence of dormancy and good malting quality are significant targets of many barley (Hordeum vulgare L.) breeding programs. Expression of dormancy is strongly affected by the environment, and malting quality assays are expensive. Both groups of characters would therefore be suitable for marker-assisted selection. The objective of this study was to identify quantitative trait loci (QTL) controlling germination and malting quality characters in a cross between the spring barley genotypes 'Blenheim' and E224/3 as an initial step in the development of a marker-assisted selection scheme. The characters were measured on a random sample of doubled haploid lines from the cross grown in replicated trials each year from 1989 to 1992. The QTL were revealed by regression analysis of the data with marker scores from 120 mapped polymorphic loci. The QTL controlling hot water extract were located on barley Chromosomes 2, 3, and 7. Milling energy was largely controlled by a factor on Chromosome 7, a region also associated with extract viscosity. The denso dwarfing gene on Chromosome 3 was associated with a reduction in grain N but this was found to be a dilution effect as the locus had previously been found to be associated with an increase in grain yield. The germination characters showed little relationship with each other, possibly reflecting different mechanisms of control.

The bromate-ferroin clock reaction is studied experimentally and the dependence of the clock or induction timetcl on the initial concentration of various reactants determined. Particular attention is paid to the dependence oftclcl on the initial bromide ion concentration [Br−]0. An analytical theory is also derived based on a subset of the Field-Koros-Noyes mechanism. This analysis reveals several features, including exponential decay of [Br−] during the induction period followed by a super-exponential decay in the actual clock event, a linear relationship betweentcl, and ln[Br−] over a wide range of [Br−]0, but departures from this at higher (and lower) concentrations. These features are all confirmed essentially quantitatively by the experimental results. The theory also predicts, and the experiments confirm, that there is a critical bromide ion concentration marking the end of the induction period. This study then provides a firm basis from which to interpret and predict the behaviour of this system in a wider range of experimental situations (such as the reaction-diffusion waves in unstirred media).

A model is presented to assist in the quantification of the ignition hazard associated with the application of optical fibre technology for sensing and control in potentially flammable atmospheres. Ignition arises if radiation from a fractured fibre impinges on a solid particle or surface causing local heating. Uniform temperature and concentrations are assumed throughout the reaction zone for simplicity, allowing realistic and detailed kinetic schemes. Heat transfer is modelled by Newtonian cooling and radiation, with convective effects assumed to be suppressed by the fibrous nature of the most hazardous target materials. Results are presented, initially for H 2 /air mixtures, in terms of a critical hot surface temperature. The variation of T h , cr with mixture composition and the diameter of the optical beam are determined, along with the influence of various physical parameters characterising the absorption and heat transfer processes. Results are also presented for ‘wet’ CO and di-ethyl ether oxidation. The critical temperatures are converted to critical optical powers using a semi-empirical fit to experimental data. Despite the approximations invoked, the predicted critical data reproduce the main observed trends, show semi-quantitative agreement with experimental results and correlate with known combustion parameters, such as the appropriate auto-ignition temperatures.

SUMMARY We present profiles of the vertical distribution of bromine in cores of the late Permian (Zechstein) Boulby Halite Formation (EZ3 Na) from lower Teesside and from the potash field around Boulby Mine, Staithes, North Yorkshire. The profile for the Teesside core shows that the bromine content of the halite there (and therefore the salinity of the originating brine) lies in the lower part of the range regarded as normal for marine-derived brines throughout deposition of the formation and increases only slightly near the top. The bromine content of the Boulby Halite in the potash field core is generally slightly greater than that in the Teesside core, but, as predicted by conventional theory, increases sharply in the Boulby Potash Member near the top of the formation. Comparison of the two bromine concentration profiles suggests a close correlation. This suggested correlation needs to be tested against other bromine profiles but, if correct, implies (a) that closely sampled bromine profiles are a useful tool in the correlation of salt deposits, and (b) the Boulby Potash is entirely, or almost entirely, younger than the Boulby Halite of Teesside, possibly indicating basin-shrinkage.

Spray deposits associated with an automated spray chamber developed at Mississippi State University were evaluated. The data reported herein indicate that: (1) the deposits correspond to the calibrated volumes applied per area, (2) the variation among replications within sampling locations (CV = 12.8%) was substantially less than the variation among replication/sampling location combinations (CV = 37.2%), (3) the deposits were most uniformly deposited in the center 16 cm of the spray deposit patterns for a given nozzle-pesticide combination, and (4) both the % recovery and the shape of some spray deposit patterns varied among the four insecticides tested. These results suggest that researchers could easily be testing insecticide-nozzle combination effects rather than testing for nozzle- or insecticide-effects per se. There remains a need for a quick, accurate method for quantifying pesticide (insecticide, herbicide or fungicide) deposits.

A computerized spray chamber for rapid implementation of spray deposit experiments was developed and evaluated. The system has been in use for a number of months and has significantly improved the efficiency of running spray-related laboratory experiments. The main features of the system include time-delay system to clear spray out of the chamber before the operator opens the door, charcoal filter to filter the air before exiting the building, a spray table with adjustable height, variable nozzle speed from 0.8 to 9.33 km/h (0.5 to 5.8 mph), nozzle mounting bracket that is supplied with air pressure of 0 to 412 kPa (0 to 60 PSI), liquid pressure of 0 to 412 kPa (0 to 60 psi), and 12 Volt DC power source to accommodate hydraulic, pneumatic, or rotary (electrical) atomizers. The pressures and travel speed are displayed during an entire spray run. Electronic measurements indicated that the system was able to maintain repeatability of speed of greater than 98%. This paper describes the mechanical and electrical design and the operation of the system.

A model is presented regarding the mechanistic properties associated with the interaction of hydrogen with nanoporous palladium (np-Pd) films prepared using a spontaneous galvanic displacement reaction (SGDR), which involves PdCl(2) reduction by atomic Ag. Characterization of these films shows both chemical and morphological factors, which influence the performance characteristics of np-Pd microcantilever (MC) nanomechanical sensing devices. Raman spectroscopy, uniquely complemented with MC response profiles, is used to explore the chemical influence of palladium oxide (PdO). These combined techniques support a reaction mechanism that provides for rapid response to H(2) and recovery in the presence of O(2). Post-SGDR processing via reduction of PdCl(2)(s) in a H(2) environment results in a segregated nanoparticle three-dimensional matrix dispersed in a silver layer. The porous nature of the reduced material is shown by high resolution scanning electron microscopy. Extended grain boundaries, typical of these materials, result in a greater surface area conducive to fast sorption/desorption of hydrogen, encouraged by the presence of PdO. X-ray diffraction and inductively coupled plasma-optical emission spectroscopy are employed to study changes in morphology and chemistry occurring in these nanoporous films under different processing conditions. The unique nature of chemical/morphological effects, as demonstrated by the above characterization methods, provides evidence in support of observed nanomechanical response/recovery profiles offering insight for catalysis, H(2) storage and improved sensing applications.

D. B. Smith writes: By combining an analysis of wireline log profiles with direct observation of borehole cores, Dr D. W. Holliday presented welcome new evidence supporting the view of earlier workers that late Permian sedimentation patterns became increasingly uniform with time as relief diminished and depositional basins gradually merged. There is reasonable agreement, strengthened by the new evidence, that this increasing uniformity became a major sedimentary influence after the deposition of basin-filling halite at the end of Cycle EZ2 (and its supposed equivalent in the East Irish Sea Basin), and increasingly uniform log responses over ever-widening areas are an accepted corollary in strata from the base of Cycle EZ3 onwards. However, in claiming (p. 353) that a close correspondence in geophysical log patterns of the late Permian rocks of the Vale of Eden and on the margins of the Southern North Sea Basin suggests that there was a persistent cross-Pennine connection from EZ1 time onwards, Dr Holliday implies a firmer correlation between pre-EZ3 strata across the Pennines than the facts as presented appear to warrant. His conclusions may be correct, but much stronger and less equivocal evidence is surely required to justify them. The postulation of a pre-EZ3 cross-Pennine connection between the Vale of Eden Basin and the Southern North Sea Basin rests partly on slight similarities of the two rock sequences, but mainly on the persuasive similarity of some wireline log responses to strata penetrated in the Hilton Borehole in the west and the Harlsey (or East Harlsey) ...

Isolates of hepatitis C virus (HCV) show considerable nucleotide sequence variability throughout the genome. Comparisons of complete genome sequences have been used as the basis of classification of HCV into a number of genotypes that show 67 to 77% sequence similarity. In order to investigate whether sequence relationships between genotypes are equivalent in different regions of the genome, we have carried out formal sequence analysis of variants in the 5' non-coding region (5'NCR) and in the genes encoding the core protein, an envelope protein (E1) and a non-structural protein (NS-5). In the E1 region, variants grouped into a series of six major genotypes and a series of subtypes that could be matched to the phylogenetic groupings previously observed for the NS-5 region. Furthermore, core and E1 sequences showed three non-overlapping ranges of sequence similarity corresponding to those between different genotypes, subtypes and isolates previously described in NS-5. Each major genotype could also be reliably identified by sequence comparisons in the well conserved 5'NCR, although many subtypes, such as 1a/1b, 2a/2c and some of those of type 4, could not be reliably distinguished from each other in this region. These data indicate that subgenomic regions such as E1 and NS-5 contain sufficient phylogenetic information for the identification of each of the 11 or 12 known types and subtypes of HCV. No evidence was found for variants of HCV that had sequences of one genotype in the 5'NCR but of a different one in the E1 or NS-5 region. This suggests that recombination between different HCV types is rare or non-existent and does not currently pose a problem in the use of subgenomic regions in classification.

Total β-glucanase activity was measured in extracts of malts prepared from three winter and three spring cultivars of barley. Samples were taken at intervals during modification and, after 116 hr, from malt kilned to 65°C. Good malting varieties showed highest levels of total β-glucanase activity, with a high correlation (r = 0.926) with HWE. Angora had the highest activity in the intermediate stages of malting, least loss of activity after heating extracts to 48°C for 10 mins and least loss of activity on kilning. Separation of isozymes by HPLC9 confirmed the greater heat stability of isozyme II, but, unlike previous studies on Australian cultivars, we found considerable activity of isozyme I after kilning, even up to 85°C. However, total β-glucanase activity was destroyed by heating extracts of all varieties to 60°C. Angora showed the highest proportion of total activity as isozyme II after kilining. Cultivar differences suggested some scope for breeding varieties with increased total activity by combining high activities of each isozyme. The high correlation of total activity with HWE suggests β-glucanase activity as a rapid test of malting quality.

A spreadsheet for IBM compatible computers was written to assist with atomization decisions associated with high speed air streams and the calibration of agricultural aircraft. The “AER-ATOM” program requires up to 13 input variables. The user-supplied data are used to calculate the Volume Median Diameter (Dv0.5), the accuracy of the Dv0.5, percent of the spray volume which was initially = 154 mm in diameter, and the number of nozzles which will be needed to deliver a desired volumetric application rate (gpa of total spray). The abundant presence of significant operating or equipment variables in the Dv0.5 equations indicates that the aerial applicator has wide latitude in controlling the atomization/calibration results. Successive simulations can be made by changing the data for one or more variables. These results can be saved either in a computer file or as a printed copy for future reference. The magnitude of the calibration errors resulting from fly-ins in Mississippi indicate that the ‘AER-ATOM’ can help improve application accuracy.

A comparative study of the reproductive ecology of the zooxanthellate, scleractinian corals Porites lobata Dana and P. panamensis Verrill was conducted from 1985 to 1991 in eastern Pacific reef environments that were severly impacted by the 1982–1983 El Nino warming events. P. lobata, a presumed broadcast spawner of large colony size, is widely distributed in the equatorial eastern Pacific, whereas P. panamensis, a brooder of small colony size, is abundant only on some reefs in Panama. Both species were gonochoric with nearly 1:1 sex ratios in large study populations except for P. lobata at Cano Island that had 14% hermaphroditic colonies. Mature, unfertilized oocytes contained numerous zooxanthellae in both Porites species, and all planula developmental stages contained zooxanthellae in P. panamensis. Year-round sampling revealed high proportions of colonies with gonads, ranging from 30 to 68% in P. lobata and from 60 to 68% in P. panamensis. No clear relationship between numbers of reproductive colonies and the thermal stability of the habitat was evident in P. lobata: percent colonies with gonads at non-upwelling sites was 48 to 68% at Cano Island (Costa Rica) and Uva Island (Panama), and at upwelling sites 30 to 50% at Saboga Island and Taboga Island (Panama), and the Galapagos Islands (Ecuador). Similarly, 90% of all P. panamensis colonies were reproductive at Uva Island (a non-upwelling site), and 86% were reproductive at Taboga Island (an upwelling site). Upwelling at Taboga Island is seasonal, nevertheless P. panamensis produced mature gonads or planulae over most of the year (11 mo), whereas P. lobata exhibited reproductive activity during only 2 mo (May and June). No clear lunar periodicity was observed in P. panamensis (Taboga Island), but a high proportion of P. lobata showed increased gonadal development around full and new moon, especially at Cano and Uva Islands. Estimated fecundities were relatively high for P. lobata at Cano (4000 eggs cm-2 yr-1) and Uva (5200 eggs cm-2 yr-1) Islands, and notably low (70 to 110 eggs cm-2 yr-1) in the Galapagos Islands. P. panamensis mean fecundity at Taboga Island was 720 planulae cm-2 yr-1 or 4.0 mm3 cm-2 yr-1, which was lower than the egg volume production of P. lobata at Cano and Uva Islands (7.0 to 10.0 mm3 cm-2 yr-1). The capacity of P. lobata and P. panamensis to reproduce sexually supports the notion that eastern Pacific coral reef recovery may not be dependent on long-distance dispersal from central Pacific areas. However, sexual recruits of P. lobata are absent or uncommon at all eastern Pacific study sites while recruits of P. panamensis were common to abundant only at the Uva Island study site. Asexual fragmentation in P. lobata augments recruitment locally, but plays no role in P. panamensis recruitment.

Non-A, non-B hepatitis was recognized as a frequent consequence of blood transfusion for many years before the agent responsible, hepatitis C virus (HCV), was first cloned and sequenced in 1989 Very quickly it became apparent that viruses from different parts of the world were distinct, and after a frenzy of sequence analysis, a general picture has now emerged (1). Virus sequences can be divided into major types (identified by numbers) with nucleotide identities of70% over complete genome sequences. Each type can be subdivided into subtypes (identified by letters) with identities of between 70 and 80%. Complete genome sequences are now available for all six HCV types and for several different subtypes of type 1 (a, b, and c), 2 (a, b, and c) and 3 (a, b, and "10a"). Very similar sequence relationships are obtained by analysis of subgenomic fragments, such as individual genes encoding structural or nonstructural proteins or a region as short as 222 nt of NS5B. On the basis of such comparisons, it is possible to differentiate consistently among six major genotypes (Fig. 1), and to an increasing number of subtypes (Fig. 2), now exceeding 10 for types 1, 2, 3, 4, and 6, but with only two known for type 5. Some isolates from southeast Asia have a controversial placement in this system, since they are less divergent from each other than virus types, but more divergent than subtypes However, phylogenetic and serological evidence suggests that they represent divergent subtypes of types 3 and 6 (2,3). Fig. 1. Phylogenetic tree of HCV NS5B sequences. Nucleotide sequences for positions 7975-8196 (numbered from the polyprotein AUG initiation codon) of NS5B were analyzed using the program Phylip as described previously (76). Major branches are labeled with the type number, and minor branches with letters indicating the subtype The variant "10a" can be considered as a subtype of type 3, and the variants "7a", "7b", "8a," and so forth, as subtypes of type 6 (2,3). Fig. 2. The discovery of HCV types and subtypes. The total number of HCV types (solid line) and subtypes (broken line) is indicated by year.