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To explore the relationship of embolic particle size used in prostate artery embolisation (PAE) to patient outcomes.A systematic review of PubMed, EMBASE, and the Cochrane database was undertaken to identify all existing studies using PAE for benign prostatic hyperplasia (BPH). Inclusion criteria included prospective studies reporting baseline and 12-month International Prostate Symptom Score (IPSS) and particle size. Exclusion criteria were overlapping studies, commentaries, abstracts, and letters. Data extraction from eligible studies included the size of embolic particle, particle material, and baseline and 12-month values for the following patient outcomes: IPSS, IPSS quality of life, urinary flow rate (Q-max), prostate volume, prostate specific antigen, and post-void residual volume. A meta-regression analysis was then undertaken to examine the relationship of particle size to patient outcome measures.Six studies with a total of 687 patients were identified. Meta-regression analysis demonstrated particle size as a statistically significant (p0.001) moderator of 12-month IPSS change following PAE. No statistically significant relationships were identified with other patient outcome measures.Smaller embolic particle size is associated with a greater reduction in IPSS following PAE.

A theoretical study of classical spin waves propagating in axially magnetized, lossy ferromagnetic nanowires is considered, resulting in a model for a magnonic Bragg mirror based on an axially periodic arrangement of identical nanowire segments. While the system shows evidence of one-dimensional magnonic band gaps, with widths increasing as the inter-nanowire exchange coupling strength decreases, spin wave attenuation effects can be quite dramatic for magnetic damping constants within the range 0.001–0.1. In fact, calculated reflectance spectra for nanowire structures with a damping constant on the order of 0.01 exhibit relatively intense Bragg peaks only when the nanowire segment length is no more than an order of magnitude larger than the exchange length.

Health care organizations must adopt a culture of safety and implement effective fall prevention protocols. The teach-back method is a useful strategy for health providers to determine patient understanding of information taught to maintain a safe environment and prevent falls. PURPOSEful rounding is a proactive approach to ensure that patient assessments are accurate and research supports that patients use the call light less when nurses participate in hourly rounding. This article provides the reader with evidence-based fall prevention interventions, tips for using the teach-back method, and fall prevention tools to safely care for patients of all ages. Language: en

Background DNA sequencing to identify variants is becoming increasingly valuable in clinical settings; including matching patients to approved targeted therapies, immunotherapies, and/or clinical trials. However, accurate calling of genetic variants from sequencing still remains challenging. With little corroboration between the different tools available, patients are at risk of being treated with therapies that are unsuitable for their cancer. Methods Here we present a novel machine learning based method for the accurate identification of somatic variants in cancer patient tumour samples, with a neural network architecture from encoded raw sequencing read information of tumour/normal sample pairings into an image, enabling it to classify whether a variant is germline, somatic, or sequencing error. The model was trained and tested on in-silico spike-in data using bam-surgeon, and then validated on a multi-cancer and multi-center dataset and benchmarked against industry standard variant callers. Results The approach, called somaticNET, outperforms existing industry standard tools in sensitivity and specificity, achieving an AUROC of ∼1.00 on the bam-surgeon dataset and an AUROC of ∼0.99 on the multi-cancer multicenter dataset. The model also works faster than other variant callers, in minutes compared to hours. Conclusions Using the power of machine learning for accurate somatic variant calling can improve patient matching to approved therapies and clinical trials, thus ensuring patients are given the right therapy at the right time to treat their cancer. Legal entity responsible for the study The authors. Funding Cambridge Cancer Genomics. Disclosure G. Dubourg-Felonneau: Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. D. Rebergen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. C. Parsons: Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. H. Thompson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. J.W. Cassidy: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Cambridge Cancer Genomics. N. Patel: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics. H.W. Clifford: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Cambridge Cancer Genomics.

Highlights • A mediastinal thyroid mass discovered years after total thyroidectomy is presented. • The history, etiology, and optimal surgical approach are discussed. • The “forgotten goiter” can be safely approached through a cervical incision., Introduction A mediastinal thyroid mass discovered years after a total thyroidectomy represents an unusual and uncommon clinical situation. Few cases have been reported and controversy exists regarding the etiology of this ectopic thyroid tissue as well as the optimal surgical approach for resection. We herein describe a case of a mediastinal thyroid goiter discovered five years after a total thyroidectomy. Presentation of case A 54-year-old Hispanic female was diagnosed with a diffuse cervical goiter secondary to Hashimoto’s Thyroiditis and subsequently underwent a total thyroidectomy. Five years later the patient had a chest X-ray as part of a preoperative evaluation for an unrelated and elective surgical procedure. Significant tracheal deviation was identified. A computed tomography scan was obtained and demonstrated a well encapsulated mass in the superior mediastinum resulting in tracheal deviation and compression. This “forgotten” goiter was successfully resected utilizing a standard cervical approach and the patient recovered uneventfully. Discussion A thyroid mass within the mediastinum following a total thyroidectomy is a condition often referred to as “forgotten goiter”. Prior reported cases are few, and data is limited, with some uncertainty remaining as to the exact origin of this ectopic thyroid tissue. Possible etiologies include an incomplete removal of the thyroid gland during initial cervical thyroidectomy, or perhaps an autonomous intrathoracic goiter (AIG) – a thyroid gland located in the mediastinum, independent and with no parenchymatous or vascular connection with the cervical thyroid gland. Conclusion A trans-thoracic or sternal splitting approach is generally not required for resection of a mediastinal goiter and our experience confirms that the case of the “forgotten goiter” can be safely approached through a cervical incision as well.

A flexible route which enables access to derivatives of 4-amino-1,3-dihydroimidazo[4,5-c]pyridin-2-ones is described. Issues of selectivity, reaction safety, and low yields in original routes are overcome with the key improvements to the route, including a Negishi cross-coupling and use of a carbamate as a protecting group and intrinsic carbonyl source. The new route enables variation of C-6 and N-1 substituents.

Bottlebrush squirreltail (Elymus elymoides [Raf.] Swezey) is an important native bunchgrass for rangeland restoration in western North America. This species is taxonomically complex and has diverged into as many as four subspecies, including subsp. brevifolius, for which four geographically distinct races have been described (A, B, C, and D). Of these four races, only C occurs in the northern Intermountain West. Our objectives were to describe phenotypic and genetic variation within C and to ascertain its taxonomic status. We evaluated 32 populations of C collected across the northern Intermountain West for a battery of biomass, phenological, and functional traits in common-garden settings in the field and greenhouse. Genetic variation was assessed with the use of amplified fragment length polymorphism (AFLP) markers, and correlations were calculated among phenotypic, genetic, environmental, and geographic distance matrices with the use of Mantel tests. Values for these four distance measures were positively correlated, suggesting that environmental heterogeneity and isolation by distance are shaping ecotypic divergence driven by natural selection. We describe three phenotypic zones for C that correspond to previously established ecoregion boundaries. Because genetic data group C apart from subsp. brevifolius races A, B, and D, which originate in the Rocky Mountains and western Great Plains, the so-called race C merits description as a new subspecies apart from subsp. brevifolius.

The plethora of digital communication technologies, and their mass take up, has resulted in a wealth of interest in social network data collection and analysis in recent years. Within many such networks the interactions are transient: thus those networks evolve over time. In this paper we introduce a class of models for such networks using evolving graphs with memory dependent edges, which may appear and disappear according to their recent history. We consider time discrete and time continuous variants of the model. We consider the long term asymptotic behaviour as a function of parameters controlling the memory dependence. In particular we show that such networks may continue evolving forever, or else may quench and become static (containing immortal and/or extinct edges). This depends on the existence or otherwise of certain infinite products and series involving age dependent model parameters. We show how to differentiate between the alternatives based on a finite set of observations. To test these ideas we show how model parameters may be calibrated based on limited samples of time dependent data, and we apply these concepts to three real networks: summary data on mobile phone use from a developing region; online social-business network data from China; and disaggregated mobile phone communications data from a reality mining experiment in the US. In each case we show that there is evidence for memory dependent dynamics, such as that embodied within the class of models proposed here. © 2011 Elsevier B.V. All rights reserved.

The synthesis and structure-activity relationships of a series of novel interferon inducers are described. Pharmacokinetic studies and efficacy assessment of a series of 8-oxo-3-deazapurine analogues led to the identification of compound 33, a potent and selective agonist of the TLR7 receptor with an excellent in vivo efficacy profile in a mouse model.

Anticonvulsant hypersensitivity syndrome is a severe, potentially life-threatening, reaction to the aromatic anticonvulsant medications. Reported here is a case of anticonvulsant hypersensitivity syndrome secondary to phenobarbital in a 2-year-old boy; he responded to drug withdrawal, corticosteroids, and intravenous immunoglobulin. The literature regarding treatment of this syndrome is reviewed.

Purpose The purpose of this study was to investigate the feasibility of clot visualization in small sinus and cortical veins with contrast enhanced MRA in a cerebral venous thrombosis animal model using a blood pool contrast agent, Gadofosveset, and high spatial resolution imaging. Material and methods For induction of cerebral venous thrombosis a recently developed combined interventional and microsurgical model was used. Cerebral sinus and cortical vein thrombosis was induced in six pigs. Two further pigs died during the procedure. Standard structural, time-of-flight- and phase contrast-angiograms were followed by fast time resolved high resolution 3D MRA (4D MRA) and subsequent high spatial resolution 3D MRA in the equilibrium phase with and without addition of parallel imaging. Visualization of the clots using the different sequences was subjectively compared and contrast-to-noise ratio (CNR) was assessed. Results In the remaining six animals the procedure and MR-imaging protocol including administration of Gadofosveset was successfully completed. The 3D high resolution MRA in the equilibrium phase without the addition of parallel imaging was superior to all the other applied MR measurement techniques in terms of visualization of the clots. Only applying this sequence bridging vein thromboses were also seen as a small filling defect with a high CNR of >18. Conclusion Only the non-accelerated high spatial resolution 3D MRA in the equilibrium in conjunction with the blood pool agent Gadofosveset allows for high-contrast visualization of very small clots in the cerebral sinus and cortical veins. Statement clinical impact Detection of cortical vein thrombosis is of high clinical impact. Conventional MRI sequences often fail to visualize the clot. We could demonstrate that, in contrast to conventional sequences, with high spatial resolution 3D MRA in the equilibrium in conjunction with the blood pool agent Gadofosveset very small clots in the cerebral sinus and cortical veins could be successfully visualized. We think that with the presented approach cortical vein thrombosis might also be sufficiently visualized in patients.

The Malleefowl is a ground-dwelling bird species that has declined in distribution and abundance in Australia since European settlement. These declines have been exacerbated in the Western Australian wheatbelt by the extensive clearing of native vegetation for agricultural development. A wealth of opportunistic, presence-only data exists for this species but absence data required for distribution modelling is lacking. This situation is typical of many species distribution datasets. We sought to establish the distribution of malleefowl within the Western Australian wheatbelt (210 000 km2) and their choice of habitat within this broad region. We supplemented a large presence-only dataset of malleefowl sightings with absence data derived from a bird atlas scheme and used these data to effectively predict the distribution of the species for the wheatbelt using a combined GAM/GLM approach. Both datasets were derived largely from community sightings. The distribution of malleefowl within the Western Australian wheatbelt was associated with landscapes that had lower rainfall, greater amounts of mallee and shrubland that occur as large remnants, and, lighter soil surface textures. This study illustrates how community knowledge, coupled with solid ecological understanding, can play a key role in developing the knowledge base to inform conservation and management of species in agricultural landscapes.

The synthesis of a range of novel amine-containing structures and their primary potency as inhibitors of HIV-1 fusion via blocking of the CCR5 receptor is described. The development of the medicinal chemistry strategy and SAR's which led to the identification of the piperidine amide compounds 33 and 36 as excellent leads for further evaluation is described, along with key physicochemical data which highlighted their lead potential.

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is the most common mitochondrial disease due to mitochondrial DNA (mtDNA) mutations. At least 15 distinct mtDNA mutations have been associated with MELAS, and about 80% of the cases are caused by the A3243G tRNA(Leu(UUR)) gene mutation. We report here a novel tRNA(Val) mutation in a 37-year-old woman with manifestations of MELAS, and compare her clinicopathological phenotype with other rare cases associated tRNA(Val) mutations.

We cannot be certain when the next influenza pandemic will emerge, or even whether it will be caused by avian influenza (H5N1) or some unrelated virus. However, we can be certain that an influenza pandemic will occur. The United States is leading the scientific effort to contain the pandemic through vaccine studies and antiviral studies. The need for pandemic influenza preparedness is extensive and expensive. Planning entails increased development of antivirals and vaccines, effective surveillance systems not only for people, but in agriculture, effective communication systems, plans to continue essential services, identification of health care priorities, and thorough guidelines for care. Critical care nurses, as well as all health care professionals, need to consider where their personal and professional obligations meet and end. There should already be discussions of contingency plan of the institution in which they are employed and the community in which they live. Additionally, a personal plan for their families with regard to economics, safety, and optimizing personal health outcomes during such a crisis should be considered. As many have said, "It is not a matter of if, but rather of when." Although the pandemic might not be the avian flu, history has taught us that pandemics surface with little warning and can have devastating effects on human lives, and can over tax the already fragile health care system.

Acute and critical care nurses must maintain a current knowledge base for advancing science and providing direct care for patients. When an infectious process is involved, it is the practicing nurse who must be knowledgeable in treatment and prevention modalities. The integument is the body's first line of defense for invading bacteria. This barrier to bacteria is followed by inflammation and adaptive immunity, the second and third lines of defense against infectious bacteria. It is acute and critical care nurses, however, who should be the first line of defense in preventing the spread of infectious disease. Modern medicine and common sense interventions reviewed in this article are the patient's best defense to good health and wellness when used by nurses.

Patients in the critical care setting are at high risk for infection because their normal host defenses are compromised. Critical care patients frequently have complicated, multisystem, mixed infections that can be life threatening. Optimal patient outcomes are the result of (1) early identification of signs and symptoms of infection; (2) nursing knowledge about common antimicrobials and their side effects and adverse reactions; (3) obtaining cultures before starting empiric therapy with antimicrobials; (4) consulting as needed with the infection control team; (5) practicing basic measures of infection control, such as hand washing; and (6) using special isolation precautions when the patient's condition warrants special care. The nurse also needs to be vigilant to the signs of toxicity from antimicrobial therapy. These interventions can save the critical care patient's life, prevent others from becoming infected, and save the hospital precious fiscal resources.

A sewer main serving a large municipal wastewater system ruptured, discharging approximately 3,000,000 gallons (11,355,000 L) of raw human sewage into a multi-branched tidal creek estuary along the US East Coast. The biochemical oxygen demand caused severe hypoxia in the system, causing a large fish kill. The sewage load led to high fecal coliform bacteria concentrations in the creek (maximum of 270,000 CFU 100ml(-1)), which declined in an approximate logarithmic manner over the first few days. The spill caused elevated sediment fecal coliform bacteria and enterococcus counts that declined much more gradually than water column counts. Persistence of relatively high concentrations of fecal indicator bacteria in sediments for several weeks after the spill suggests that sediment sampling should be included in response to major sewage spills. The high concentration of nutrients in the spilled sewage led to several algal blooms. However, nutrient concentrations in the water column declined rapidly, demonstrating the value of conserving marshes because of their pollutant filtration function.

Osteoporosis is a nationwide health care concern affecting millions of Americans. Health care dollars to prevent and treat osteoporosis are needed. Osteoporosis-related injuries and resulting disabilities, and consequent admissions to hospitals, nursing homes, and long-term care facilities is costing billions of dollars for care and treatment. Healthy lifestyle choices including vitamin and mineral therapy; safe home environments; a diet replete with calcium, vitamin D, and protein; weight-bearing and resistance exercises; and fall prevention programs for home-bound and hospitalized elders are needed to prevent osteoporosis-related fractures and injuries. Nurses must educate the public on osteoporosis and osteoporosis-prevention activities. Research in nursing, pharmacy, and allied health fields such as physical therapy and nutrition must expand to improve understanding of the risks associated with osteoporosis and to evaluate health-promotion and disease- prevention activities. Interdisciplinary partnerships should be established to study the issues, prevention, and treatment modalities of this "silent killer."

Tidal creeks are commonly found in low energy systems on the East and Gulf Coasts of the United States, and are often subject to intense watershed human development. Many of these creeks are receiving urban and suburban runoff containing nutrients, among other pollutants. During the period 1993–2001, we studied three tidal creeks located in southeastern North Carolina, a rapidly urbanizing area. All three creeks received anthropogenic nutrient loading. Oligohaline to mesohaline stations in upper tidal creek regions had much higher nutrient (especially nitrate–N) concentrations than lower creek areas, and hosted spring and summer phytoplankton blooms that at times exceeded 200 μg chlorophyll a l −1 . Phytoplankton biomass during winter was low at all stations in all three creeks. Spring and summer nutrient addition bioassay experiments were conducted to characterize the nutrients limiting phytoplankton growth. Water from high salinity stations in all three creeks always showed significant positive responses to nitrate–N inputs, even at concentrations as low as 50 μg N l −1 . Low salinity stations in upper creek areas often showed significant responses to nitrate–N inputs, but on occasion showed sensitivity to phosphorus inputs as well, indicating the influence of anthropogenic nitrate loading. During several experiments, one of the upper stations showed no positive response to nutrient inputs, indicating that these stretches were nutrient replete, and further phytoplankton growth appeared to be light-limited either by phytoplankton self-shading or turbidity. Water from upper creek areas yielded much higher chlorophyll a concentrations in bioassay experiments than did lower creek water. In general, these urbanizing tidal creeks were shown to be very sensitive to nitrogen loading, and provide a physical environment conducive to phytoplankton bloom formation in nutrient-enriched areas. Tidal creeks are important ecological resources in that they are considered to be nursery areas for many species of fish and shellfish. To protect the ecological function of these small, but very abundant estuarine systems, management efforts should recognize their susceptibility to algal blooms and focus on control of nonpoint source nutrient inputs, especially nitrogen.

A variation of the oscillating gradient spin echo method had been developed, which isolates temporal frequencies of the dephasing spectrum. This allows sampling of the diffusion spectrum, the Fourier transform of the velocity correlation function (VCF). It has been shown that restriction and flow alter this function in ways that can be mathematically characterized, yielding quantitative information on restriction geometry and flow parameters. It is demonstrated that in many systems of interest, dispersion of velocity will produce a peak in the VCF spectrum near ω = 0, while restricted diffusion will manifest itself in the spectrum at higher frequencies. The method, therefore, may be useful for decoupling their effects on the apparent diffusion coefficient (ADC), as well as in revealing the physics of both phenomena. This method has been implemented in model systems of packed beads, yielding data consistent with theoretical models of restricted diffusion spectra and data from one previous study [1]. The method may have significant application to biology and medicine, as well as the study of transport phenomena in porous media and complex flow.

Stress is ubiquitous. It creates mental and physical symptoms, causes problems at home and at work, and is a major factor in absenteeism and resignations. Nurses are challenged to create a healing environment for their patients while facing significant stressors of their own. A variety of strategies are available for coping with both job-connected stress and stress at home. For nurses to provide patients with the best available care, they, themselves, must feel cared for on a consistent basis. In spite of its scarcity, time devoted to "destressing " is definitely well spent.

Approximately 60 million Americans survive injuries sustained after a trauma event. Managing secondary problems is the responsibility for all health care professionals. Alteration in integumentary status, circulation, pulmonary issues, musculoskeletal involvement, and depression are the most prevalent problems that interdisciplinary health care professionals on the rehabilitation team must manage. Rehabilitation must begin at the time of the traumatic event. Benefits of injury prevention and early rehabilitation are explored.

This panel session focuses on utilization of Java for numeric-intensive applications, including the advantages and disadvantages of Java for future use with industrial independent software vendor (ISV)-based finite element methods (FEM) codes. Discussion will address both partial use of Java and/or complete code implementation; activities in this area are already in progress and have been reported by the Java Grande Forum (see http://www.javagrande.org). Some of the issues that will be discussed by the panelists and audience include: performance comparisons of Java, Fortran, C, and C++; primary deficiencies of Java with respect to future development of competitive commercial ISV-based FEM codes; Java standardization bottlenecks; strategies for transitioning to Java from existing large legacy commercial codes; current and future numeric-intensive benchmarks; actions to improve Java floating-point performance. This session is represented by biographical sketches of the panel participants, their individual reflections on the panel theme, and a list of related Internet references.

Various vertebrate and invertebrate traces and plants remains have been discovered in the Permian of Pico Paraes (Cantabrian Mountains). They occur in the Sagra Formation, a 400 m thick unit consisting of a vertical alternation of channels with conglomeratic sandstones and fossiliferous red siltstones with a caliche horizon at the top. The most common trace is Hyloidichnus major which is attributed to approximately 50 cm long Captorhinomorphs. Other tracks provisionally assigned to Limnopus could also indicate the presence of Temnospondyls. The bedding planes with traces also show some tracks of Isopodichnus cf. minutus which is ascribed to small triopsid crustaceans. Like the footprints, these are sometimes cut off by insect burrows like cf. Steinichnus, Scoyenia gracilis, Ancorichnus sp. or Skolithos . These fossiliferous levels have also yielded conchostracans, unidentifiable plant stems and a rather well-preserved frond of Supaia sp. The fossil association and sedimentological features suggest that the Sagra Formation is a floodplain deposit; the water depth was limited and fluctuated. Longer drier intervals also occurred. The vegetation was meso-xerophilous. The occurrence of the ichnopopulation Hyloidichnus major and Supaia in the Permian of France (Lodeve basin) and North America (Grand Canyon, U.S. A) suggests that the Sagra Formation can be correlated with the Rabejac Formation of the Lodeve basin. Based on comparisons with the Supaia -bearing Hertmit Shale, the Sagra Formation might be dated as early Leonardian, or even Artinskian when the Leonardian can indeed correlated with the Artinskian + Kungurian.

It has been widely suggested, but rarely demonstrated, that virtual environments (VEs) are effective training media. The purpose of this investigation was to evaluate how well a VE model of a complex office building trained individuals to navigate in the actual building. Sixty participants studied route directions and landmark photographs, then rehearsed the route using either the VE model, the actual building, or verbal directions and photographs. The VE model was presented in real time via a head-tracked display. Half of the participants in each rehearsal group also studied route maps. Everyone's route knowledge was then measured in the actual building. Building configuration knowledge was also measured. VE rehearsal produced more route knowledge than verbal rehearsal, but less than with rehearsal in the actual building. Type of rehearsal had no effect on configuration knowledge. Map study influenced neither route nor configuration knowledge. These results suggest that VEs that adequately represent real world complexity can be effective training media for learning complex routes in buildings, and should be considered whenever the real world site is unavailable for training.

Irradiation has been successful in the attenuation of infective stage parasites for use as vaccines against a number of parasites including Fasciola spp. The mechanisms of action of irradiation-attenuated vaccines, however, are not clearly understood. In this study, we examined the effect of 3, 10, and 40 krad of gamma-irradiation on the expression of carbohydrates and cathepsin-B by newly excysted juvenile Fasciola hepatica (NEJ). Following irradiation of metacercariae, the expression of concanavalin A (ConA)-specific sugars was decreased on the surface of NEJ and the expression of wheat germ agglutinin (WGA)-specific sugars was increased in the gut and reduced on the surface of NEJ. Cathepsin proteases are a major component of liver fluke excretory/secretory material (ES) and can cleave host immunoglobulin (Ig). Cathepsin-B protease was localized in nonirradiated NEJ to the gut lumen and to secretory granules within the gut epithelia. Irradiation of fluke with 3, 10, and 40 krad of gamma-rays significantly reduced the tissue expression of cathepsin-B at 8 hr postirradiation in an apparently dose-dependent manner. After a further 24 hr culture tissue expression of cathepsin-B was significantly reduced in 10- and 40-krad-irradiated NEJ. Protease activity of ES samples collected over a 24-hr period from irradiated and nonirradiated NEJ cultured in vitro were tested using a rabbit Ig cleavage assay. The proteolytic activity of ES from 10- and 40-krad-irradiated NEJ was reduced during the initial 6 hr in culture and between 12 and 24 hr when compared to ES from nonirradiated controls. Biosynthetic labeling experiments using [35S]methionine and [35S]cysteine indicated that ES material was actively synthesised during 48 hr in vitro culture. Therefore, from this study, we conclude that gamma-irradiation of NEJ alters expression of cathepsin-B protease and WGA- and ConA-specific sugars which may be detrimental to parasite invasion and contribute to the protective immune responses generated in the host by irradiation-attenuated metacercariae of Fasciola spp.

A low molecular mass monomeric protein termed Fh-KTM (Fasciola hepatica Kunitz-type molecule) was isolated from the trematode Fasciola hepatica. Fh-KTM is a single polypeptide of 58 amino acids and a Mr of 6751. The complete amino acid sequence of Fh-KTM was determined and revealed significant similarity to the Kunitz-type (BPTI) family of proteinase inhibitors. Several polymorphisms were observed suggesting that more than one Fh-KTM molecule may be expressed by this parasite. Modified proline residues were shown to occur at all four positions in this protein as 3-hydroxy derivatives. This is the first report of 3-hydroxyproline residues in a Kunitz-type molecule. Indirect immunofluorescence and immunogold labelling revealed that Fh-KTM is an abundant molecule within the parasite localised to the gut, the parenchymal tissue and the tegument of adult F. hepatica. Serine protease inhibition assays revealed that Fh-KTM exhibited little or no inhibition against chymotrypsin, kallikrein, urokinase or key serine proteases of the blood coagulation pathways. However, Fh-KTM was able to inhibit trypsin even though the P1 reactive amino acid of Fh-KTM was a leucine residue.

Melicope stipitata has yielded six acetophenone derivatives; acronylin, evodionol methyl ether, evodionol and three novel compounds. The latter were identified as 5-acetyl-6-hydroxy-2-(2-hydroxyisopropyl)-4-methoxybenzofuran (furostipitol), (rel)-(±)-6-acetyl-3,4-dihydro-4α-ethoxy-3β-hydroxy-5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran (3-hydroxydihydropyranostipitol-4-ethyl ether) and (rel)-(±)-6-acetyl-3,4-dihydro-3β,4α-dihydroxy-5,7-dimethoxy-2,2-dimethyl-2H-1-benzopyran (3,4-dihydroxydihydropyranostipitol). 5-Acetyl-6-hydroxy-2-(2-hydroxyisopropyl)-4-methoxybenzofuran was isolated together with a small quantity of another compound, tentatively identified as its dihydrofuran analogue, namely, 5-acetyl-2,3-dihydro-6-hydroxy-2-(2-hydroxyisopropyl)-4-methoxy benzofuran. The 1 H NMR spectra of 3,4-dihydroxydihydropyranostipitol in different solvents is discussed. In addition, the furocoumarins, bergapten, phellopterin, isoimperatorin andisopimpinellin, the angular pyranocoumarin, seselin, the 8-prenylated coumarins, osthol, peroxyauraptenol and osthenon, the biscoumarin, phebalin, the lignan, sesamin, and the triterpene, isobaurenol, were obtained.

In addition to the previously reported brombyin-I and brombyin-II, four further novel brombyin type derivatives have been obtained from the stem bark of Brombya platynema . These were identified as ( rel )-3β-piperonyl-4β-acetyl-3,4,4aβ,5,6,7,8,8aα-octahydronaphthal-1-ene (brombyin-III), ( rel )-3-piperonyl-4β-acetyl-1,4,4aβ,5,6,7,8,8aα-octahydronaphthal-2-en-1-one (brombyin-IV), 1-piperonyldodecan-9-ol-11 one (brombyin-V) and ( rel )-3β-piperonyl-4β-acetyl-2,3,4,4aβ,5,6,7,8-octahydronaphthalen-1(8a)-en-2α-ol (brombyin-VI). Also present were the simple cinnamic acid derivatives ( E )-piperonylprop-2-enal and ( E )-piperonylprop-2-enoic acid. A possible route for the formation of the brombyins is discussed.

We reviewed all new patients referred for treatment to the Sarcoma Unit at the Royal Marsden Hospital with a clinical diagnosis of soft tissue sarcoma (STS) during the course of 1 year (1989-1990). Of 118 patients, 65 (55.1%) had primary STS, 26 (22.0%) had recurrent STS, 19 (16.1%) had benign soft tissue tumours and eight (6.8%) had malignant tumours other than STS involving soft tissues and presenting clinically as soft tissue tumours. All patients underwent CT scanning which was used to assist diagnosis, assess operability or for radiotherapy planning. The CT findings of the benign lesions, all clinically suspicious of sarcoma, are discussed. The role of CT in the identification and management of these cases is emphasized.

The yeast gene encoding the 95-kDa subunit of the class III gene transcription factor TFIIIC was cloned. This gene, termed TFC1 (transcription factor C, gene 1), was isolated by screening a lambda gt11 yeast cDNA expression library using a polyclonal antiserum preparation which was previously shown to specifically recognize the 95-kDa subunit of yeast TFIIIC (Parsons, M. C., and Weil, P. A. (1990) J. Biol. Chem. 265, 5095-5103). TFC1 was found to be a single copy gene which contained a continuous open reading frame about 2 kilobases in length. TFC1 was shown to encode the 95-kDa subunit of TFIIIC by several criteria. Like the authentic yeast protein, the protein encoded by TFC1 had an apparent molecular weight of 95,000. In addition, the protein encoded by the TFC1 gene bound to the same antibody species as the yeast 95-kDa subunit of TFIIIC. Last, the sizes of the cleavage products of the Escherichia coli-expressed protein were indistinguishable from those of the cleavage products of the bona fide yeast 95-kDa protein.

In order to assess the value of computed tomographic scanning of the axilla and brachial plexus in the management of patients with arm symptoms following treatment for breast cancer, the case notes and diagnostic films of 102 such patients who underwent scanning between 1985 and 1990 at this institution were analysed retrospectively. The clinical indications for requesting computed tomography (CT) of the brachial plexus and axilla included arm oedema (52 patients, 51%), brachial plexus neuropathy (73 patients, 72%), and/or the presence of a palpable axillary mass (18 patients, 18%). Of 102 CT scans, 80 showed either no abnormality (31 patients, 30%), or axillary fibrosis (49 patients, 48%), and 22 (21%) showed radiological evidence of recurrent tumour. Only 4 of 84 patients with no palpable mass had computed tomographic evidence of occult recurrent tumour; all of these had concurrent evidence of distant metastatic disease (lung, liver, bone). Patients have been followed up for from between 1 and 15 years from diagnosis (median 5.5 years). The extremely low yield of tumour recurrence on computed tomographic scanning in the absence of a palpable axillary mass (4/84 patients, 5%; 95% CI 1–12), cannot justify CT as a method of screening for clinically occult axillary relapse in patients with arm symptoms following axillary surgery and radiotherapy for breast cancer. Computed tomographic scanning in these patients should only be employed to confirm the clinical suspicion of tumour as a baseline prior to further treatment.

We have studied seven patients presenting to the Royal Marsden Hospital between 1983 and 1989 with metastatic immature teratoma of the ovary. All patients underwent initial surgery followed by combination chemotherapy and a second laparotomy. Serial CT scans were performed at 2-3 monthly intervals from diagnosis until the second laparotomy, and the results of this were correlated with the CT appearances. In six of the seven patients CT scanning demonstrated 'retroconversion' of immature malignant tumour masses to benign mature disease during treatment. CT features of maturation included increased density of mass lesions, whose margins became better circumscribed in relation to adjacent tissues, and the onset of internal calcification, with fatty areas and cystic change. These changes on CT correlated exactly with normalization of an initially raised serum tumour marker, alpha feto-protein (AFP) in all six patients. The second laparotomy revealed only mature teratoma in all patients following chemotherapy. In three patients show continued growth of the mature deposits necessitated further surgery for local pressure symptoms, but overall, none has shown malignant relapse, and all are currently well between 1 and 6 years after diagnosis. This is the first report of the CT appearances of retroconversion of immature ovarian teratoma in a series of patients, which is an important radiological diagnosis to make in order to avoid confusion with advancing malignancy. A review of the literature is presented.

The class III gene transcription factor termed TFIIIC has been extensively purified from Saccharomyces cerevisiae. Three polypeptides of 138, 131, and 95 kDa consistently copurified with TFIIIC transcription factor activity. These polypeptides were present in approximately equimolar quantities in all TFIIIC preparations. To determine which, if any, of these polypeptides were involved in TFIIIC activity, rabbit polyclonal antibodies were generated against each of these three polypeptides purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoblot analyses showed that each of the three antiserum preparations reacted uniquely with the respective polypeptide to which they had been elicited. This lack of cross-reactivity by any of the antiserum preparations suggested that these three polypeptides represented distinct unrelated gene products. Each of the three specific antiserum preparations decreased the mobility of TFIIIC-tDNA complexes in a DNA mobility shift assay. More importantly, all three antiserum preparations directly inhibited the transcription factor activity of TFIIIC. In addition, all three antiserum preparations depleted a solution of TFIIIC transcription factor activity. These results indicated that each of these three polypeptides of Mr = 138,000, 131,000, and 95,000 was a distinct and necessary component of yeast TFIIIC. Immunoblot analyses of immunoaffinity-purified TFIIIC fractions indicated that each of the three antiserum preparations alone could deplete the solution of all three polypeptides. These results suggested that these three polypeptides were tightly associated with one another in solution.

Background Kaposi’s sarcoma-associated herpesvirus (KSHV) is the aetiological agent of Kaposi’s sarcoma, which preferentially arise in patients with AIDS. Although the introduction of combined antiretroviral therapy (cART) has dramatically reduced the incidence of Kaposi’s sarcoma, it remains a significant burden of morbidity and mortality in patients with AIDS. KSHV infection is necessary, but not sufficient to cause Kaposi’s sarcoma, indicating that microenvironmental factors are also required. Human endogenous retrovirus sequences (HERVs) constitute up to 8% of human genome and have resided in human genome for several million years. Interestingly, not all HERVs remain silent passengers; some, especially the HERV type K (HERV-K), have been found to be transactivated frequently in a variety of inflammatory diseases and human cancers. The HERV-K NP9 protein has been shown to be exclusively present in some tumours and has the oncogenic functions via regulating multiple signalling pathways. However, the role of HERV-K NP9 transactivation in viral oncogenesis, in particular in Kaposi’s sarcoma, and the potential value as a therapeutic target remain unknown. Methods We investigated the interaction between KSHV and HERV-K NP9. Findings We found that KSHV de novo infection or ectopic expression of KSHV-encoded Latency-associated Nuclear Antigen (LANA) protein transactivate HERV-K NP9 from human primary endothelial cells (the major cellular components within Kaposi’s sarcoma). We noted a higher level of HERV-K transactivation in peripheral blood mononuclear cells (PBMCs) from our cohort of HIV-positive/KSHV-positive patients than those from HIV-positive/KSHV-negative patients. Abundant NP9 expression was noted in Kaposi’s sarcoma tissue collected from HIV-positive patients. Further data indicate that the transactivation of NP9 is responsible for cell invasiveness and anchorage-independent growth of KSHV-infected endothelial cells. Interpretation Our data provide insights into the contribution of HERV-K NP9 transactivation to KSHV pathogenesis and tumorigenesis, and provide the framework for developing novel strategies targeting NP9 transactivation for improved treatment and/or prevention of Kaposi’s sarcoma in high-risk HIV-positive patients.

The accuracy of computed tomography (CT) in the assessment of nodal metastases was correlated retrospectively with the pathological examination in 28 patients with known head and neck squamous cell carcinoma, who underwent neck dissections. Three patients had bilateral neck dissections resulting in a total of 31 dissections. CT scanning correctly staged 28 of 31 neck dissections providing an accuracy of 90%, a sensitivity of 87.5% and a specificity of 100% in the detection of nodal metastases. Of the 21 true positives, underestimation of the extent of nodal disease occurred in seven cases. Regarding extracapsular nodal spread, CT resulted in an accuracy of 62%, a sensitivity of 62.5% and a specificity of 60%. All three false negatives for nodal metastases occurred in metastatic spread to the submandibular nodes. The existing criteria for assessment of nodal metastases with CT are sensitive and specific, but in the assessment of extrandal spread CT may not detect 37.5% of cases.

Two novel and related seco ring-A triterpene acids have been isolated from the oleoresin of Dacryodes normandii and identified as 21-oxo-3,4- seco -olean-4(23),12-dien-3-oic acid, and 21-oxo-3,4- seco -ursan-4(23),12-dien-3-oic acid.