Search

The management of high-risk prostate cancer has become increasingly sophisticated, with refinements in radical therapy and the inclusion of adjuvant local and systemic therapies. Despite this, high-risk prostate cancer continues to have significant treatment failure rates, with progression to metastasis, castrate resistance and ultimately disease-specific death. In an effort to discuss the challenges in this field, the UK National Clinical Research Institute’s Prostate Cancer Clinical Studies localised subgroup convened a multidisciplinary national meeting in the autumn of 2014. The remit of the meeting was to debate and reach a consensus on the key clinical and research challenges in high-risk prostate cancer and to identify themes that the UK would be best placed to pursue to help improve outcomes. This report presents the outcome of those discussions and the key recommendations for future research in this highly heterogeneous disease entity.

Despite the extensive development of prostate cancer (PCa) risk models that are used for patient–clinician decision-making for PCa screening, their predictive accuracy is unknown. In a meta-analysis of six different risk prediction models, results show that models have the potential to increase the sensitivity of PSA screening to detect any PCa (44% versus 21%). Background Despite the extensive development of risk prediction models to aid patient decision-making on prostate screening, it is unknown whether these models could improve predictive accuracy of PSA testing to detect prostate cancer (PCa). The objective of this study was to perform a systematic review to identify PCa risk models and to assess the model's performance to predict PCa by conducting a meta-analysis. Design A systematic literature search of Medline was conducted to identify PCa predictive risk models that used at least two variables, of which one of the variables was prostate-specific antigen (PSA) level. Model performance (discrimination and calibration) was assessed. Prediction models validated in ≥5 study populations and reported area under the curve (AUC) for prediction of any or clinically significant PCa were eligible for meta-analysis. Summary AUC and 95% CIs were calculated using a random-effects model. Results The systematic review identified 127 unique PCa prediction models; however, only six models met study criteria for meta-analysis for predicting any PCa: Prostataclass, Finne, Karakiewcz Prostate Cancer Prevention Trial (PCPT), Chun, and the European Randomized Study of Screening for Prostate Cancer Risk Calculator 3 (ERSPC RC3). Summary AUC estimates show that PCPT does not differ from PSA testing (0.66) despite performing better in studies validating both PSA and PCPT. Predictive accuracy to discriminate PCa increases with Finne (AUC = 0.74), Karakiewcz (AUC = 0.74), Chun (AUC = 0.76) and ERSPC RC3 and Prostataclass have the highest discriminative value (AUC = 0.79), which is equivalent to doubling the sensitivity of PSA testing (44% versus 21%) without loss of specificity. The discriminative accuracy of PCPT to detect clinically significant PCa was AUC = 0.71. Calibration measures of the models were poorly reported. Conclusions Risk prediction models improve the predictive accuracy of PSA testing to detect PCa. Future developments in the use of PCa risk models should evaluate its clinical effectiveness in practice.

Efficiency of non-point source pollution control methods may be altered in future climate. This study investigated climate change impacts on sediment and nutrient transport, and efficiency of best management practices (BMPs), in the Upper Pearl River Watershed (UPRW) in Mississippi. The Soil and Water Assessment Tool was applied to the UPRW using observed flow, sediment and nutrient data. Water quality samples were collected at three US geological survey gauging stations. The model was successfully calibrated and validated for daily time steps (Nash Sutcliffe efficiency and coefficient of determination – R2 up to 0.7) using manual and automatic (sequential uncertainty fitting version 2) methods from February 2010 to May 2011. Future weather scenarios were simulated using the LARS-WG model, a stochastic weather generator, with Community Climate System Model, global climate model, which was developed by the National Center for Atmospheric Research in the USA. On the basis of the Special Report on Emissions Scenarios A1B, A2 and B1 of the Intergovernmental Panel on Climate Change, climate change scenarios were simulated for the mid (2046–2065) and late (2080–2099) century. Effectiveness of four BMPs (Riparian buffer, stream fencing, sub-surface manure applications and vegetative filter strips) on reducing sediment and nutrient were evaluated in current and future climate conditions. Results show that sediment, nitrogen and phosphorus loadings will be increased up to a maximum of 26.3%, 7.3% and 14.3%, respectively, in future climate conditions. Furthermore, the effectiveness of BMPs on sediment removal will be reduced in future climate conditions, and the efficiency of nitrogen removal will be increased, whereas phosphorus removal efficiency will remain unchanged. Copyright © 2013 John Wiley & Sons, Ltd.

Idiopathic muscular hypertrophy of the oesophagus (IMHO) is reported in equids as an incidental post mortem finding, infrequently associated with clinical signs of oesophageal dysfunction or additional oesophageal abnormalities. Clinicopathological and post mortem findings are presented from a 15-year-old gelding that developed a spontaneous perforation of the distal, intrathoracic oesophagus, in association with IMHO. The majority of oesophageal perforations documented in the equine literature have been related to external or iatrogenic trauma resulting in rupture of the cervical portion of the oesophagus. In this case, the early presenting features included pyrexia and inappetance, and progressed over a 4 day period to include signs of tachypnoea, tachycardia and endotoxaemia due to the development of a fatal septic pleuritis and pleural effusion. Oesophageal obstruction was not a presenting feature. Diagnostic investigation in cases of unexplained septic pleural effusion should include oesophageal endoscopic evaluation to rule out perforation of the intrathoracic oesophagus. IMHO may represent a clinically significant, primary disease entity with the potential to lead to oesophageal perforation.

The pH measurement of exhaled breath condensate (EBC) may provide a non-invasive method of assessing the lower airways of horses but the methodology used may influence findings. The aim of this study was to investigate the effect of two sampling devices and three methods of condensation surface cooling (ethanol slush, −100 °C; dry ice, −75 °C; water ice, 0 °C) on EBC pH. Each method was tested 30 times using six healthy ponies. Sample pH was determined before and after de-aeration with argon for 10 min. Sampler design was found to significantly affect pH. Samples collected as a liquid had a significantly higher pH than samples frozen during collection (P < 0.05). De-aeration resulted in significantly higher pH (P < 0.05) with less variation. This study has shown that device design and condensation surface temperature will influence EBC pH, which will prevent a direct comparison of results when different methodologies are used.

Drop-fill water management schemes for aquacultural ponds reduce both groundwater use and effluent release. A drop-fill scheme assumes that pond water level will be allowed to decrease to the “drop” depth before makeup water is used to return it to the “fill” depth, which is typically some fraction (e.g., 1/2) of the drop depth. This paper compares predicted performance of drop-fill schemes at five sites in the Southeast U.S. (Thompsons, TX, Stuttgart, AR, Stoneville, MS, Clemson, SC, and Fairhope, AL). The locations were chosen to assess the effect of the east–west precipitation gradient and the south–north change from maritime to continental characteristics on the drop-fill approach in this region. Performance of the drop-fill schemes was based on calculated daily water balances for ponds using 40-year (1961–2000) precipitation (P) and evaporation (E) records at the sites. Pond evaporation is assumed to be 0.8 × pan evaporation. Since performance differences based on regional P minus E (P−E) records was the subject of this work, ponds were assumed identical in other respects (i.e., all ponds were assumed to be levee-type and to have zero infiltration). Simulated drop-fill schemes tested included (in cm): 0/0, 5/2.5, 10/5, 15/7.5, 20/10, 25/12.5, 30/15, 45/22.5, 60/30, 90/45, and 120/60. Each scheme was simulated using daily time steps for 40 years at each site. Results suggested that rigorous adherence to even a modest drop-fill scheme results in substantial reductions in both groundwater use and effluent release. It also appears that P−E conditions at all sites allow implementation of more aggressive drop-fill schemes in properly designed ponds that will require no supplemental groundwater for most years. This was also true with respect to effluent release at three of five sites. At two sites, precipitation was sufficiently large that zero effluent years were either not predicted (Fairhope) or relatively uncommon (Clemson) for any drop-fill scheme.

Data collected from 45 commercial channel catfish, Ictalurus punctatus , ponds were used to develop empirical models predicting sediment oxygen demand (SOD). Seven acceptable models were combined with a Monte-Carlo sampling distribution to predict industry-wide sediment oxygen demand (SOD i ). The SOD i values obtained from the best equation were used in simulations to assess the effect of diurnally varying water column dissolved oxygen (DO) concentrations on SOD and the effect of pond water depth on the contribution of SOD to overall pond respiration. Estimated SOD i ranged from 62 to 962 mg m −2 h −1 , with a mean of 478 mg m −2 h −1 . There was a 95% probability of mean SOD i being ≥700 mg m −2 h −1 . The effects of diurnal variation in DO concentration in the water column on expression of SOD was modeled by combining maximum SOD i , an empirical relationship between DO and SOD, and simulated pond DO concentrations. At DO concentrations >15 mg l −1 , diel SOD in catfish ponds exceeded 20 g O 2 m −2 day −1 . But when average diel DO was −1 and the range of DO concentration was 6–8 mg l −1 , SOD decreased to 13 g O 2 m −2 day −1 because DO availability limited the full expression of potential SOD. Respiration totals for sediment (average SOD i ), plankton, and fish respiration were calculated for pond water depths ranging from 0.25 to 4 m. Although whole-pond respiration increases as pond depth increases, the proportion of total respiration represented by sediment decreased from 48 to 10% by increasing water depth over this range. The results of these studies show that SOD is a major component of total pond respiration and that certain management practices can affect the impact of SOD on pond oxygen budgets. Mixing ponds during daylight hours, either mechanically or by orienting ponds for maximum wind fetch, will increase oxygen supply to sediments, thereby allowing maximum expression of SOD and maximum mineralization of sediment organic matter. Given a mixed condition caused by wind or other artificial means, the construction of deeper ponds increases the total mass of DO available for all respiration, causing nighttime DO concentrations to decline at a slower rate, reducing the need for supplemental aeration. Because a pond’s water volume decreases over time from sediment accumulation, annual aeration costs will increase with pond age. Constructing ponds with greater initial depth will therefore reduce long-term cost of aeration, allow more flexible management of pond water budget, and reduce the long-term expense associated with pond reconstruction.

This paper develops a methodology for identifying, classifying, and implementing a set of best practices that can increase the quality, reliability, and timeliness of industries that provide maintenance, repair, and overhaul (MRO) services on products. By cataloging and documenting these best “sustainment” practices, one can learn from others' attempts to maintain systems and avoid non‐value‐added processes. The authors identify the knowledge that exists at various research centers and MRO providers at US corporations – wherever the best practices may reside. The paper specifically focuses on the sustainment of US military systems, but it also draws analogies and conclusions for other global product and service providers.

The horse, and the complexly diverse and international equine industry of which it is the foundation, are under constant threat from a variety of viral diseases (Table 1), which not only has a significant impact on animal welfare throughout the world, but also maintains a persistent economic burden on the industry. In the 21st century, where international transportation of horses for competition, sale and breeding is commonplace, and in a rapidly changing environment that is breaking down barriers for the geographical confinement of infectious agents, the role of the equine veterinary practitioner in the control of viral disease is also changing. The identification and diagnosis of any infectious disease must not only serve as the basis for appropriate therapeutic intervention at the individual or group level, but must also be considered an imperative step for appropriate disease control, quarantine and prevention, and for national disease surveillance. In order to achieve these measures, however, practitioners must have at their disposal readily accessible, reliable and affordable diagnostic tests that can provide results within a time frame that is both compliant with the demands of daily practice and allows prompt and appropriate intervention.

I have no key message to add because this is a reply to a letter to the editor with no new message.

BACKGROUND Laparoscopic inguinal hernia repair is a well described technique. However, mesh fixation with staples has been implicated as a cause of chronic groin pain. Recent studies have shown low rates of postoperative pain and hernia recurrence when using a self-adhesive mesh such as Parietex ProGripTM (Covidien, Dublin, Ireland). Owing to the adhesive nature of the mesh, manoeuvring it into the correct position can be challenging as it adheres to the tissue firmly. We describe a technique that allows easy positioning of the mesh, saving operative time and the use of staple fixation devices.

A management strategy designed to reduce the volume of effluent discharged from catfish ponds and decrease dependence upon groundwater was tested using a mathematical model. The approach is predicated upon the simultaneous use of certain ponds for fish production and rainwater storage. Production/storage ponds are deeper than conventional production ponds and receive overflow during rain events from other production ponds that are linked in a two- or four-pond series. The model which simulated system performance used a 26-year record of precipitation and evaporation and was based upon a computed water balance for the linked pond system. Based upon simulations representing multiple scenarios, model predictions suggested that effluent discharge may be reduced by 40–90% and groundwater use may be reduced by 40–75%. This management approach, if implemented, may be a viable method to reduce nutrient loading of receiving waters and conserve groundwater.

Objectifs L’imagerie par Cerenkov Luminescence (CLI), basee sur l’imagerie optique de traceurs radioactifs, permet de determiner, en peroperatoire, le statut ganglionnaire et les marges chirurgicales sur une piece d’exerese. Ainsi, l’etude PRostate Imaging for Margin Evaluation (PRIME) est en cours pour evaluer la faisabilite et la securite de l’utilisation de la 18F-choline CLI dans la chirurgie du cancer de prostate. Methodes L’etude PRIME a inclus 3 patients avec un cancer de prostate a haut risque, programmes pour une prostatectomie radicale cœlioscopique robot-assistee. Apres injection intraveineuse de 370 MBq (± 10 %) de 18F-choline, les pieces de prostatectomies et de lymphadenectomies ont ete analysees par un CLI specimen-analyser (Lightpoint Medical Ltd, Royaume-Uni) juste apres excision (temps d’acquisition 300 secondes, matrix 512 × 512). Pour chaque region d’interet, la radiance corrigee (ph/s/cm2/str/MBq) a ete calculee et nous reportons le ratio de radiance entre la tumeur et le tissu sain (tumour-to-background ratio [TBR]). Les doses de radioactivite (μSv) recues par l’equipe chirurgicale ont ete mesurees a l’aide de badges-dosimetres. Resultats Les images CLI peroperatoires des 3 prostatectomies ont montre une radiance elevee avec un TBR de 3,45, 4,90 et 2,49 respectivement pour chaque patient. Pour 2 prostatectomies avec cancer de haut-grade, les analyses CLI et histologiques etaient correlees, mais la troisieme piece, histologiquement de bas-grade, etait discordante. Les pieces de lymphadenectomies obtenues etaient negatives aussi bien en analyse CLI qu’en histologie. Le protocole CLI n’a genere ni temps additionnel de chirurgie ni complications peroperatoires specifiques. Selon la duree de la procedure et la proximite avec le patient, la dose de radiation maximale recue etaient de 110–180 μSv et 40–80 μSv respectivement pour l’interne et la panseuse. Pour favoriser la decroissance radioactive, des precautions complementaires ont ete prises pour l’environnement chirurgical et les pieces operatoires. Conclusion L’analyse peroperatoire de pieces d’exerese par 18 F-choline CLI est une procedure faisable et fiable. Les premiers resultats obtenus dans la chirurgie du cancer de prostate sont encourageants. La sensibilite en profondeur de l’analyse des tissus par CLI etant de quelques millimetres, d’autres developpements sont necessaires pour reduire le signal obtenu a la definition histologique des marges chirurgicales ( Fig. 1 ).

A best evidence topic in surgery was written according to a structured protocol. The question addressed how subintimal angioplasty (SIA) compares to transluminal angioplasty (TA) for the treatment of femoral occlusive disease. One hundred and thirty two papers were found using the reported search; the 5 which represented the best evidence to answer the question are discussed. The evidence on this subject is limited; there are no randomised controlled trials (RCTs) comparing SIA to TA for pathologically equivalent lesions. However SIA remains a safe and effective alternative to surgical bypass grafting when TA cannot be performed.

Sediment oxygen demand (SOD) was measured in catfish aquaculture ponds using a computer-controlled data acquisition system coupled with in situ respirometers. A total of 86 rate determinations were made in northwest Mississippi. Calculated SOD rates averaged 4·44 g/m 2 per day at an average temperature of 29°C. These rates exceeded those recorded previously in catfish ponds and may have reflected differences in pond construction and management. Location within the pond, but neither age nor location-age interaction, appeared to affect SOD.

Analyses of exhaled breath (EB) and exhaled breath condensate (EBC) are non-invasive modalities for assessing the lower airways but these methods have not been applied to Thoroughbred racehorses in training. The aims of this study were to determine whether EB and EBC could be obtained from Thoroughbred racehorses in the field and to investigate the effects of exercise per se and during different ambient temperatures and humidity on exhaled concentrations of nitric oxide (eNO), carbon monoxide (eCO) and EBC pH. EB and EBC samples were obtained from 28 Thoroughbred racehorses pre- and post-exercise during warm (n = 23) and/or cold (n = 19) ambient temperatures. eNO was detected in 19/84 EB samples. eCO was measured in 39/42 EB samples pre-exercise (median 1.3 ppm) and concentrations decreased significantly post-exercise (median 0.8 ppm, P < 0.005) and were associated with ambient temperature. EBC pH was 4.51 ± 0.23 pre-exercise and increased significantly post-exercise (4.79 ± 0.59, P = 0.003). The study documented the collection of EB and EBC from Thoroughbred racehorses in a field setting. Alterations in concentrations of volatile gases and EBC pH occurred in response to exercise, and were likely to have been influenced by environmental factors.

The analysis of biomarkers in exhaled breath (EB) and exhaled breath condensate (EBC) may allow non-invasive and repeatable assessment of respiratory health and disease in mammals. Compared to human medicine, however, research data from EB and EBC analysis in veterinary medicine are limited and more patient variables influencing concentrations of EB/EBC analytes may be present. In addition, variations in methodologies between studies may influence results. A comparison of the approaches used in veterinary research by different groups may aid in the identification of potentially reliable and repeatable biomarkers suitable for further investigation. To date, changes in acid–base status and increased concentrations of inflammatory mediators have been the main findings in studies of pulmonary disease states in animals. Whilst these biomarkers are unlikely to represent specific and sensitive diagnostic parameters, they do have potential application in monitoring disease progression and treatment response.

Stalker (AIAA Paper 87-0403) has suggested that, by ejecting molecules directly upstream from the entire face of a satellite, it is possible to reduce the drag on a satellite in low-Earth orbit and hence maintain orbit with a total fuel mass (for forward ejection and conventional reaction rockets) less than the typical mass requirements of conventional rockets. An analytical analysis is presented here, as well as Monte Carlo simulations. These indicate that to reduce the overall drag on the satellite significantly, collisions between the freestream and ejected molecules must occur at least two satellite diameters upstream. This can be achieved if the molecules are ejected far upstream from the satellite’s surface through a sting that projects forward from the satellite. Using some estimates of what would be feasible sting arrangements, we find that the drag on the satellite can be reduced to such an extent that the satellite’s orbit can be maintained with a total fuel mass of less than 60% of that required for reaction rockets alone. Upstream ejection is effective in reducing the drag for freestream Knudsen numbers less than approximately 250, but not otherwise.

H. Smidt in a recent note on the reduction of methylene blue by means of milk confirmed the results of Schardinger that a mixture of formaldehyde and methylene blue is decolorised by the action of milk. This reaction depends on the presence of a ferment—a catalase—in the milk, and, as this ferment is readily destroyed by heat, serves as a very simple method of determining whether a given sample of milk is “raw” or not. By way of conclusion Smidt stated that he thought this test might be of still further utility in that it might be possible to estimate the degree of bacterial contamination of the milk by its means. If such a comparatively simple test could be employed, in an easy and effective fashion, it would be of immense service, as, owing to the rapidity with which it can be carried out, the milk could be examined before distribution.

In the samples of “blown” preserve tins examined by me, organisms of an intestinal type were present, which on reinoculation into sound tins gave rise to a gaseous decomposition.No toxic symptoms were produced on feeding guinea-pigs with the contents of the “blown” tins.

Tests were conducted to determine the effectiveness of calcium sulfate, calcium chloride, calcium carbonate, acetic acid, and ground corn for the control of high pond pH. The tests were conducted in 24 9400 liter pools. Salts of calcium did not significantly reduce daily maximum pH relative to control pools, although mean pH levels were consistently less than control values at higher application concentrations. Acetic acid did not effectively control pH at the level tested. Application of ground corn did significantly reduce pH at all levels tested. Use of ground corn has become a routine management strategy for pH control in shrimp ponds at Mississippi State University.

An electro-optical counter was designed to count postlarval prawns, Macrobrachium rosenbergii. Counts were made by the detection of white light scattered by the passage of prawns through the counter. Tests were conducted to determine the effect of detector angle, sensor threshold voltage, and counting-tube diameter on the counting process. Counting errors were found to be approximately 7% at a counting rate of 50!min.

A model for predicting the vertical temperature profile of turbid freshwater ponds is described. High resolution in space and time and a reduction in the number of meteorological inputs usually required by such models is achieved by using pond surface temperature as a model input. A method to estimate hourly surface temperature is proposed and demonstrated.

It has been known from antiquity that involution of the uterus is aided by putting the child to the breast, and the work of Moir (1933) has demonstrated conclusively that suckling brings about waves of contraction of the puerperal uterus. Since suckling must necessarily involve stimulation of the nipple, it seemed of interest to know what sensory apparatus is present in the nipple to receive these stimuli. While histological studies of the mammary gland itself have been numerous, only slight attention has been paid to the histological structure of the areola and the nipple.It must be appreciated from the outset that the present study is devoted to the innervation of the nipple in the quiescent breast. There may be considerable change during pregnancy and lactation, not only in the size of the organ and its epithelium but also in the other structures. It has been shown that there is an increase in the number of nerve-fibres in the actively secreting mammary tissue, and it is possible that there is an increase in the nerve-structures of the nipple also. The richness of the innervation in the quiescent nipple certainly makes a further study of these nerve-structures during pregnancy and lactation of great interest.

Mr. President, Ladies and Gentlemen,—Probably most of what I shall say to you this afternoon will be well known to you; indeed, many of you may think the information self-evident and trivial, but in spite of this I hope that what I say may serve to re-emphasise in your minds the fact that we are all very subject to our environment.