Limits and possibilities of surgical treatment of locally advanced prostatic carcinoma

Prostatic carcinoma is the second most diagnosed malignant tumor in the Netherlands, only carcinoma of the lung is more frequent. In 1991 4343 men were diagnosed with prostate cancer, making up 14.1% of all diagnosed malignant tumors. In the age-group 60-74 years the incidence was second after pulmonary carcinoma, and in the age-group >75 years it is the most frequently diagnosed malignancy. In 1991 2108 patients died because of prostate cancer. The mortality/incidence ratio is 0,49; which means that about 50% of the patients will die because of their prostatic malignancy. The incidence of prostatic cancer in developed countries is rising. Lu-Yao reported an increase in the incidence-rates of prostatic cancer in the United States of America of6.4% per year between 1983 and 1989'. This increase appeared to be due to the detection of early-stage disease, but there was no increase in the incidence-rate of metastatic cancer. There was no increase in mortality rates during this study-period. In the Netherlands 3% of all mortality among men was due to prostate cancer (1989) 3. In 1994 van der Gulden reported on the trends in mortality-rates for patients with prostate cancer in the Netherlands'. The age-adjusted mortality-rates rose between 1950 and 1989 with an average increase of 1 % per year. A continuous increase of mortality from prostate cancer was found in consecutive birth-cohorts (defined by combining age and calender-time periods on the basis of their central year of birth). There was a steep rise in the mortality from prostate cancer with age; for the age-category 55-59 years the prostate cancer mortality-rate was 11.2 per 100.000 man-years, but for the category >85 years this was 921.8. This rise in the incidence and mortality of prostate cancer points out that this disease will become more and more important in the years to come. Since more cancers tend to be localized, the role of radical prostatectomy in the treatment of prostatic carcinoma will become even more important than it is today

Analysis of the mechanical behaviour of a 11.5 T Nb3Sn LHC dipole magnet according to the ring collar concept

According to the CERN-LHC (Large Hadron Collider) reference design, 10-tesla twin-aperture NbTi dipoles will be built with split collars that enclose both apertures. As part of the development program towards an experimental 11.5-tesla Nb3Sn LHC dipole magnet, the mechanical implications of an alternative collar concept have been studied with a finite element analysis. In this concept ring shaped collars are shrunk on each finished single aperture coil, thus providing the necessary room-temperature prestress. This system results in a major improvement of the stress distribution in the collars. It is noted that introduction of friction at the sliding planes can cause reopening of the gap between the yoke halves during excitation. This depends strongly on the value of the friction coefficient

Development of an experimental 10 T Nb3Sn dipole magnet for the CERN LHC

An experimental 1-m long twill aperture dipole magnet developed using a high-current Nb3Sn conductor in order to attain a magnetic field well beyond 10 T at 4.2 K is described. The emphasis in this Nb3Sn project is on the highest possible field within the known Large Hadron Collider (LHC) twin-aperture configuration. A design target of 11.5 T was chosen

Amplified melt and flow of the Greenland ice sheet driven by late-summer cyclonic rainfall

Intense rainfall events significantly affect Alpine and Alaskan glaciers through enhanced melting, ice-flow acceleration and subglacial sediment erosion, yet their impact on the Greenland ice sheet has not been assessed. Here we present measurements of ice velocity, subglacial water pressure and meteorological variables from the western margin of the Greenland ice sheet during a week of warm, wet cyclonic weather in late August and early September 2011. We find that extreme surface runoff from melt and rainfall led to a widespread acceleration in ice flow that extended 140 km into the ice-sheet interior. We suggest that the late-season timing was critical in promoting rapid runoff across an extensive bare ice surface that overwhelmed a subglacial hydrological system in transition to a less-efficient winter mode. Reanalysis data reveal that similar cyclonic weather conditions prevailed across southern and western Greenland during this time, and we observe a corresponding ice-flow response at all land- and marine-terminating glaciers in these regions for which data are available. Given that the advection of warm, moist air masses and rainfall over Greenland is expected to become more frequent in the coming decades, our findings portend a previously unforeseen vulnerability of the Greenland ice sheet to climate change

TIPIT: A randomised controlled trial of thyroxine in preterm infants under 28 weeks' gestation

<p>Abstract</p> <p>Background</p> <p>Infants born at extreme prematurity (below 28 weeks' gestation) are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone which is recognised to be a frequent phenomenon in these infants. At present it is unclear whether low levels of thyroid hormone are a cause of disability, or a consequence of concurrent adversity.</p> <p>Methods</p> <p>We propose an explanatory multi-centre double blind randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks' corrected gestational age. The primary outcome will be brain growth. This will be assessed by the width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks' corrected gestational. The secondary outcomes will be (a) thyroid hormone concentrations measured at increasing postnatal age, (b) status of the hypothalamic pituitary axis, (c) auxological data between birth and 36 weeks' corrected gestational age, (d) thyroid gland volume, (e) volumes of brain structures (measured by magnetic resonance imaging), (f) determination of the extent of myelination and white matter integrity (measured by diffusion weighted MRI) and brain vessel morphology (measured by magnetic resonance angiography) at expected date of delivery and (g) markers of morbidity including duration of mechanical ventilation and chronic lung disease.</p> <p>We will also examine how activity of the hypothalamic-pituitary-adrenal axis modulates the effects of thyroid supplementation. This will contribute to decisions about which confounding variables to assess in large-scale studies.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN89493983</p

The Effect of the Visual Context in the Recognition of Symbolic Gestures

Background: To investigate, by means of fMRI, the influence of the visual environment in the process of symbolic gesture recognition. Emblems are semiotic gestures that use movements or hand postures to symbolically encode and communicate meaning, independently of language. They often require contextual information to be correctly understood. Until now, observation of symbolic gestures was studied against a blank background where the meaning and intentionality of the gesture was not fulfilled. Methodology/Principal Findings: Normal subjects were scanned while observing short videos of an individual performing symbolic gesture with or without the corresponding visual context and the context scenes without gestures. The comparison between gestures regardless of the context demonstrated increased activity in the inferior frontal gyrus, the superior parietal cortex and the temporoparietal junction in the right hemisphere and the precuneus and posterior cingulate bilaterally, while the comparison between context and gestures alone did not recruit any of these regions. Conclusions/Significance: These areas seem to be crucial for the inference of intentions in symbolic gestures observed in their natural context and represent an interrelated network formed by components of the putative human neuron mirro

Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.</p> <p>Methods/Design</p> <p>This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (¹²⁵I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with ¹²⁵I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during ¹²⁵I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.</p> <p>The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.</p> <p>Discussion</p> <p>To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.</p> <p>Trial registration</p> <p>UMIN000003992</p

Infrasound as a cue for seabird navigation

Seabirds are amongst the most mobile of all animal species and spend large amounts of their lives at sea. They cross vast areas of ocean that appear superficially featureless, and our understanding of the mechanisms that they use for navigation remains incomplete, especially in terms of available cues. In particular, several large-scale navigational tasks, such as homing across thousands of kilometers to breeding sites, are not fully explained by visual, olfactory or magnetic stimuli. Low-frequency inaudible sound, i.e., infrasound, is ubiquitous in the marine environment. The spatio-temporal consistency of some components of the infrasonic wavefield, and the sensitivity of certain bird species to infrasonic stimuli, suggests that infrasound may provide additional cues for seabirds to navigate, but this remains untested. Here, we propose a framework to explore the importance of infrasound for navigation. We present key concepts regarding the physics of infrasound and review the physiological mechanisms through which infrasound may be detected and used. Next, we propose three hypotheses detailing how seabirds could use information provided by different infrasound sources for navigation as an acoustic beacon, landmark, or gradient. Finally, we reflect on strengths and limitations of our proposed hypotheses, and discuss several directions for future work. In particular, we suggest that hypotheses may be best tested by combining conceptual models of navigation with empirical data on seabird movements and in-situ infrasound measurements

TIPIT: A randomised controlled trial of thyroxine in preterm infants under 28 weeks gestation: Magnetic Resonance Imaging and Magnetic Resonance Angiography protocol

<p>Abstract </p> <p>Background</p> <p>Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development. Further research in preterm infants using neuroimaging techniques will increase our understanding of the specificity of the effects of hypothyroxinaemia on the developing foetal brain. This is an explanatory double blinded randomised controlled trial which is aimed to assess the effect of thyroid hormone supplementation on brain size, key brain structures, extent of myelination, white matter integrity and vessel morphology, somatic growth and the hypothalamic-pituitary-adrenal axis.</p> <p>Methods</p> <p>The study is a multi-centred double blinded randomised controlled trial of thyroid hormone supplementation in babies born below 28 weeks' gestation. All infants will receive either levothyroxine or placebo until 32 weeks corrected gestational age. The primary outcomes will be width of the sub-arachnoid space measured using cranial ultrasound and head circumference at 36 weeks corrected gestational age. The secondary outcomes will be thyroid hormone concentrations, the hypothalamic pituitary axis status and auxological data between birth and expected date of delivery; thyroid gland volume, brain size, volumes of key brain structures, extent of myelination and brain vessel morphology at expected date of delivery and markers of morbidity which include duration of mechanical ventilation and/or oxygen requirement and chronic lung disease.</p> <p><b>Trial registration</b></p> <p>Current Controlled Trials ISRCTN89493983</p

The assessment and rehabilitation of prospective memory problems in people with neurological disorders: A review

People with neurological disorders often report difficulty with prospective memory (PM), that is, remembering to do things they had intended to do. This paper briefly reviews the literature regarding the neuropsychology of PM function, concluding that from the clinical perspective, PM is best considered in terms of its separable but interacting mnemonic and executive components. Next, the strengths and limitations in the current clinical assessment of PM, including the assessment of component processes, desktop analogues of PM tasks, and naturalistic PM tasks, are outlined. The evidence base for the rehabilitation of PM is then considered, focusing on retraining PM, using retrospective memory strategies, problem-solving training, and finally, electronic memory aids. It is proposed that further research should focus on establishing the predictive validity of PM assessment, and refining promising rehabilitation techniques