Dosimetric benefits and preclinical performance of steerable needles in HDR prostate brachytherapy.

Prostate cancer patients with an enlarged prostate and/or excessive pubic arch interference (PAI) are generally considered non-eligible for high-dose-rate (HDR) brachytherapy (BT). Steerable needles have been developed to make these patients eligible again. This study aims to validate the dosimetric impact and performance of steerable needles within the conventional clinical setting. HDR BT treatment plans were generated, needle implantations were performed in a prostate phantom, with prostate volume > 55 cm3 and excessive PAI of 10 mm, and pre- and post-implant dosimetry were compared considering the dosimetric constraints: prostate V100 > 95 % (13.50 Gy), urethra D0.1cm3 < 115 % (15.53 Gy) and rectum D1cm3 < 75 % (10.13 Gy). The inclusion of steerable needles resulted in a notable enhancement of the dose distribution and prostate V100 compared to treatment plans exclusively employing rigid needles to address PAI. Furthermore, the steerable needle plan demonstrated better agreement between pre- and post-implant dosimetry (prostate V100: 96.24 % vs. 93.74 %) compared to the rigid needle plans (79.13 % vs. 72.86 % and 87.70 % vs. 81.76 %), with no major changes in the clinical workflow and no changes in the clinical set-up. The steerable needle approach allows for more flexibility in needle positioning, ensuring a highly conformal dose distribution, and hence, HDR BT is a feasible treatment option again for prostate cancer patients with an enlarged prostate and/or excessive PAI.

Long-term Overall Survival after External Beam Radiotherapy for Localised Prostate Cancer.

AIMS: Knowledge on survival probabilities is essential for determining optimal treatment strategies. We studied overall survival and associated prognostic factors in Dutch patients with localised prostate cancer (PCa) selected for external beam radiotherapy. MATERIALS AND METHODS: For this single-centre retrospective cohort study, we identified all T1-T3 PCa patients (aged 55-80 years) in the radiotherapy planning database with a start date between January 2006 and December 2013, treated with 72-78 Gy in 2 Gy fractions to the prostate ± seminal vesicles (n = 1536). Long-term androgen deprivation therapy (ADT) was predominantly prescribed in the case of extracapsular disease (>T3). Overall survival was estimated using the Kaplan-Meier method. Prognostic factors were evaluated in Cox regression models for the intermediate-risk and high-risk groups. RESULTS: The median follow-up was 12 years for patients who were alive. Ten-year survival rates were 79.0% for low-risk (n = 120), 59.9% for intermediate-risk (n = 430) and 56.8% for high-risk patients (n = 986). A higher age, higher comorbidity score, active smoking and Gleason score ≥8 had a statistically significant negative impact on overall survival at multivariable analysis. ADT was associated with superior overall survival in the high-risk group translating into overall survival rates similar to the intermediate-risk group. CONCLUSIONS: Although PCa patients selected for external beam radiotherapy are typically in good health, their comorbidity score and smoking habits appeared to be dominant predictors for overall survival. Overall survival rates within the high-risk group varied, showing improved overall survival with ADT prescription and worse overall survival in the case of Gleason score ≥8.

Observation of Radar Echoes from High-Energy Particle Cascades.

We report the observation of radar echoes from the ionization trails of high-energy particle cascades. Data were taken at the SLAC National Accelerator Laboratory, where the full electron beam (∼10^{9} e^{-} at ∼10 GeV/e^{-}) was directed into a plastic target to simulate an ultrahigh-energy neutrino interaction. The target was interrogated with radio waves, and coherent radio reflections from the cascades were detected with properties consistent with theoretical expectations. This is the first definitive observation of radar echoes from high-energy particle cascades, which may lead to a viable neutrino detection technology for energies ≳10^{16} eV.

Likelihood analysis of supersymmetric SU(5) GUTs.

We perform a likelihood analysis of the constraints from accelerator experiments and astrophysical observations on supersymmetric (SUSY) models with SU(5) boundary conditions on soft SUSY-breaking parameters at the GUT scale. The parameter space of the models studied has seven parameters: a universal gaugino mass [Formula: see text], distinct masses for the scalar partners of matter fermions in five- and ten-dimensional representations of SU(5), [Formula: see text] and [Formula: see text], and for the [Formula: see text] and [Formula: see text] Higgs representations [Formula: see text] and [Formula: see text], a universal trilinear soft SUSY-breaking parameter [Formula: see text], and the ratio of Higgs vevs [Formula: see text]. In addition to previous constraints from direct sparticle searches, low-energy and flavour observables, we incorporate constraints based on preliminary results from 13 TeV LHC searches for jets + [Formula: see text] events and long-lived particles, as well as the latest PandaX-II and LUX searches for direct Dark Matter detection. In addition to previously identified mechanisms for bringing the supersymmetric relic density into the range allowed by cosmology, we identify a novel [Formula: see text] coannihilation mechanism that appears in the supersymmetric SU(5) GUT model and discuss the role of [Formula: see text] coannihilation. We find complementarity between the prospects for direct Dark Matter detection and SUSY searches at the LHC.

Recurrence rate of lentigo maligna after micrographically controlled staged surgical excision.

BACKGROUND: Lentigo maligna is a slowly growing melanoma in situ. Current guidelines advise wide local excision with a margin of 5 mm as the treatment of first choice, which has recurrence rates ranging from 6% to 20%. OBJECTIVES: To determine retrospectively the recurrence rate of lentigo maligna after staged surgical excision. METHODS: Records of all patients with lentigo maligna treated with our method of staged surgical excision between 2002 and 2011 were retrieved. To identify recurrences we used the computer program Sympathy, which is linked to PALGA, a nationwide network and registry of histo- and cytopathology in the Netherlands. RESULTS: We identified 100 patients, who were treated with staged surgical excision with 100% immunohistopathological control of lateral margins. Digital pictures were used to facilitate orientation during the several stages of surgery. After a mean follow-up of 60 months, four patients had a recurrence, after 37, 58, 74 and 77 months of follow-up. CONCLUSIONS: Staged surgical excision is superior in clearance and recurrence rates to wide local excision for lentigo maligna and should be considered as the treatment of first choice in national and international guidelines.

Supersymmetric dark matter after LHC run 1.

Different mechanisms operate in various regions of the MSSM parameter space to bring the relic density of the lightest neutralino, [Formula: see text], assumed here to be the lightest SUSY particle (LSP) and thus the dark matter (DM) particle, into the range allowed by astrophysics and cosmology. These mechanisms include coannihilation with some nearly degenerate next-to-lightest supersymmetric particle such as the lighter stau [Formula: see text], stop [Formula: see text] or chargino [Formula: see text], resonant annihilation via direct-channel heavy Higgs bosons H / A, the light Higgs boson h or the Z boson, and enhanced annihilation via a larger Higgsino component of the LSP in the focus-point region. These mechanisms typically select lower-dimensional subspaces in MSSM scenarios such as the CMSSM, NUHM1, NUHM2, and pMSSM10. We analyze how future LHC and direct DM searches can complement each other in the exploration of the different DM mechanisms within these scenarios. We find that the [Formula: see text] coannihilation regions of the CMSSM, NUHM1, NUHM2 can largely be explored at the LHC via searches for [Formula: see text] events and long-lived charged particles, whereas their H / A funnel, focus-point and [Formula: see text] coannihilation regions can largely be explored by the LZ and Darwin DM direct detection experiments. We find that the dominant DM mechanism in our pMSSM10 analysis is [Formula: see text] coannihilation: parts of its parameter space can be explored by the LHC, and a larger portion by future direct DM searches.

The pMSSM10 after LHC run 1.

We present a frequentist analysis of the parameter space of the pMSSM10, in which the following ten soft SUSY-breaking parameters are specified independently at the mean scalar top mass scale [Formula: see text]: the gaugino masses [Formula: see text], the first-and second-generation squark masses [Formula: see text], the third-generation squark mass [Formula: see text], a common slepton mass [Formula: see text] and a common trilinear mixing parameter A, as well as the Higgs mixing parameter [Formula: see text], the pseudoscalar Higgs mass [Formula: see text] and [Formula: see text], the ratio of the two Higgs vacuum expectation values. We use the MultiNest sampling algorithm with [Formula: see text]1.2 [Formula: see text] points to sample the pMSSM10 parameter space. A dedicated study shows that the sensitivities to strongly interacting sparticle masses of ATLAS and CMS searches for jets, leptons [Formula: see text][Formula: see text] signals depend only weakly on many of the other pMSSM10 parameters. With the aid of the Atom and Scorpion codes, we also implement the LHC searches for electroweakly interacting sparticles and light stops, so as to confront the pMSSM10 parameter space with all relevant SUSY searches. In addition, our analysis includes Higgs mass and rate measurements using the HiggsSignals code, SUSY Higgs exclusion bounds, the measurements of [Formula: see text] by LHCb and CMS, other B-physics observables, electroweak precision observables, the cold dark matter density and the XENON100 and LUX searches for spin-independent dark matter scattering, assuming that the cold dark matter is mainly provided by the lightest neutralino [Formula: see text]. We show that the pMSSM10 is able to provide a supersymmetric interpretation of [Formula: see text], unlike the CMSSM, NUHM1 and NUHM2. As a result, we find (omitting Higgs rates) that the minimum [Formula: see text] with 18 degrees of freedom (d.o.f.) in the pMSSM10, corresponding to a [Formula: see text] probability of 30.8 %, to be compared with [Formula: see text] in the CMSSM (NUHM1) (NUHM2). We display the one-dimensional likelihood functions for sparticle masses, and we show that they may be significantly lighter in the pMSSM10 than in the other models, e.g., the gluino may be as light as [Formula: see text]1250 [Formula: see text] at the 68 % CL, and squarks, stops, electroweak gauginos and sleptons may be much lighter than in the CMSSM, NUHM1 and NUHM2. We discuss the discovery potential of future LHC runs, [Formula: see text] colliders and direct detection experiments.

Collider Interplay for Supersymmetry, Higgs and Dark Matter.

We discuss the potential impacts on the CMSSM of future LHC runs and possible [Formula: see text] and higher-energy proton-proton colliders, considering searches for supersymmetry via  [Formula: see text] events, precision electroweak physics, Higgs measurements and dark matter searches. We validate and present estimates of the physics reach for exclusion or discovery of supersymmetry via [Formula: see text] searches at the LHC, which should cover the low-mass regions of the CMSSM parameter space favoured in a recent global analysis. As we illustrate with a low-mass benchmark point, a discovery would make possible accurate LHC measurements of sparticle masses using the MT2 variable, which could be combined with cross-section and other measurements to constrain the gluino, squark and stop masses and hence the soft supersymmetry-breaking parameters [Formula: see text] and [Formula: see text] of the CMSSM. Slepton measurements at CLIC would enable [Formula: see text] and [Formula: see text] to be determined with high precision. If supersymmetry is indeed discovered in the low-mass region, precision electroweak and Higgs measurements with a future circular [Formula: see text] collider (FCC-ee, also known as TLEP) combined with LHC measurements would provide tests of the CMSSM at the loop level. If supersymmetry is not discovered at the LHC, it is likely to lie somewhere along a focus-point, stop-coannihilation strip or direct-channel A / H resonance funnel. We discuss the prospects for discovering supersymmetry along these strips at a future circular proton-proton collider such as FCC-hh. Illustrative benchmark points on these strips indicate that also in this case FCC-ee could provide tests of the CMSSM at the loop level.

The NUHM2 after LHC Run 1.

We make a frequentist analysis of the parameter space of the NUHM2, in which the soft supersymmetry (SUSY)-breaking contributions to the masses of the two Higgs multiplets, [Formula: see text], vary independently from the universal soft SUSY-breaking contributions [Formula: see text] to the masses of squarks and sleptons. Our analysis uses the MultiNest sampling algorithm with over [Formula: see text] points to sample the NUHM2 parameter space. It includes the ATLAS and CMS Higgs mass measurements as well as the ATLAS search for supersymmetric jets + [Formula: see text] signals using the full LHC Run 1 data, the measurements of [Formula: see text] by LHCb and CMS together with other B-physics observables, electroweak precision observables and the XENON100 and LUX searches for spin-independent dark-matter scattering. We find that the preferred regions of the NUHM2 parameter space have negative SUSY-breaking scalar masses squared at the GUT scale for squarks and sleptons, [Formula: see text], as well as [Formula: see text]. The tension present in the CMSSM and NUHM1 between the supersymmetric interpretation of [Formula: see text] and the absence to date of SUSY at the LHC is not significantly alleviated in the NUHM2. We find that the minimum [Formula: see text] with 21 degrees of freedom (dof) in the NUHM2, to be compared with [Formula: see text] in the CMSSM, and [Formula: see text] in the NUHM1. We find that the one-dimensional likelihood functions for sparticle masses and other observables are similar to those found previously in the CMSSM and NUHM1.

Implications of improved Higgs mass calculations for supersymmetric models.

We discuss the allowed parameter spaces of supersymmetric scenarios in light of improved Higgs mass predictions provided by FeynHiggs 2.10.0. The Higgs mass predictions combine Feynman-diagrammatic results with a resummation of leading and subleading logarithmic corrections from the stop/top sector, which yield a significant improvement in the region of large stop masses. Scans in the pMSSM parameter space show that, for given values of the soft supersymmetry-breaking parameters, the new logarithmic contributions beyond the two-loop order implemented in FeynHiggs tend to give larger values of the light CP-even Higgs mass, [Formula: see text], in the region of large stop masses than previous predictions that were based on a fixed-order Feynman-diagrammatic result, though the differences are generally consistent with the previous estimates of theoretical uncertainties. We re-analyse the parameter spaces of the CMSSM, NUHM1 and NUHM2, taking into account also the constraints from CMS and LHCb measurements of [Formula: see text]and ATLAS searches for [Formula: see text] events using 20/fb of LHC data at 8 TeV. Within the CMSSM, the Higgs mass constraint disfavours [Formula: see text], though not in the NUHM1 or NUHM2.

The CMSSM and NUHM1 after LHC Run 1.

We analyze the impact of data from the full Run 1 of the LHC at 7 and 8 TeV on the CMSSM with [Formula: see text] and [Formula: see text] and the NUHM1 with [Formula: see text], incorporating the constraints imposed by other experiments such as precision electroweak measurements, flavour measurements, the cosmological density of cold dark matter and the direct search for the scattering of dark matter particles in the LUX experiment. We use the following results from the LHC experiments: ATLAS searches for events with [Formula: see text] accompanied by jets with the full 7 and 8 TeV data, the ATLAS and CMS measurements of the mass of the Higgs boson, the CMS searches for heavy neutral Higgs bosons and a combination of the LHCb and CMS measurements of [Formula: see text] and [Formula: see text]. Our results are based on samplings of the parameter spaces of the CMSSM for both [Formula: see text] and [Formula: see text] and of the NUHM1 for [Formula: see text] with 6.8[Formula: see text], 6.2[Formula: see text] and 1.6[Formula: see text] points, respectively, obtained using the MultiNest tool. The impact of the Higgs-mass constraint is assessed using FeynHiggs 2.10.0, which provides an improved prediction for the masses of the MSSM Higgs bosons in the region of heavy squark masses. It yields in general larger values of [Formula: see text] than previous versions of FeynHiggs, reducing the pressure on the CMSSM and NUHM1. We find that the global [Formula: see text] functions for the supersymmetric models vary slowly over most of the parameter spaces allowed by the Higgs-mass and the [Formula: see text] searches, with best-fit values that are comparable to the [Formula: see text] for the best Standard Model fit. We provide 95 % CL lower limits on the masses of various sparticles and assess the prospects for observing them during Run 2 of the LHC.

[Can the clinical items of the risk assessment instrument HKT-30 predict to what extent forensic patients will break agreements during the resocialisation phase of treatment?]. / De HKT-30 als instrument voor beslismomenten binnen een tbs-behandeling.

BACKGROUND: Up till now, little research has been done into the factors that psychologists use during a patient's Involuntary Commitment process in order to decide whether the patient should be transferred from the transitional phase of treatment to the pre-release resocialisation phase. In forensic treatment a premature decision can result in a problematical resocialisation phase and prolong the period of treatment. AIM: To find out whether the K-items of the HKT-30, measured in the 12 months prior to the decision-making moment, can predict whether a patient, upon transfer to the resocialisation phase, will likely break agreements made in the transitional phase. METHOD: With logistic regression and roc-analyses, the K-items of the HKT-30 for 94 patients, measured between 2003 and 2009, were used to predict the course and length of these patients' treatment in the resocialisation phase. RESULTS: Some clinical items of the HKT-30 appear to provide a predictive value for the course of the pre-release resocialisation phase. Impulsiveness is one of the risk factors affecting the resocialisation phase. CONCLUSION: Some K-items of the HKT-30 do appear to support the decisions to allow patients receiving forensic inpatient treatment to be transferred to the resocialisation phase.

Coherent Cherenkov radiation from cosmic-ray-induced air showers.

Very energetic cosmic rays entering the atmosphere of Earth will create a plasma cloud moving with almost the speed of light. The magnetic field of Earth induces an electric current in this cloud which is responsible for the emission of coherent electromagnetic radiation. We propose to search for a new effect: Because of the index of refraction of air, this radiation is collimated in a Cherenkov cone. To express the difference from usual Cherenkov radiation, i.e., the emission from a fast-moving electric charge, we call this magnetically induced Cherenkov radiation. We indicate its signature and possible experimental verification.

An exploration of the lived experiences of individuals with relapsed multiple myeloma.

The experience of living with relapsed Multiple Myeloma (myeloma) for eight patients accessing treatment within a haematology unit in a large London hospital is explored in this study. Myeloma is recognised as incurable and is sometimes described as an 'incurable chronic disease' with a main treatment option of chemotherapy. Hermeneutic phenomenology was the methodology used in conducting the study and data were collected through open-ended, unstructured interviews. Findings suggest that living with relapsed myeloma in the context of a chronic illness causes an ever-shifting perspective between illness and wellness consequently maintaining a state of uncertainty. The patients in this study placed importance on the emotional aspect of their experience. Hope, intuitive knowing and a fighting spirit were expressed as required positive elements that enabled living with relapsed myeloma. These assisted in maintaining normality, coping with bad news and adjusting to the illness. Pervading through the themes was the need to control uncertainty. Having strong support from significant others provided something to live for and the necessary social support required to promote a new orientation to life.

The paradoxical image of chemotherapy: a phenomenological description of nurses' experiences of administering chemotherapy.

The paradoxical image of chemotherapy: a phenomenological description of nurses' experiences of administering chemotherapyA sample of nine nurses who were employed within a haematology ward, a bone marrow transplant unit and a chemotherapy outpatient department of a single hospital Trust in the UK, and who regularly administered cytotoxic chemotherapy were recruited to participate in the study. A qualitative phenomenological design was used with a semi-structured interview format. The findings revealed a 'Paradoxical image of chemotherapy' that was related to the overall damaging effects of chemotherapy where it both serves as a curative treatment and 'another chance of life' and also causes damage (morbidity) while it cures. The nurses administering chemotherapy were found to also experience 'damage' as a result of seeing the suffering of their patients and being involved in dilemmas regarding administering chemotherapy treatments. The patient experiences are described from the nurses' perspective.

In situ radiometric mapping as a proxy of sediment contamination: assessment of the underlying geochemical and -physical principles.

Correlations between sediment contaminants like heavy metals or organic micro-compounds and natural or anthropogenic radionuclides ((40)K, (238)U, (232)Th, (137)Cs) facilitates in situ mapping of the contaminated sediment using gamma-ray detectors. These maps can be made quickly and economically using surveys with towed underwater gamma-ray detectors and based on the fundamental correlation of contaminants with radioactivity. This paper aims at an assessment of the geochemical and -physical principles underlying these correlations. This assessment uses multivariate analysis of a data base containing information on radionuclides and contaminants for a large number of sediment samples used to derive radionuclide-contaminant correlations in radiometric mapping projects in freshwater bodies of the Netherlands. More specifically, the aims of this study are to test if these correlations are valid for the entire Dutch freshwater environment and to investigate the validity of the thesis that these correlations are mainly due to the presence of clay.

Effects of high-fat diets with different carbohydrate-to-protein ratios on energy homeostasis in rats with impaired brain melanocortin receptor activity.

Changes in dietary macronutrient composition and/or central nervous system neuronal activity can underlie obesity and disturbed fuel homeostasis. We examined whether switching rats from a diet with high carbohydrate content (HC; i.e., regular chow) to diets with either high fat (HF) or high fat/high protein content at the expense of carbohydrates (LC-HF-HP) causes differential effects on body weight and glucose homeostasis that depend on the integrity of brain melanocortin (MC) signaling. In vehicle-treated rats, switching from HC to either HF or LC-HF-HP feeding caused similar reductions in food intake without alterations in body weight. A reduced caloric intake (-16% in HF and LC-HF-HP groups) required to maintain or increase body weight underlay these effects. Chronic third cerebroventricular infusion of the MC receptor antagonist SHU9119 (0.5 nmol/day) produced obesity and hyperphagia with an increased food efficiency again observed during HF (+19%) and LC-HF-HP (+33%) feeding. In this case, however, HF feeding exaggerated SHU9119-induced hyperphagia and weight gain relative to HC and LC-HF-HP feeding. Relative to vehicle-treated controls, SHU9119 treatment increased plasma insulin (2.8-4 fold), leptin (7.7-15 fold), and adiponectin levels (2.4-3.7 fold), but diet effects were only observed on plasma adiponectin (HC and LC-HF-HP

Caspase-independent exposure of aminophospholipids and tyrosine phosphorylation in bicarbonate responsive human sperm cells.

Only capacitated sperm cells are able to fertilize egg cells, and this process is triggered by high levels of bicarbonate. Bicarbonate renders the plasma membrane more fluid, which is caused by protein kinase A (PKA)-mediated alterations in the phospholipid (PL) bilayer. We studied exposure of phosphatidylserine (PS) and phosphatidylethanolamine (PE) in human sperm cells. Surface exposure of PS and PE on sperm cell activation in vitro was found to be bicarbonate dependent and restricted to the apical area of the head plasma membrane. The PL scrambling in bicarbonate-triggered human sperm was not related to apoptosis, because the incubated cells did not show any signs of caspases or degeneration of mitochondria or DNA. The PL scramblase (PLSCR) gene family has been implicated in this nonspecific, bidirectional PL movement. A 25-kDa isoform of PLSCR was identified that was homogeneously distributed in human sperm cells. We propose that compartment-dependent activation of PKA is required for the surface exposure of aminophospholipids at the apical plasma membrane of sperm cells. Bicarbonate-induced PL scrambling appears to be an important event in the capacitation process, because the entire intact scrambling sperm subpopulation showed extensive tyrosine phosphorylation, which was absent in the nonscrambling subpopulation. The proportion of live cells with PL scrambling corresponded with that showing capacitation-specific chlortetracyclin staining.