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Studies of young clusters have shown that a large fraction of O-/early B-type stars are in binary systems, where the binary fraction increases with mass. These massive stars are present in clusters of a few Myr, but gradually disappear for older clusters. The lack of detailed studies of intermediate-age clusters has meant that almost no information is available on the multiplicity properties of stars with |$M\lt 4\, {\rm M}_{\odot }$|⁠. In this study we present the first characterization of the binary content of NGC 1850, a 100 Myr-old massive star cluster in the Large Magellanic Cloud, relying on a VLT/MUSE multi-epoch spectroscopic campaign. By sampling stars down to M = 2.5 M⊙, we derive a close binary fraction of 24 ± 5 per cent in NGC 1850, in good agreement with the multiplicity frequency predicted for stars of this mass range. We also find a trend with stellar mass (magnitude), with higher mass (brighter) stars having higher binary fractions. We modelled the radial velocity curves of individual binaries using the joker and constrained the orbital properties of 27 systems, ∼17 per cent of all binaries with reliable radial velocities in NGC 1850. This study has brought to light a number of interesting objects, such as four binaries showing mass functions f (M) > 1.25 M⊙. One of these, star #47, has a peculiar spectrum, explainable with the presence of two discs in the system, around the visible star and the dark companion, which is a black hole candidate. These results confirm the importance and urgency of studying the binary content of clusters of any age. [ABSTRACT FROM AUTHOR]

A black hole candidate orbiting a luminous star in the Large Magellanic Cloud young cluster NGC 1850 (∼100 Myr) has recently been reported based on radial velocity and light-curve modelling. Subsequently, an alternative explanation has been suggested for the system: a bloated post-mass transfer secondary star (M initial ∼ 4–5 M⊙ and M current ∼ 1–2 M⊙) with a more massive, yet luminous companion (the primary). Upon reanalysis of the MUSE spectra, we found that the radial velocity variations originally reported were underestimated (K 2, revised = 176 ± 3 km s−1 versus K 2, original = 140 ± 3 km s−1) because of the weighting scheme adopted in the full-spectrum fitting analysis. The increased radial velocity semi-amplitude translates into a system mass function larger than previously deduced (f revised = 2.83 M⊙versus f original = 1.42 M⊙). By exploiting the spectral disentangling technique, we place an upper limit of 10 per cent of a luminous primary source to the observed optical light in NGC1850 BH1, assuming that the primary and secondary are the only components contributing to the system. Furthermore, by analysing archival near-infrared data, we find clues to the presence of an accretion disc in the system. These constraints support a low-mass post-mass transfer star but do not provide a definitive answer whether the unseen component in NGC1850 BH1 is indeed a black hole. These results predict a scenario where, if a primary luminous source of mass M  ≥ 4.7 M⊙ is present in the system (given the inclination and secondary mass constraints), it must be hidden in a optically thick disc to be undetected in the MUSE spectra. [ABSTRACT FROM AUTHOR]

Young star clusters enable us to study the effects of stellar rotation on an ensemble of stars of the same age and across a wide range in stellar mass and are therefore ideal targets for understanding the consequences of rotation on stellar evolution. We combine MUSE spectroscopy with HST photometry to measure the projected rotational velocities (V sin  i) of 2184 stars along the split main sequence and on the main sequence turn-off (MSTO) of the 100 Myr-old massive (⁠|$10^5\, {\rm M_{\odot }}$|⁠) star cluster NGC 1850 in the Large Magellanic Cloud. At fixed magnitude, we observe a clear correlation between V sin  i and colour, in the sense that fast rotators appear redder. The average V sin  i values for stars on the blue and red branches of the split main sequence are |$\sim \! 100\, {\rm km\, s^{-1}}$| and |$\sim \! 200\, {\rm km\, s^{-1}}$|⁠ , respectively. The values correspond to about |$25-30{{\ \rm per\ cent}}$| and |$50-60{{\ \rm per\ cent}}$| of the critical rotation velocity and imply that rotation rates comparable to those observed in field stars of similar masses can explain the split main sequence. Our spectroscopic sample contains a rich population of ∼200 fast rotating Be stars. The presence of shell features suggests that 23 per cent of them are observed through their decretion discs, corresponding to a disc opening angle of 15 degrees. These shell stars can significantly alter the shape of the MSTO, hence care should be taken when interpreting this photometric feature. Overall, our findings impact our understanding of the evolution of young massive clusters and provide new observational constraints for testing stellar evolutionary models. [ABSTRACT FROM AUTHOR]

We report on the detection of a black hole (NGC 1850 BH1) in the ∼100-Myr-old massive cluster NGC 1850 in the Large Magellanic Cloud. It is in a binary system with a main-sequence turn-off star (4.9 ± 0.4 M⊙), which is starting to fill its Roche lobe and is becoming distorted. Using 17 epochs of Very Large Telescope/Multi-Unit Spectroscopic Explorer observations, we detected radial velocity variations exceeding 300 km s−1 associated with the target star, linked to the ellipsoidal variations measured by the fourth phase of the Optical Gravitational Lensing Experiment in the optical bands. Under the assumption of a semidetached system, the simultaneous modelling of radial velocity and light curves constrains the orbital inclination of the binary to 38° ± 2°, resulting in a true mass of the unseen companion of |$11.1_{-2.4}^{+2.1}\,{\rm M}_{\odot }$|⁠. This represents the first direct dynamical detection of a black hole in a young massive cluster, opening up the possibility of studying the initial mass function and the early dynamical evolution of such compact objects in high-density environments. [ABSTRACT FROM AUTHOR]

Nearly all of the well-studied ancient globular clusters (GCs), in the Milky Way and in nearby galaxies, show star-to-star variations in specific elements (e.g. He, C, N, O, Na, and Al), known as 'multiple populations' (MPs). However, MPs are not restricted to ancient clusters, with massive clusters down to ∼2 Gyr showing signs of chemical variations. This suggests that young and old clusters share the same formation mechanism but most of the work to date on younger clusters has focused on N variations. Initial studies even suggested that younger clusters may not host spreads in other elements beyond N (e.g. Na), calling into question whether these abundance variations share the same origin as in the older GCs. In this work, we combine Hubble Space Telescope (HST) photometry with Very Large Telescope (VLT)/Multi-Unit Spectroscopic Explorer (MUSE) spectroscopy of a large sample of red giant branch (RGB) stars (338) in the Large Magellanic Cloud cluster NGC 1978, the youngest globular to date with reported MPs in the form of N spreads. By combining the spectra of individual RGB stars into N-normal and N-enhanced samples, based on the 'chromosome map' derived from HST , we search for mean abundance variations. Based on the NaD line, we find a Na difference of Δ[Na/Fe] = 0.07 ± 0.01 between the populations. While this difference is smaller than typically found in ancient GCs (which may suggest a correlation with age), this result further confirms that the MP phenomenon is the same, regardless of cluster age and host galaxy. As such, these young clusters offer some of the strictest tests for theories on the origin of MPs. [ABSTRACT FROM AUTHOR]

The spectroscopic and photometric signals of the star-to-star abundance variations found in globular clusters seem to be correlated with global parameters like the cluster's metallicity, mass, and age. Understanding this behaviour could bring us closer to the origin of these intriguing abundance spreads. In this work we use deep HST photometry to look for evidence of abundance variations in the main sequence of a young massive cluster NGC 419 (∼105 M⊙, ∼1.4 Gyr). Unlike previous studies, here we focus on stars in the same mass range found in old globulars (∼0.75–1 M⊙), where light elements variations are detected. We find no evidence for N abundance variations among these stars in the Un − B and U − B colour–magnitude diagrams of NGC 419. This is at odds with the N variations found in old globulars like 47 Tuc, NGC 6352, and NGC 6637 with similar metallicity to NGC 419. Although the signature of the abundance variations characteristic of old globulars appears to be significantly smaller or absent in this young cluster, we cannot conclude if this effect is mainly driven by its age or its mass. [ABSTRACT FROM AUTHOR]

Observed mass-to-light ratios (M / L) of metal-rich globular clusters (GCs) disagree with theoretical predictions. This discrepancy is of fundamental importance since stellar population models provide the stellar masses that underpin most of extragalactic astronomy, near and far. We have derived radial velocities for 1622 stars located in the centres of 59 Milky Way GCs – 12 of which have no previous kinematic information – using integral-field unit data from the WAGGS project. Using N -body models, we determine dynamical masses and M / L V for the studied clusters. Our sample includes NGC 6528 and NGC 6553, which extend the metallicity range of GCs with measured M / L up to [Fe/H] ∼ −0.1 dex. We find that metal-rich clusters have M / L V more than two times lower than what is predicted by simple stellar population models. This confirms that the discrepant M / L –[Fe/H] relation remains a serious concern. We explore how our findings relate to previous observations, and the potential causes for the divergence, which we conclude is most likely due to dynamical effects. [ABSTRACT FROM AUTHOR]

We investigate the morphology of the colour–magnitude diagram (CMD) of the open cluster NGC 2509 in comparison with other Galactic open clusters of similar age using Gaia photometry. At |${\sim}900\,\rm {Myr}$| Galactic open clusters in our sample all show an extended main sequence turnoff (eMSTO) with the exception of NGC 2509, which presents an exceptionally narrow CMD. Our analysis of the Gaia data rules out differential extinction, stellar density, and binaries as a cause for the singular MSTO morphology in this cluster. We interpret this feature as a consequence of the stellar rotation distribution within the cluster and present the analysis with mesa Isochrones and Stellar Tracks (MIST) stellar evolution models that include the effect of stellar rotation on which we based our conclusion. In particular, these models point to an unusually narrow range of stellar rotation rates (Ω/Ωcrit, ZAMS = [0.4, 0.6]) within the cluster as the cause of this singular feature in the CMD of NGC 2509. Interestingly, models that do not include rotation are not as good at reproducing the morphology of the observed CMD in this cluster. [ABSTRACT FROM AUTHOR]

We compare the results of a large grid of N -body simulations with the surface brightness and velocity dispersion profiles of the globular clusters ω Cen and NGC 6624. Our models include clusters with varying stellar-mass black hole retention fractions and varying masses of a central intermediate-mass black hole (IMBH). We find that an |$\sim 45\, 000$| M⊙ IMBH, whose presence has been suggested based on the measured velocity dispersion profile of ω Cen, predicts the existence of about 20 fast-moving, m > 0.5 M⊙, main-sequence stars with a (1D) velocity v > 60 km s−1 in the central 20 arcsec of ω Cen. However, no such star is present in the HST /ACS proper motion catalogue of Bellini et al. (2017), strongly ruling out the presence of a massive IMBH in the core of ω Cen. Instead, we find that all available data can be fitted by a model that contains 4.6 per cent of the mass of ω Cen in a centrally concentrated cluster of stellar-mass black holes. We show that this mass fraction in stellar-mass BHs is compatible with the predictions of stellar evolution models of massive stars. We also compare our grid of N -body simulations with NGC 6624, a cluster recently claimed to harbour a 20 000 M⊙ black hole based on timing observations of millisecond pulsars. However, we find that models with M IMBH > 1000 M⊙ IMBHs are incompatible with the observed velocity dispersion and surface brightness profile of NGC 6624, ruling out the presence of a massive IMBH in this cluster. Models without an IMBH provide again an excellent fit to NGC 6624. [ABSTRACT FROM AUTHOR]

In our HST photometric survey, we have been searching for multiple stellar populations (MPs) in Magellanic Clouds (MCs) massive star clusters which span a significant range of ages (∼1.5–11 Gyr). In the previous papers of the series, we have shown that the age of the cluster represents one of the key factors in shaping the origin of the chemical anomalies. Here, we present the analysis of four additional clusters in the MCs, namely Lindsay 38, Lindsay 113, NGC 2121, and NGC 2155, for which we recently obtained new UV HST observations. These clusters are more massive than ∼104 M⊙ and have ages between ∼2.5 and ∼6 Gyr, i.e. located in a previously unexplored region of the cluster age/mass diagram. We found chemical anomalies, in the form of N spreads, in three out of four clusters in the sample, namely in NGC 2121, NGC 2155, and Lindsay 113. By combining data from our survey and HST photometry for three additional clusters in the Milky Way (namely 47 Tuc, M15, and NGC 2419), we show that the extent of the MPs in the form of N spread is a strong function of age, with older clusters having larger N spreads with respect to the younger ones. Hence, we confirm that cluster age plays a significant role in the onset of MPs. [ABSTRACT FROM AUTHOR]

We report the spectroscopic discovery of abundance spreads (i.e. multiple populations) in the ∼2 Gyr old cluster in the LMC, Hodge 6. We use low-resolution VLT FORS2 spectra of 15 member stars in the cluster to measure their CN and CH band strengths at ≃3883 and 4300 Å, respectively, as well as [C/Fe] and [N/Fe] abundances. We find a subpopulation of two stars that are enriched in nitrogen, and we conclude that this subpopulation is evidence of multiple populations in Hodge 6. This is the second ∼2 Gyr old cluster (the first being NGC 1978 in the LMC) to show multiple populations and the first spectroscopic detection of MPs in a cluster of this age. This result is interesting as it hints at a possible relationship between the disappearance of extended main sequence turn-offs in clusters younger than ∼2 Gyr and the onset of multiple populations at ∼2 Gyr, which should be explored further. [ABSTRACT FROM AUTHOR]

We present an analysis of the relatively low mass (∼2400 M⊙), ∼800 Myr, Galactic open cluster, NGC 2818, using Gaia DR2 results combined with VLT/FLAMES spectroscopy. Using Gaia DR2 proper motions and parallax measurements, we are able to select a clean sample of cluster members. This cluster displays a clear extended main sequence turn-off (eMSTO), a phenomenon previously studied mainly in young and intermediate age massive clusters in the Magellanic clouds. The main sequence of NGC 2818 is extremely narrow, with a width of ∼0.01 magnitudes (G BP– G RP), suggesting very low levels of differential extinction. Using VLT/FLAMES spectroscopy of 60 cluster members to measure the rotational velocity of the stars (V sin i), we find that stars on the red side of the eMSTO have high V  sin i (>160 km s−1) while stars on the blue side have low V  sin i (<160 km s−1), in agreement with model predictions. The cluster also follows the previously discovered trend between the age of the cluster and the extent of the eMSTO. We conclude that stellar rotation is the likely cause of the eMSTO phenomenon. [ABSTRACT FROM AUTHOR]

We present adaptive optics (AO)-assisted integral-field spectroscopy of the intermediate-age star cluster NGC 419 in the Small Magellanic Cloud. By investigating the cluster dynamics and the rotation properties of main-sequence turn-off (MSTO) stars, we demonstrate the power of AO-fed MUSE observations for this class of objects. Based on $$1\, 049$$ radial velocity measurements, we determine a dynamical cluster mass of $$1.4\pm 0.2\times 10^5\, {\rm M_\odot}$$ and a dynamical mass-to-light ratio of 0.67 ± 0.08, marginally higher than simple stellar population predictions for a Kroupa initial mass function. A stacking analysis of spectra at both sides of the extended MSTO reveals significant rotational broadening. Our analysis further provides tentative evidence that red MSTO stars rotate faster than their blue counterparts. We find average V sin  i values of $$87\pm 16$$ and $$130\pm 22\, {\rm km\, s^{-1}}$$ for blue and red MSTO stars, respectively. Potential systematic effects due to the low-spectral resolution of MUSE can reach $$30\, {\rm km\, s^{-1}}$$ but the difference in V sin  i between the populations is unlikely to be affected. [ABSTRACT FROM AUTHOR]

We have recently shown that the ~2 Gyr old Large Magellanic Cloud star cluster NGC 1978 hosts multiple populations in terms of star-to-star abundance variations in [N/Fe]. These can be seen as a splitting or spread in the subgiant and red giant branches (SGB and RGB) when certain photometric filter combinations are used. Because of its relative youth, NGC 1978 can be used to place stringent limits on whether multiple bursts of star formation have taken place within the cluster, as predicted by some models for the origin of multiple populations. We carry out two distinct analyses to test whether multiple star formation epochs have occurred within NGC 1978. First, we use ultraviolet colour--magnitude diagrams (CMDs) to select stars from the first and second population along the SGB, and then compare their positions in optical CMDs, where the morphology is dominantly controlled by age as opposed to multiple population effects. We find that the two populations are indistinguishable, with age differences of 1 ± 20 Myr between them. This is in tension with predictions from the asymptotic giant branch scenario for the origin of multiple populations. Second, we estimate the broadness of the main-sequence turn-off (MSTO) of NGC 1978 and we report that it is consistent with the observational errors. We find an upper limit of ~65 Myr on the age spread in the MSTO of NGC 1978. This finding is in conflict with the age spread scenario as origin of the extended MSTO in intermediate-age clusters, while it fully supports predictions from the stellar rotation model. [ABSTRACT FROM AUTHOR]

We present the third paper about our ongoing Hubble Space Telescope survey for the search for multiple stellar populations (MPs) within Magellanic Cloud clusters. We report here the analysis of NGC 419, an ~1.5 Gyr old, massive (≳2 × 105 M⊙) star cluster in the Small Magellanic Cloud (SMC). By comparing our photometric data with stellar isochrones, we set a limit on [N/Fe] enhancement of ≲+0.5 dex and hence we find that no MPs are detected in this cluster. This is surprising because in the first two papers of this series, we found evidence for MPs in four other SMC clusters (NGC 121; Lindsay 1, NGC 339, NGC 416), aged from 6 Gyr up to ~10-11 Gyr. This finding raises the question whether age could play a major role in theMPs phenomenon. Additionally, our results appear to exclude mass or environment as the only key factors regulating the existence of a chemical enrichment, since all clusters studied so far in this survey are equally massive (~1-2 × 105 M⊙) and no particular patterns are found when looking at their spatial distribution in the SMC. [ABSTRACT FROM AUTHOR]

Recent photometric analyses of the colour-magnitude diagrams of young massive clusters (YMCs) have found evidence for splitting in the main sequence and extended main-sequence turn-offs, both of which have been suggested to be caused by stellar rotation. Comparison of the observed main-sequence splitting with models has led various authors to suggest a rather extreme stellar rotation distribution, with a minority (10-30 per cent) of stars with low rotational velocities and the remainder (70-90 per cent) of stars rotating near the critical rotation (i.e. near break-up). We test this hypothesis by searching for Be stars within two YMCs in the Large Magellanic Cloud (NGC 1850 and NGC 1856), which are thought to be critically rotating stars with decretion discs that are (partially) ionized by their host stars. In both clusters, we detect large populations of Be stars at the main-sequence turn-off (~30-60?per?cent of stars), which supports previous suggestions of large populations of rapidly rotating stars within massive clusters. [ABSTRACT FROM AUTHOR]

Background: The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. Methods: Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. Results and discussion: A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84 % of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74 % of prescribers and 84 % of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. Conclusion: The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic medicines. [ABSTRACT FROM AUTHOR]

Objective: Management options for colorectal cancer have expanded in recent years. We estimated average lifetime cost of care for colorectal cancer in Ireland in 2008, from the health care payer perspective. Method: A decision tree model was developed in Microsoft EXCEL. Site and stage-specific treatment pathways were constructed from guidelines and validated by expert clinical opinion. Health care resource use associated with diagnosis, treatment and follow-up were obtained from the National Cancer Registry Ireland ( n=1,498 cancers diagnosed during 2004-2005) and three local hospital databases ( n=155, 142 and 46 cases diagnosed in 2007). Unit costs for hospitalisation, procedures, laboratory tests and radiotherapy were derived from DRG costs, hospital finance departments, clinical opinion and literature review. Chemotherapy costs were estimated from local hospital protocols, pharmacy departments and clinical opinion. Uncertainty was explored using one-way and probabilistic sensitivity analysis. Results: In 2008, the average (stage weighted) lifetime cost of managing a case of colorectal cancer was €39,607. Average costs were 16% higher for rectal (€43,502) than colon cancer (€37,417). Stage I disease was the least costly (€23,688) and stage III most costly (€48,835). Diagnostic work-up and follow-up investigations accounted for 4 and 5% of total costs, respectively. Cost estimates were most sensitive to recurrence rates and prescribing of biological agents. Conclusion: This study demonstrates the value of using existing data from national and local databases in contributing to estimating the cost of managing cancer. The findings illustrate the impact of biological agents on costs of cancer care and the potential of strategies promoting earlier diagnosis to reduce health care resource utilisation and care costs. [ABSTRACT FROM AUTHOR]

Background:Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55-74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55-74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60.Methods:A state-transition model was used to estimate costs and outcomes for each screening scenario vs no screening. A third party payer perspective was adopted. Probabilistic sensitivity analyses were undertaken.Results:All scenarios would be considered highly cost-effective compared with no screening. The lowest incremental cost-effectiveness ratio (ICER vs no screening \[euro]589 per quality-adjusted life-year (QALY) gained) was found for FSIG, followed by FIT (\[euro]1696) and gFOBT (\[euro]4428); gFOBT was dominated. Compared with FSIG, FIT was associated with greater gains in QALYs and reductions in lifetime cancer incidence and mortality, but was more costly, required considerably more colonoscopies and resulted in more complications. Results were robust to variations in parameter estimates.Conclusion:Population-based screening based on FIT is expected to result in greater health gains than a policy of gFOBT (with reflex FIT) or once-only FSIG, but would require significantly more colonoscopy resources and result in more individuals experiencing adverse effects. Weighing these advantages and disadvantages presents a considerable challenge to policy makers. [ABSTRACT FROM AUTHOR]

To describe the pharmacoeconomic assessment process in Ireland and to provide examples of recent appraisals and the subsequent impact on pricing and reimbursement decisions. The pharmacoeconomic appraisals conducted by the National Centre for Pharmacoeconomics (NCPE) between September 2006 and February 2009 were reviewed. The NCPE recommendations and subsequent reimbursement decisions by the Health Service Executive (HSE) were recorded. Recommendations made by the NCPE were compared with those of UK agencies. The duration of the NCPE pharmacoeconomic process and the time from marketing authorization to reimbursement was estimated. The budget impact assessments from the pharmaceutical companies were reviewed and compared for consistency. The NCPE conducted 12 single technology appraisals during the study period. Eight of the medicines assessed were either recommended as a cost-effective use of resources or recommended with certain restrictions, and were funded by the HSE. Of the four medicines that were not considered cost effective, two were reimbursed after a price reduction was negotiated and the remaining two were not. The NCPE recommendations concurred with those of the UK agencies for the majority of appraisals, with the exception of sunitinib and lapatinib. The average duration of the NCPE process was 2.7 months. The average time from marketing authorization to reimbursement was 7 months. The review of budget impact assessments highlighted a high degree of variability between submissions. The findings of this review highlight the efficiency of the pharmacoeconomic process and the acceptance of the NCPE recommendations by the HSE for pricing and reimbursement decisions. NCPE recommendations broadly concurred with those of UK agencies for the majority of appraisals. [ABSTRACT FROM AUTHOR]

This manuscript describes a direct comparison between radiation treatment plans in terms of dosimetric outcomes created by two different IMRT systems: TomoTherapy HiArt™ and dynamic linac intensity-modulated radiotherapy (dIMRT). Three patient cases were selected (with disease in different anatomical areas): vertebral metastasis re-treatment, radical prostate therapy and an ethmoid sarcoma re-treatment. Each case presents significant and varying dosimetric difficulties with respect to avoidance of adjacent organs. The patients were each planned and treated at the Cromwell Hospital (London, UK) using the TomoTherapy HiArt™ system, with planning replicated at St Bartholomew's Hospital (London, UK) using Eclipse Treatment Planning System and a 6EX linac with a 120-leaf multileaf collimator (Varian Medical Systems). For both modalities, all treatment plans conformed to the stringent clinical dose constraints set. For the vertebral body re-treatment, both techniques demonstrated adequate and similar planning target volume (PTV) coverage and sparing of the spinal cord. The critical structure sparing and Ply coverage for the prostate treatment was again similar for both modalities. For re-treatment of the paediatric ethmoid sarcoma, tomotherapy was able to produce slightly better organ sparing whilst producing PTV coverage similar to linac dIMRT. The data presented in this manuscript demonstrate subtle dosimetric differences between the two techniques but no marked advantage with either system. Therefore, other factors may need to be considered when making a decision between tomotherapy and linac dIMRT. [ABSTRACT FROM AUTHOR]

Misuse of prescription sedatives is a significant problem for addiction treatment services. The aim of this study was to examine the prescribing of diazepam in disadvantaged Irish communities, and to identify factors which may predict diazepam consumption in that population. We examined prescribing trends for those aged 16–69 years in 2002 in a region of the state-funded General Medical Services Scheme. Material deprivation was based on the 2002 Small Area Health Research Unit (SAHRU) deprivation index. The average defined daily dose (DDD) was calculated and logistic regression analysis was used to predict diazepam use by age, gender and deprivation index. Results showed that patients living in the most-deprived areas were more likely to receive diazepam than patients living in the least-deprived areas (OR = 1.21, 95% CI 1.15–1.27). Female patients living in the most-deprived areas were also more likely to receive diazepam than those living in the least-deprived areas (OR = 1.36, 95% CI 1.18–1.57). It is concluded that there is a pattern of higher diazepam prescribing in areas of greatest deprivation, where prescription sedatives play a complex role within troubled families. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

To evaluate the effect of publicity surrounding the Women’s Health Initiative (WHI) and Million Women (MW) studies on prescribing of all hormone replacement therapy (HRT) preparations and bisphosphonates in Ireland. The General Medical Services (GMS) prescription database was used to identify the study population. Prescriptions were identified for HRT and bisphosphonate preparations [using WHO Anatomical Therapeutic Chemical (ATC) classification codes] in female patients aged 45–69 years in Ireland during a 4-year study period (January 2001–December 2004). Prescription rates were calculated monthly. Prevalence and incidence of HRT use was examined. There was a significant reduction in prevalence for all HRT preparations following the WHI trial (test for change in trend p<0.0001), which persisted after the MW study. The incidence of combined oestrogen/progestogen HRT declined after the WHI trial (test for change in trend p=0.004). Bisphosphonate prescribing showed a significant increase throughout the study period ( p<0.0001). The findings suggest that coverage surrounding the publication of clinical trials appears to have had a negative impact on the rate of HRT prescribing. The findings regarding the coincident increase in use of bisphosphonates may suggest that prescribers and users were less likely to regard HRT as an appropriate therapy in the management of osteoporosis for some time before guidance was issued by the regulatory authorities. [ABSTRACT FROM AUTHOR]

Radiotherapy of the posterior fossa for medulloblastoma treatment can induce ototoxicity, especially when combined with cisplatin chemotherapy. Sensorineural hearing loss can be severe enough to cause permanent disability, which may compromise cognitive development in paediatric patients. This study evaluates the sparing of the cochlea in conventional radiotherapy, three-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT). CT scans of three patients were used to plan posterior fossa radiotherapy using coplanar beam arrangements. The posterior fossa and the cochlea were contoured as well as other organs-at-risk (non-posterior fossa brain, lenses, optic nerves, pituitary and cervical spinal cord). Three treatment plans were compared: conventional two-dimensional treatment (parallel-opposed lateral pair); 3D-CRT (two wedged posterior oblique fields); and a four-field coplanar IMRT plan. 3D-CRT and IMRT reduced cochlear doses to less than 70% of the mean target dose. These plans also reduced dose to the non-posterior fossa brain and cervical spinal cord. IMRT showed no advantage over 3D-CRT in sparing the optic nerves and lenses, compared with 3D-CRT. Normal tissue doses were higher in both conformal techniques than in the IMRT plans. Conformal techniques reduced the dose to the cochlea, non-posterior fossa brain and cervical spinal cord. The small size and proximity to the planning target volume (PTV) of the cochlea limited the effectiveness of the IMRT plan. Coplanar 3D-CRT was judged superior to coplanar IMRT, particularly in children, because it achieved adequate sparing of the cochlea and anterior cranial structures, such as the lenses and optic nerves, without compromising the dose to the posterior fossa. [ABSTRACT FROM AUTHOR]

The efficacy of abamectin 1%, when injected subcutancously in cattle at a dose of 200 μg/kg body weight, against the larval stages (grubs) of the fly Dermatobia hominis was evaluated in two trials in endemic areas of Brazil and Argentina. Eighteen Holstein x Brahman castrated males and 16 Brahman-cross with natural infestations were used. Larvae were counted by instar in situ on both sides of each animal before treatment, and were expressed, identified as to stage and classified as live or dead 10 days after treatment. Further larval counts were made periodically until day 79 to evaluate the degree of reinfestation and the stage of larval development. Reinfestation was first detected in the abamectin-treated cattle on day 44. Live larvae were found on 6-8 (Argentina) and on all (Brazil) controls at each posttreatment examination. The difference in numbers of live larvae between treatment groups was statistically significant ( P<0.05) at all post-treatment examinations. These data show that abamectin at a dose of 200 μg/kg body weight is highly effective in the treatment and control of established parasitic stages of D. hominis in cattle. No adverse reactions were observed in any of the treated animals. [ABSTRACT FROM AUTHOR]