The HST Survey of BL Lac Objects: Gravitational Lens Candidates and Other Unusual Sources

We present HST observations of seven unusual objects from the HST ``snapshot survey'' of BL Lac objects, of which four are gravitational lens candidates. In three cases a double point sources is observed: 0033+595, with 1.58 arcsec separation, and 0502+675 and 1440+122, each with $\sim 0.3$ arcsec separation. The last two also show one or more galaxies, which could be either host or lensing galaxies. If any are confirmed as lenses, these BL Lac objects are excellent candidates for measuring H$_0$ via gravitational time delay because of their characteristic rapid, high amplitude variability. An additional advantage is that, like other blazars, they are likely superluminal radio sources, in which case the source plane is mapped out over a period of years, providing strong additional constraints on the lensing mass distribution. The fourth gravitational lens candidate is 1517+656, which is surrounded by three arclets forming an almost perfect ring of radius 2.4 arcsec. If this is indeed an Einstein ring, it is most likely a background source gravitationally lensed by the BL Lac object host galaxy and possibly a surrounding group or cluster. In the extreme case that all four candidates are true lenses, the derived frequency of gravitational lensing in this BL Lac sample would be an order of magnitude higher than in comparable quasar samples. We also report on three other remarkable BL Lac objects: 0138-097, which is surrounded by a large number of close companion galaxies; 0806+524, whose host galaxy contains an uncommon arc-like structure; and 1959+650, which is hosted by a gas rich elliptical galaxy with a prominent dust lane of $\sim 5\times 10^5 M_\odot$.Comment: 29 pages in total, 12 figure

ASCA and contemporaneous ground-based observations of the BL Lacertae objects 1749+096 and 2200+420 (BL Lac)

We present ASCA observations of the radio-selected BL Lacertae objects 1749+096 (z=0.32) and 2200+420 (BL Lac, z=0.069) performed in 1995 Sept and Nov, respectively. The ASCA spectra of both sources can be described as a first approximation by a power law with photon index Gamma ~ 2. This is flatter than for most X-ray-selected BL Lacs observed with ASCA, in agreement with the predictions of current blazar unification models. While 1749+096 exhibits tentative evidence for spectral flattening at low energies, a concave continuum is detected for 2200+420: the steep low-energy component is consistent the high-energy tail of the synchrotron emission responsible for the longer wavelengths, while the harder tail at higher energies is the onset of the Compton component. The spectral energy distributions from radio to gamma-rays are consistent with synchrotron-self Compton emission from a single homogeneous region shortward of the IR/optical wavelengths, with a second component in the radio domain related to a more extended emission region. For 2200+420, comparing the 1995 Nov state with the optical/GeV flare of 1997 July, we find that models requiring inverse Compton scattering of external photons provide a viable mechanism for the production of the highest (GeV) energies during the flare. An increase of the external radiation density and of the power injected in the jet can reproduce the flat gamma-ray continuum observed in 1997 July. A directly testable prediction of this model is that the line luminosity in 2200+420 should vary shortly after (~1 month) a non-thermal synchrotron flare.Comment: 28 pages,6 figures, 5 tables; LaTeX document. accepted for publication in the Astrophysical Journa

HST Observations of the Host Galaxies of BL Lacertae Objects

Six BL Lac objects from the complete 1 Jy radio-selected sample of 34 objects were observed in Cycle 5 with the HST WFPC2 camera to an equivalent limiting flux of mu_I~26 mag/arcsec^2. Here we report results for the second half of this sample, as well as new results for the first three objects, discussed previously by Falomo et al. (1997). In addition, we have analyzed in the same way HST images of three X-ray-selected BL Lacs observed by Jannuzi et al. (1997). The ensemble of 9 BL Lac objects spans the redshift range from z=0.19 to ~1. Host galaxies are clearly detected in seven cases, while the other two, at z~0.258 (redshift highly uncertain) and z=0.997, are not resolved. The HST images constitute a homogeneous data set with unprecedented morphological information between a few tenths of an arcsecond and several arcseconds from the nucleus, allowing us in 6 of the 7 detected host galaxies to rule out definitively a pure disk light profile. The host galaxies are luminous ellipticals with an average absolute magnitude of M_I~-24.6 mag (with dispersion 0.7 mag), more than a magnitude brighter than L* and comparable to brightest cluster galaxies. The morphologies are generally smooth and have small ellipticities (epsilon<0.2). Given such roundness, there is no obvious alignment with the more linear radio structures. In the six cases for which we have HST WFPC2 images in two filters, the derived color profiles show no strong spatial gradients and are as expected for K-corrected passively evolving elliptical galaxies. The host galaxies of the radio-selected and X-ray-selected BL Lacs for this very limited sample are comparable in both morphology and luminosity.Comment: 23 pages, including 6 postscript figures and 3 tables (embedded). Latex requires aaspp4.sty and psfig.sty (not included). Accepted for publication in the Astrophysical Journa

Tuning cell behavior with nanoparticle shape

We investigated how the shape of polymeric vesicles, made by the exact same material, impacts the replication activity and metabolic state of both cancer and non-cancer cell types. First, we isolated discrete geometrical structures (spheres and tubes) from a heterogeneous sample using density-gradient centrifugation. Then, we characterized the cellular internalization and the kinetics of uptake of both types of polymersomes in different cell types (either cancer or non-cancer cells). We also investigated the cellular metabolic response as a function of the shape of the structures internalized and discovered that tubular vesicles induce a significant decrease in the replication activity of cancer cells compared to spherical vesicles. We related this effect to the significant up-regulation of the tumor suppressor genes p21 and p53 with a concomitant activation of caspase 3/7. Finally, we demonstrated that combining the intrinsic shape-dependent effects of tubes with the delivery of doxorubicin significantly increases the cytotoxicity of the system. Our results illustrate how the geometrical conformation of nanoparticles could impact cell behavior and how this could be tuned to create novel drug delivery systems tailored to specific biomedical application

The HST Survey of BL Lacertae Objects. II. Host Galaxies

We have used the HST WFPC2 camera to survey 132 BL Lac objects comprising seven complete radio-, X-ray-, and optically-selected samples. We obtained useful images for 110 targets spanning the redshift range 0 < z < 1.3. In two thirds of the BL Lac images, host galaxies are detected, including nearly all for z < 0.5 (58 of 63). The highest redshift host galaxy detected is in a BL Lac object at z=0.664. In 58 of the 72 resolved host galaxies, a de Vaucouleurs profile is significantly preferred, at >99% confidence, over a pure exponential disk; the two fits are comparable in the remaining 14 cases. These results limit the number of disk systems to at most 8% of BL Lacs (at 99% confidence), and are consistent with all BL~Lac host galaxies being ellipticals. The detected host galaxies are luminous ellipticals with a median absolute K-corrected magnitude of M_R= -23.7 +- 0.6 mag, at least one magnitude brighter than M* and comparable to brightest cluster galaxies. The galaxy morphologies are generally smooth and undisturbed, with small or negligible ellipticities (<0.2). There is no correlation between host galaxy and observed nuclear magnitude or estimated jet power corrected for beaming. If black hole mass is correlated linearly with bulge mass in general, this implies a large range in Eddington ratio. Present data strongly support the unification picture with FR I galaxies constituting the bulk of the parent population of BL Lac objects.Comment: Accepted for publication on ApJ. 38 pages, 8 figure

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance.

IntroductionMucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA.MethodsTwenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers.ResultsA total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance).ConclusionThis manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps

Recommendations for the management of MPS VI: systematic evidence- and consensus-based guidance.

IntroductionMucopolysaccharidosis (MPS) VI or Maroteaux-Lamy syndrome (253200) is an autosomal recessive lysosomal storage disorder caused by deficiency in N-acetylgalactosamine-4-sulfatase (arylsulfatase B). The heterogeneity and progressive nature of MPS VI necessitates a multidisciplinary team approach and there is a need for robust guidance to achieve optimal management. This programme was convened to develop evidence-based, expert-agreed recommendations for the general principles of management, routine monitoring requirements and the use of medical and surgical interventions in patients with MPS VI.Methods26 international healthcare professionals from various disciplines, all with expertise in managing MPS VI, and three patient advocates formed the Steering Committee group (SC) and contributed to the development of this guidance. Members from six Patient Advocacy Groups (PAGs) acted as advisors and attended interviews to ensure representation of the patient perspective. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with expertise and experience managing patients with MPS VI and the manuscript has been evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers.ResultsA total of 93 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions. Consensus was reached on all statements after two rounds of voting. The greatest challenges faced by patients as relayed by consultation with PAGs were deficits in endurance, dexterity, hearing, vision and respiratory function. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance).ConclusionThis manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS VI and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps

Ten years of the Hunter Outcome Survey (HOS) : insights, achievements, and lessons learned from a global patient registry

Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a rare lysosomal storage disease with progressive multisystem manifestations caused by deficient activity of the enzyme iduronate-2-sulfatase. Diseasespecific treatment is available in the form of enzyme replacement therapy with intravenous idursulfase (Elaprase®, Shire). Since 2005, the Hunter Outcome Survey (HOS) has collected real-world, long-term data on the safety and effectiveness of this therapy, as well as the natural history of MPS II. Individuals with a confirmed diagnosis of MPS II who are untreated or who are receiving/have received treatment with idursulfase or bone marrow transplant can be enrolled in HOS. A broad range of disease- and treatment-related information is captured in the registry and, over the past decade, data from more than 1000 patients from 124 clinics in 29 countries have been collected. Evidence generated from HOS has helped to improve our understanding of disease progression in both treated and untreated patients and has extended findings from the formal clinical trials of idursulfase. As a long-term, global, observational registry, various challenges relating to data collection, entry, and analysis have been encountered. These have resulted in changes to the HOS database platform, and novel approaches to maximize the value of the information collected will also be needed in the future. The continued evolution of the registry should help to ensure that HOS provides further insights into the burden of the disease and patient care and management in the coming years