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| 6. |
- Veres, P., et al.
(author)
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Observation of inverse Compton emission from a long gamma-ray burst
- 2019
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In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 575:7783, s. 459-
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Journal article (peer-reviewed)abstract
- Long-duration gamma-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectron volt-to-mega electronvoltband, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission(1,2). Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands(1-6). The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock(7-9). Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C(10,11). Here we report multifrequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 x 10(-6) to 10(12) electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.
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| 7. |
- Andrews, Jennifer E., et al.
(author)
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SN 2017gmr : An Energetic Type II-P Supernova with Asymmetries
- 2019
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 885:1
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Journal article (peer-reviewed)abstract
- We present high-cadence UV, optical, and near-infrared data on the luminous Type II-P supernova SN;2017gmr from hours after discovery through the first 180 days. SN;2017gmr does not show signs of narrow, high-ionization emission lines in the early optical spectra, yet the optical light-curve evolution suggests that an extra energy source from circumstellar medium (CSM) interaction must be present for at least 2 days after explosion. Modeling of the early light curve indicates a ?500 R progenitor radius, consistent with a rather compact red supergiant, and late-time luminosities indicate that up to 0.130;;0.026 M of Ni-56 are present, if the light curve is solely powered by radioactive decay, although the Ni-56 mass may be lower if CSM interaction contributes to the post-plateau luminosity. Prominent multipeaked emission lines of H? and [O i] emerge after day 154, as a result of either an asymmetric explosion or asymmetries in the CSM. The lack of narrow lines within the first 2 days of explosion in the likely presence of CSM interaction may be an example of close, dense, asymmetric CSM that is quickly enveloped by the spherical supernova ejecta.
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| 8. |
- Burisch, J, et al.
(author)
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Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study
- 2019
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:3, s. 423-433
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Journal article (peer-reviewed)abstract
- The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).DesignPatients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.ResultsIn total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).ConclusionDespite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.
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| 9. |
- LeBlanc, K, et al.
(author)
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Quality of Life after Hernia Surgery
- 2015
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In: Hernia : the journal of hernias and abdominal wall surgery. - 1248-9204. ; 19 Suppl 1, s. S127-31
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Journal article (peer-reviewed)
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| 10. |
- Meyer, Esther, et al.
(author)
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Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
- 2017
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49, s. 223-237
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Journal article (peer-reviewed)abstract
- Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.
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| 11. |
- Christiansen, J. S., et al.
(author)
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Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations
- 2016
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In: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:6
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Journal article (peer-reviewed)abstract
- Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
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| 14. |
- Collett-Solberg, Paulo F., et al.
(author)
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Diagnosis, Genetics, and Therapy of Short Stature in Children : A Growth Hormone Research Society International Perspective
- 2019
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In: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 92:1, s. 1-14
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Journal article (peer-reviewed)abstract
- The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
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| 15. |
- Dastidar, Raya, et al.
(author)
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SN 2015ba : a Type IIP supernova with a long plateau
- 2018
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 479:2, s. 2421-2442
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Journal article (peer-reviewed)abstract
- We present optical photometry and spectroscopy from about a week after explosion to similar to 272 d of an atypical Type IIP supernova, SN 2015ba, which exploded in the edge-on galaxy IC 1029. SN 2015ba is a luminous event with an absolute V-band magnitude of -17.1 +/- 0.2 mag at 50 d since explosion and has a long plateau lasting for similar to 123 d. The distance to the SN is estimated to be 34.8 +/- 0.7 Mpc using the expanding photosphere and standard candle methods. High-velocity H Balmer components constant with time are observed in the late-plateau phase spectra of SN 2015ba, which suggests a possible role of circumstellar interaction at these phases. Both hydrodynamical and analytical modelling suggest a massive progenitor of SN 2015ba with a pre-explosion mass of 24-26 M-circle dot. However, the nebular spectra of SN 2015ba exhibit insignificant levels of oxygen, which is otherwise expected from a massive progenitor. This might be suggestive of the non-monotonical link between O-core masses and the zero-age main sequence mass of pre-supernova stars and/or uncertainties in the mixing scenario in the ejecta of supernovae.
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- Paice, J. A., et al.
(author)
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A black hole X-ray binary at similar to 100 Hz : multiwavelength timing of MAXIJ1820+070 with HiPERCAM and NICER
- 2019
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In: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966 .- 1745-3925 .- 1745-3933. ; 490:1, s. L62-L66
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Journal article (peer-reviewed)abstract
- We report on simultaneous sub-second optical and X-ray timing observations of the low-mass X-ray binary black hole candidate MAXI J1820+070. The bright 2018 outburst rise allowed simultaneous photometry in five optical bands (ugrizs) with HiPERCAM/GTC (Optical) at frame rates over 100 Hz, together with NICER/ISS observations (X-rays). Intense (factor of 2) red flaring activity in the optical is seen over a broad range of time-scales down to similar to 10 ms. Cross-correlating the bands reveals a prominent anticorrelation on time-scales of similar to seconds, and a narrow sub-second correlation at a lag of approximate to+165 ms (optical lagging X-rays). This lag increases with optical wavelength, and is approximately constant over Fourier frequencies of similar to 0.3-10 Hz. These features are consistent with an origin in the inner accretion flow and jet base within similar to 5000 Gravitational radii. An additional similar to+5 s lag feature may be ascribable to disc reprocessing. MAXI J1820+070 is the third black hole transient to display a clear similar to 0.1 s optical lag, which may be common feature in such objects. The sub-second lag variation with wavelength is novel, and may allow constraints on internal shock jet stratification models.
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| 19. |
- Spiegel, D. A., et al.
(author)
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Surgical Care and Health Systems
- 2015
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 39:9, s. 2132-2139
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Journal article (peer-reviewed)abstract
- BACKGROUND: While surgical care impacts a wide variety of diseases and conditions with non-operative and operative services, both preventive and curative, there has been little discussion concerning how surgery might be integrated within the health system of a low and middle-income country (LMIC), nor how strengthening surgical services may improve health systems and population health. METHODS: We reviewed reports from several meetings of the working group on health systems strengthening of the Global Initiative for Emergency and Essential Surgical Care, and also performed a review of the literature including the search terms "surgery," "health system," "developing country," "health systems strengthening," "health information system," "financing," "governance," and "integration." RESULTS: The literature search revealed no reports which focused on the integration of surgical services within a health system or as a component of health system strengthening. A conceptual model of how surgical care might be integrated within a health system is proposed, based on the discussions of our working group, combined with sources from the medical literature, and utilizing the World Health Organization's conceptual model of a health system. CONCLUSIONS: Strengthening the delivery of surgical services in LMICs will require inputs at multiple levels within a health system, and this effort will require the coalescence of committed individuals and organizations, supported by civil society.
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| 20. |
- Conte, Michael S., et al.
(author)
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Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia
- 2019
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In: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 58:1, s. S1-S109
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Journal article (peer-reviewed)abstract
- Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.
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| 23. |
- Das, S, et al.
(author)
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Sunlight Assisted Photocatalytic Degradation of Ciprofloxacin in Water Using Fe Doped ZnO Nanoparticles for Potential Public Health Applications
- 2018
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In: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 15:11
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Journal article (peer-reviewed)abstract
- Antibiotic residues in the aquatic environment have the potential to induce resistance in environmental bacteria, which ultimately might get transferred to pathogens making treatment of diseases difficult and poses a serious threat to public health. If antibiotic residues in the environment could be eliminated or reduced, it could contribute to minimizing antibiotic resistance. Towards this objective, water containing ciprofloxacin was treated by sunlight-assisted photocatalysis using Fe- doped ZnO nanoparticles for assessing the degradation potential of this system. Parameters like pH, temperature, catalytic dosage were assessed for the optimum performance of the system. To evaluate degradation of ciprofloxacin, both spectrophotometric as well as microbiological (loss of antibiotic activity) methods were employed. 100 mg/L Fe-doped ZnO nanoparticle catalyst and sunlight intensity of 120,000–135,000 lux system gave optimum performance at pH 9 at 30 °C and 40 °C. Under these conditions spectrophotometric analysis showed complete degradation of ciprofloxacin (10 mg/L) at 210 min. Microbiological studies showed loss of antibacterial activity of the photocatalytically treated ciprofloxacin-containing water against Staphylococcus aureus (108 CFU) in 60 min and for Escherichia coli (108 CFU) in 75 min. The developed system, thus possess a potential for treatment of antibiotic contaminated waters for eliminating/reducing antibiotic residues from environment.
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| 29. |
- Misra, S, et al.
(author)
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Ex vivo organotypic culture system of precision-cut slices of human pancreatic ductal adenocarcinoma
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 2133-
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Journal article (peer-reviewed)abstract
- Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, which is mainly due to late diagnosis and profound resistance to treatment. The latter is to a large extent attributed to the tumor stroma that is exceedingly prominent in PDAC and engages in complex interactions with the cancer cells. Hence, relevant preclinical models of PDAC should also include the tumor stroma. We herein describe the establishment and functional validation of an ex vivo organotypic culture of human PDAC that is based on precision-cut tissue slices from surgical specimens and reproducibly recapitulates the complex cellular and acellular composition of PDAC, including its microenvironment. The cancer cells, tumor microenvironment and interspersed remnants of nonneoplastic pancreas contained in these 350 µm thick slices maintained their structural integrity, phenotypic characteristics and functional activity when in culture for at least 4 days. In particular, tumor cell proliferation persisted and the grade of differentiation and morphological phenotype remained unaltered. Cultured tissue slices were metabolically active and responsive to rapamycin, an mTOR inhibitor. This culture system is to date the closest surrogate to the parent carcinoma and harbors great potential as a drug sensitivity testing system for the personalized treatment of PDAC.
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| 31. |
- Misra, Tvisha, et al.
(author)
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A genetically encoded biosensor for visualising hypoxia responses in vivo
- 2017
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In: Biology Open. - : The Company of Biologists. - 2046-6390. ; 6:2, s. 296-304
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Journal article (peer-reviewed)abstract
- Cells experience different oxygen concentrations depending on location, organismal developmental stage, and physiological or pathological conditions. Responses to reduced oxygen levels (hypoxia) rely on the conserved hypoxia-inducible factor 1 (HIF-1). Understanding the developmental and tissue-specific responses to changing oxygen levels has been limited by the lack of adequate tools for monitoring HIF-1 in vivo. To visualise and analyse HIF-1 dynamics in Drosophila, we used a hypoxia biosensor consisting of GFP fused to the oxygen-dependent degradation domain (ODD) of the HIF-1 homologue Sima. GFP-ODD responds to changing oxygen levels and to genetic manipulations of the hypoxia pathway, reflecting oxygen-dependent regulation of HIF-1 at the single-cell level. Ratiometric imaging of GFP-ODD and a red-fluorescent reference protein reveals tissue-specific differences in the cellular hypoxic status at ambient normoxia. Strikingly, cells in the larval brain show distinct hypoxic states that correlate with the distribution and relative densities of respiratory tubes. We present a set of genetic and image analysis tools that enable new approaches to map hypoxic microenvironments, to probe effects of perturbations on hypoxic signalling, and to identify new regulators of the hypoxia response.
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