Stopping Light All-Optically

We show that light pulses can be stopped and stored all-optically, with a process that involves an adiabatic and reversible pulse bandwidth compression occurring entirely in the optical domain. Such a process overcomes the fundamental bandwidth-delay constraint in optics, and can generate arbitrarily small group velocities for light pulses with a given bandwidth, without the use of any coherent or resonant light-matter interactions. We exhibit this process in optical resonator systems, where the pulse bandwidth compression is accomplished only by small refractive index modulations performed at moderate speeds. (Accepted for publication in Phys. Rev. Lett. Submitted on Sept. 10th 2003)Comment: 18 pages including 3 figures. Accepted for publication in Phys. Rev. Let

Management of pain in Fabry disease in the UK clinical setting: consensus findings from an expert Delphi panel

Background: Fabry disease is a rare, X-linked inherited lysosomal storage disorder, that manifests as a heterogeneous disease with renal, cardiac and nervous system involvement. The most common pain experienced by people with Fabry disease are episodes of neuropathic pain reported in up to 80% of classical hemizygous male patients and up to 65% of heterozygous female patients. No clear consensus exists within UK clinical practice for the assessment and management of pain in Fabry disease based on agreed clinical practice and clinical experience. Here we describe a modified Delphi initiative to establish expert consensus on management of pain in Fabry disease in the UK clinical setting. Methods: Delphi panel members were identified based on their demonstrated expertise in managing adult or paediatric patients with Fabry disease in the UK and recruited by an independent third-party administrator. Ten expert panellists agreed to participate in two survey rounds, during which they remained anonymous to each other. Circulation of the questionnaires, and collection and processing of the panel’s responses were conducted between September 2021 and December 2021. All questions required an answer. Results: The Delphi panel reached a consensus on 21 out of 41 aspects of pain assessment and management of pain in Fabry disease. These encompassed steps in the care pathway from the goals of therapy through to holistic support, including the use of gabapentin and carbamazepine as first-line analgesic medications for the treatment of neuropathic pain in Fabry disease, as well as the proactive management of symptoms of anxiety and/or depression associated with Fabry pain. Conclusions: The consensus panel outcomes reported here have highlighted strengths in current UK clinical practice, along with unmet needs for further research and agreement. This consensus is intended to prompt the next steps towards developing clinical guidelines

Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial.

Trial designThis analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.MethodsMales aged 5-18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13-17 years), renal function, and glycolipid levels (plasma, urine).ResultsPlasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m(2) (range 90.4-161.0 mL/min/1.73 m(2)) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0-27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.ConclusionsThese data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.Trial registrationClinicalTrials.gov NCT00701415

Long-term outcomes with agalsidase alfa enzyme replacement therapy: Analysis using deconstructed composite events

This is a retrospective analysis of Fabry Outcome Survey data from children/adults (n = 677) receiving agalsidase alfa enzyme replacement therapy for a median of 3 years, examining cerebrovascular, cardiac, and renal morbidity endpoints separately. Cardiac events occurred at younger ages than cerebrovascular or renal events, cerebrovascular events were more frequent in females than males, and males were more likely to experience cardiac and renal events at a younger age than females

Chapter 12 - Human settlements, infrastructure and spatial planning

Urbanization is a process that involves simultaneous transitions and transformations across multiple dimensions, including demographic, economic, and physical changes in the landscape. Each of these dimensions presents different indicators and definitions of urbanization. The chapter begins with a brief discussion of the multiple dimensions and definitions of urbanization, including implications for GHG emissions accounting, and then continues with an assessment of historical, current, and future trends across different dimensions of urbanization in the context of GHG emissions (12.2). It then discusses GHG accounting approaches and challenges specific to urban areas and human settlements. In Section 12.3, the chapter assesses the drivers of urban GHG emissions in a systemic fashion, and examines the impacts of drivers on individuals sectors as well as the interaction and interdependence of drivers. In this section, the relative magnitude of each driver's impact on urban GHG emissions is discussed both qualitatively and quantitatively, and provides the context for a more detailed assessment of how urban form and infrastructure affect urban GHG emissions (12.4). Here, the section discusses the individual urban form drivers such as density, connectivity, and land use mix, as well as their interactions with each other. Section 12.4 also examines the links between infrastructure and urban form, as well as their combined and interacting effects on GHG emissions. Section 12.5 identifies spatial planning strategies and policy instruments that can affect multiple drivers, and Section 12.6 examines the institutional, governance, and financial requirements to implement such policies. Of particular importance with regard to mitigation potential at the urban or local scale is a discussion of the geographic and administrative scales for which policies are implemented, overlapping, and / or in conflict. The chapter then identifies the scale and range of mitigation actions currently planned and / or implemented by local governments, and assesses the evidence of successful implementation of the plans, as well as barriers to further implementation (12.7). Next, the chapter discusses major co-benefits and adverse side-effects of mitigation at the local scale, including opportunities for sustainable development (12.8). The chapter concludes with a discussion of the major gaps in knowledge with respect to mitigation of climate change in urban areas (12.9)

Phylogenetic relationships of Indian caecilians (Amphibia: Gymnophiona) inferred from mitochondrial rRNA gene sequences

India has a diverse caecilian fauna, including representatives of three of the six currently recognized families, the Caeciliidae, Ichthyophiidae, the endemic Uraeotyphlidae, but previous molecular phylogenetic studies of caecilians have not included sequences for any Indian caecilians. Partial 12S and 16S mitochondrial gene sequences were obtained for a single representative of each of the caecilian families found in India and aligned against previously reported sequences for 13 caecilian species. The resulting alignment (16 taxa, 1200 sites, of which 288 cannot be aligned unambiguously) was analyzed using parsimony, maximum-likelihood, and distance methods. As judged by bootstrap proportions, decay indices, and leaf stabilities, well-supported relationships of the Indian caecilians are recovered from the alignment. The data (1) corroborate the hypothesis, based on morphology, that the Uraeotyphlidae and Ichthyophiidae are sister taxa, (2) recover a monophyletic Ichthyophiidae, including Indian and South East Asian representatives, and (3) place the Indian caeciliid Gegeneophis ramaswamii as the sister group of the caeciliid caecilians of the Seychelles. Rough estimates of divergence times suggest an origin of the Uraeotyphlidae and Ichthyophiidae while India was isolated from Laurasia and Africa and are most consistent with an Indian origin of these families and subsequent dispersal of ichthyophiids into South East Asia

Schemes of transmission of classical information via quantum channels with many senders: discrete and continuous variables cases

Superadditivity effects in the classical capacity of discrete multi-access channels (MACs) and continuous variable (CV) Gaussian MACs are analysed. New examples of the manifestation of superadditivity in the discrete case are provided including, in particular, a channel which is fully symmetric with respect to all senders. Furthermore, we consider a class of channels for which {\it input entanglement across more than two copies of the channels is necessary} to saturate the asymptotic rate of transmission from one of the senders to the receiver. The 5-input entanglement of Shor error correction codewords surpass the capacity attainable by using arbitrary two-input entanglement for these channels. In the CV case, we consider the properties of the two channels (a beam-splitter channel and a "non-demolition" XP gate channel) analyzed in [Czekaj {\it et al.}, Phys. Rev. A {\bf 82}, 020302 (R) (2010)] in greater detail and also consider the sensitivity of capacity superadditivity effects to thermal noise. We observe that the estimates of amount of two-mode squeezing required to achieve capacity superadditivity are more optimistic than previously reported.Comment: 19 pages, 11 figure

Scleroderma with crescentic glomerulonephritis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Systemic sclerosis or scleroderma is an autoimmune rheumatic disease characterized by organ-based fibrosis. Renal involvement in scleroderma occurs mainly in the form of scleroderma renal crisis, affecting 5 to 10% of patients. It remains one of the most important and immediately life-threatening complications of scleroderma, but the prognosis improves considerably after treatment with angiotensin-converting enzyme inhibitors. Other renal pathologies can occur in scleroderma. These include scleroderma overlap syndromes with associated features of lupus nephritis, myeloperoxidase anti-neutrophil cytoplasmic antibodies (ANCA) or proteinase 3 ANCA-associated glomerulonephritis, or crescentic glomerulonephritis. These alternative pathologies should be suspected in any individual patient with a differing clinical picture and the patient should be appropriately investigated. Crescentic glomerulonephritis occurs very rarely in scleroderma. This report describes a patient with scleroderma and crescentic glomerulonephritis.</p> <p>Case presentation</p> <p>A 52-year-old woman with a known history of scleroderma and hypertension on angiotensin-converting enzyme inhibitors was referred to the nephrologist because of a rapid decline in renal function. Kidney biopsy was performed which revealed immune complex type crescentic glomrulonephritis. Cytoplasmic-staining ANCA was negative. Despite immunosuppressive treatment the patient rapidly went into end-stage renal failure and is still on hemodialysis.</p> <p>Conclusion</p> <p>Scleroderma is a complex disease, and the best characterized renal involvement in scleroderma is scleroderma renal crisis. However, other renal pathologies can occur in scleroderma. These alternative pathologies should be suspected in any patient with a differing clinical picture and the patient should be appropriately investigated, as the clinical course and treatment are different from the more common scleroderma renal crisis.</p

Twenty years of the Fabry Outcome Survey (FOS) : insights, achievements, and lessons learned from a global patient registry

Background: Patient registries provide long-term, real-world evidence that aids the understanding of the natural history and progression of disease, and the efects of treatment on large patient populations with rare diseases. The year 2021 marks the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The primary aims of FOS are to broaden the understanding of Fabry disease (FD), an X-linked lysosomal storage disorder, and to improve the clinical management of afected patients. Here, we review the history of FOS and the analyses and publications disseminated from the registry, and we discuss the contributions FOS stud‑ ies have made in understanding FD. Results: FOS was initiated in April 2001 and, as of January 2021, 4484 patients with a confrmed diagnosis and patient informed consent have been enrolled from 144 centers across 26 countries. Data from FOS have been pub‑ lished in nearly 60 manuscripts on a wide variety of topics relevant to FD. Analyses of FOS data have investigated the long-term efectiveness and safety of enzyme replacement therapy (ERT) with agalsidase alfa and its efects on morbidity and mortality, as well as the benefts of prompt and early treatment with agalsidase alfa on the progression of cardiomyopathy and the decline in renal function associated with FD. Based on analyses of FOS data, ERT with agal‑ sidase alfa has also been shown to improve additional signs and symptoms of FD experienced by patients. FOS data analyses have provided a better understanding of the natural history of FD and the specifc populations of women, children, and the elderly, and have provided practical tools for the study of FD. FOS has also provided methodology and criteria for assessing disease severity which contributed to the continuous development of medical practice in FD and has largely improved our understanding of the challenges and needs of long-term data collection in rare diseases, aiding in future rare disease real-world evidence studies. Conclusion: FOS over the last 20 years has substantially increased the scientifc knowledge around improved patient management of FD and continues to expand our understanding of this rare disease