International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease.

Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, an international working group of 42 experts from 10 countries was convened to establish consensus recommendations based on review of treatment in published cases of UCD, the CDCN ACCELERATE registry, and expert opinion. Complete surgical resection is often curative and is therefore the preferred first-line therapy, if possible. The management of unresectable UCD is more challenging. Existing evidence supports that asymptomatic unresectable UCD may be observed. The anti-interleukin-6 monoclonal antibody siltuximab should be considered for unresectable UCD patients with an inflammatory syndrome. Unresectable UCD that is symptomatic as a result of compression of vital neighboring structures may be rendered amenable to resection by medical therapy (eg, rituximab, steroids), radiotherapy, or embolization. Further research is needed in UCD patients with persisting constitutional symptoms despite complete excision and normal laboratory markers. We hope that these guidelines will improve outcomes in UCD and help treating physicians decide the best therapeutic approach for their patients

Coulomb dissociation of O-16 into He-4 and C-12

We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4

The bassoon in Australia : repertoire and contemporary relevance

This project attempts to assess and predict the future of the bassoon in Australia. This must be contextualised within the future of classical music in general. Classical music has a long history, its antecedents stemming from the liturgical and secular music of the Medieval and Renaissance periods. The Classical and Romantic periods of the eighteenth and nineteenth centuries established what some regard as a set or standard identity for classical music; however, various forces combine to destabilise this standard and drive the classical genre to evolve in order to maintain relevance. In the past several decades, scholars, reviewers and those in the industry have referred to a crisis in classical music. This crisis is the result of the movement of attention and education away from classical and toward popular music; the structure of the music recording marketing industry which has, over an extensive period, virtually prohibited the entry of obscure or innovative music into mass markets; and the perception that the enjoyment of classical music is somehow a specialised, possibly elitist skill and one that is not suited or accessible to the mass audience. Given that much of the long term viability of an art form depends on its success in the market and its ability to connect with audiences, overcoming these barriers to the accessibly and enjoyment of classical music is regarded as key to its very survival. However, with the current changes in technology and marketing structures, it is possible for the current crisis to be regarded as a significant opportunity for further growth of the classical repertoire and the market for it. In fact the long term viability and survival of classical music, and therefore of the bassoon, may depend on the ability of those in the field to understand the current challenges and opportunities. By adopting mixed methodologies which include an analysis of literature, a pedagogical survey involving aspects of practice-based research and empirical research, the thesis examines the existing Australian bassoon repertoire and the views of those deeply involved in playing, composing for, and promoting the bassoon on the Australian music scene. Following qualitative interviews with bassoonists, composers and classical music marketers, it is observed that the bassoon has several special challenges. It is an instrument which has sometimes been overlooked or poorly recognised, and whose unique sounds and abilities have often been used in a comic way, resulting in its stereotyping as the 'clown of the orchestra'. It presents a physical challenge because of its weight and dimensions, it is expensive and the repertoire that currently exists in Australia is limited, a fact demonstrated by the pedagogical survey. The thesis seeks ways of resolving or working with these challenges. However, the potential of the bassoon to build a relevant contemporary identity both through traditional and extended techniques used in composition and the extension of repertoire is profound. Coupled with and extending the pedagogical survey was the commissioning and recording of a CD sampler of new and previously unrecorded contemporary classical bassoon music, also involving practice-led research. The pieces recorded on the CD are an attempt to respond to the strengths and weaknesses identified through other research in the thesis in relation to compositional style and variety. It also serves as a means of seeking responses from marketers of classical CDs. The production of the CD demonstrates what can be accomplished when composers are commissioned to write new pieces, how these add to the repertoire and how such repertoire might be marketed. It also requires an active ideological, musical and spoken dialogue between composers and performers presenting new, relevant repertoire as well as pieces not previously recorded. In doing so, the CD represents one of several ways in which the bassoon can continue to be relevant to the contemporary Australian audience

Conserving Tropical Forests: Can Sustainable Livelihoods Outperform Artisanal or Informal Mining?

The viability of conservation efforts, including protected areas and buffer zones, depends on finding ways to make those strategies more attractive and viable for local populations. This paper presents a pilot study utilizing a rapid rural appraisal of livelihoods in the buffer zone of Tambopata National Reserve in Madre de Dios, Peru, threatened by illegal gold mining and logging. We evaluated three predominant economic activities—artisanal gold mining, Brazil nut harvesting, and fish farming—in terms of potential economic returns. The main research question we ask is whether the latter two potentially sustainable land uses can match or exceed the returns from mining. Contrary to popular belief, we find that enhancing value creation at product origin could make existing forest-friendly livelihoods as or more lucrative than extractive ones. This has implications on local conservation policy encouraging implementable strategies incentivizing sustainable livelihoods in tandem with, and in support of, conservation goals

Understanding Environmental, Health and Economic Activity Interactions Following Transition of Ownership in Gold Mining Areas in Tanzania: A Case of Private to Public

Mining is an important source of revenue for many developing countries, however, the social, environmental and economic impacts of mining are often poorly monitored. The recent transition of a gold mine in Western Tanzania—from large-scale gold mine under private, multinational ownership, to medium-scale public and national owned mine with limited life length offers a prime opportunity to understand the implications of changes in ownership and scale on the local economy and community well-being. We conducted 44 semi-structured interviews with community members in four villages adjacent to the mine site. We find that the local economy and public service provision contracted in response to the mine transition and downscaling, with ramifications for food security and healthcare access. Community members also highlighted the lack of information surrounding the mine transformation. This illustrates that considering the post-transition phase of large-scale mines is important for providing long run sustainable livelihood strategies in mining communities

Understanding Environmental, Health and Economic Activity Interactions Following Transition of Ownership in Gold Mining Areas in Tanzania: A Case of Private to Public

Mining is an important source of revenue for many developing countries, however, the social, environmental and economic impacts of mining are often poorly monitored. The recent transition of a gold mine in Western Tanzania—from large-scale gold mine under private, multinational ownership, to medium-scale public and national owned mine with limited life length offers a prime opportunity to understand the implications of changes in ownership and scale on the local economy and community well-being. We conducted 44 semi-structured interviews with community members in four villages adjacent to the mine site. We find that the local economy and public service provision contracted in response to the mine transition and downscaling, with ramifications for food security and healthcare access. Community members also highlighted the lack of information surrounding the mine transformation. This illustrates that considering the post-transition phase of large-scale mines is important for providing long run sustainable livelihood strategies in mining communities

Differences in complications, cardiovascular risk factor, and diabetes management among participants enrolled at veterans affairs (VA) and non-VA medical centers in the glycemia reduction approaches in diabetes: A comparative effectiveness study (GRADE)

Aims: We evaluated differences in participants with type 2 diabetes (T2DM) enrolled in the GRADE study at VA vs non-VA sites, focusing on cardiovascular risk factors and rates of diabetes care target achievements. Methods: We compared baseline characteristics between participants at VA (n = 1216) and non-VA (n = 3831) sites, stratifying analyses by cardiovascular disease (CVD) history. Results: VA and non-VA participants had similar diabetes duration (4.0 years), HbA1c (7.5%), and BMI (34 kg/m2); however, VA participants had more individuals ≥ 65 years (37.3% vs 19.8%, p \u3c 0.001), men (90.0% vs 55.2%, p \u3c 0.001), hypertension (75.8% vs 63.6%, p \u3c 0.001), hyperlipidemia (76.6% vs 64.6%, p \u3c 0.001), current smokers (19.0% vs 12.1%, p \u3c 0.001), nephropathy (20.4% vs 17.0%, p \u3c 0.05), albuminuria (18.4% vs 15.1%, p \u3c 0.05), and CVD (10.4% vs 5.2%, p \u3c 0.001). In those without CVD, more VA participants were treated with lipid (70.8% vs 59.5%, p \u3c 0.001) and blood pressure (74.9% vs 65.4%, p \u3c 0.001) lowering medications, and had LDL-C \u3c 70 mg/dl (32.9% vs 24.2%, p \u3c 0.05). Among those with CVD, more VA participants had BP \u3c 140/90 (80.2% vs 70.1%, p \u3c 0.05) after adjusting for demographics. Conclusion: GRADE participants at VA sites had more T2DM complications, greater CVD risk and were more likely to be treated with medications to reduce it, leading to more LDL-C at goal than non-VA participants, highlighting differences in diabetes populations and care

Discovery and validation of a novel subgroup and therapeutic target in idiopathic multicentric Castleman disease

Abstract Idiopathic multicentric Castleman disease (iMCD) is a poorly understood hematologic disorder involving cytokine-induced polyclonal lymphoproliferation, systemic inflammation, and potentially fatal multiorgan failure. Although the etiology of iMCD is unknown, interleukin-6 (IL-6) is an established disease driver in approximately one-third of patients. Anti–IL-6 therapy, siltuximab, is the only US Food and Drug Administration–approved treatment. Few options exist for siltuximab nonresponders, and no validated tests are available to predict likelihood of response. We procured and analyzed the largest-to-date cohort of iMCD samples, which enabled classification of iMCD into disease categories, discovery of siltuximab response biomarkers, and identification of therapeutic targets for siltuximab nonresponders. Proteomic quantification of 1178 analytes was performed on serum of 88 iMCD patients, 60 patients with clinico-pathologically overlapping diseases (human herpesvirus-8–associated MCD, N = 20; Hodgkin lymphoma, N = 20; rheumatoid arthritis, N = 20), and 42 healthy controls. Unsupervised clustering revealed iMCD patients have heterogeneous serum proteomes that did not cluster with clinico-pathologically overlapping diseases. Clustering of iMCD patients identified a novel subgroup with superior response to siltuximab, which was validated using a 7-analyte panel (apolipoprotein E, amphiregulin, serum amyloid P-component, inactivated complement C3b, immunoglobulin E, IL-6, erythropoietin) in an independent cohort. Enrichment analyses and immunohistochemistry identified Janus kinase (JAK)/signal transducer and activator of transcription 3 signaling as a candidate therapeutic target that could potentially be targeted with JAK inhibitors in siltuximab nonresponders. Our discoveries demonstrate the potential for accelerating discoveries for rare diseases through multistakeholder collaboration