The sustainability agenda has evolved around a set of interconnected dilemmas regarding economic, social, and environmental goals. Progress has been made in establishing thresholds and targets that ...must be achieved to enable life to continue to thrive on the planet. However, much work remains to be done in articulating coherent theoretical frameworks that adequately describe the mechanisms through which sustainability outcomes are achieved. This paper reviews core concepts in the sustainability agenda to develop four propositions on integrated sustainability that collectively describe the underlying mechanisms of sustainable development. We then advance a framework for integrated sustainability and assess its viability through linear regression and principal components analysis of key selected indicators. The results provide preliminary evidence that countries with institutions that enable cooperation and regulate competition perform better in attaining integrated sustainability indicators. Our findings suggest that institutional design is important to sustainability outcomes and that further research into process-oriented mechanisms and institutional characteristics can yield substantial dividends in enabling effective sustainability policy.
Developed organizations have increasingly garnered numerous indicators to measure gender and development outcomes. Yet, measurements themselves reflect a logic of the arenas where development occurs ...and can be captured, and therefore reflect where women are imagined to predominantly exist. Based on the analysis of 1,298 indicators across 15 major development databases covering African countries, this article argues that mainstream development organizations predominantly understand gender in terms of institutional sites. Sometimes these were sites for intervention, or a place for institutional ‘betterment’ (a hospital, a work place, and a school). Other times, these sites were conceptualized as natural places where women would be (the family and the nation state). We identify the spatial logics underpinning these development indicators, and link them to larger historical gendered and racialized colonial logics organizing diverse social, economic, and cultural lives, where economic and institutional sites are promoted, a more nuanced and relational one is displaced. Ultimately, these spatial imaginings extend to the larger context of where debates about peace and security are situated—namely in largely individual, state-driven, and institutional-centric ways.
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.
Given the linkages between natural resources and social conflicts, evidence increasingly shows that successful natural resource management requires conflict mitigation and prevention. However, there ...may be a gap in practice between knowing what processes and tools need to be used to manage conservation conflicts and how to actually implement them. We present learning from a practice-based case study of conflict management in the Amarakaeri Communal Reserve in the Peruvian Amazon that aimed to develop natural resource governance institutions and build stakeholder capacity, including of indigenous groups, to navigate existing conflict resolution mechanisms. Through applying good practices in conservation conflict management and collaborative governance, we generated important lessons on the practical considerations involved in collaborative conservation. These lessons, while specific to our case, could be applied to a variety of protected areas facing complex social-ecological systems dynamics and wicked problems.
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.
Uremic symptoms, including fatigue, anorexia, pruritus, nausea, paresthesia, and pain, are attributed to the accumulation of organic waste products normally cleared by the kidneys, but whether kidney ...function is the primary driver of changes in symptom severity over time is not known. The goal of our study was to evaluate the association between eGFR and uremic symptom severity score in patients with CKD.
We identified 3685 participants with CKD not on dialysis in the prospective, observational Chronic Renal Insufficiency Cohort (CRIC) Study with baseline assessment of eGFR and uremic symptom severity. Symptoms were assessed by separate questions on the Kidney Disease Quality of Life-36 instrument (zero- to 100-point scale). The longitudinal association between eGFR and uremic symptom severity score was examined with multivariable adjusted linear mixed-effects models with random intercepts and random slopes.
The mean±SD eGFR at baseline was 44±15 ml/min per 1.73 m
, and participants had a median of six (interquartile range 3-11) simultaneous assessments of eGFR and uremic symptoms over the duration of follow-up. The most prevalent symptoms at baseline were pain (57%), fatigue (52%), paresthesia (45%), and pruritus (42%). In adjusted models, a decrease in eGFR of 5 ml/min per 1.73 m
was associated with a worsening of the symptom severity score by two points or less for each uremic symptom (
<0.01; zero- to 100-point scale). The association between eGFR and uremic symptom severity score was nonlinear. When starting from a lower initial eGFR, a 5 ml/min per 1.73 m
decrease in eGFR was associated with a greater magnitude of uremic symptom worsening.
The prevalence of uremic symptoms in CKD is high, with significant variability in patient symptom change over time. Declines in eGFR were associated with worsening of uremic symptom severity, but the magnitude of these changes is small and of uncertain clinical significance.
Protein carbamylation, a nonenzymatic post-translational protein modification partially driven by elevated blood urea levels, associates with mortality and adverse outcomes in patients with ESKD on ...dialysis. However, little is known about carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. In this prospective observational cohort study of 3111 individuals with CKD stages 2-4, higher levels of carbamylated albumin (a marker of protein carbamylation burden) were associated with a greater risk of developing ESKD and other significant adverse clinical outcomes. These findings indicate that protein carbamylation is an independent risk factor for CKD progression. They suggest that further study of therapeutic interventions to prevent or reduce carbamylation is warranted.
Protein carbamylation, a post-translational protein modification partially driven by elevated blood urea levels, associates with adverse outcomes in ESKD. However, little is known about protein carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD.
To test associations between protein carbamylation and the primary outcome of progression to ESKD, we measured baseline serum carbamylated albumin (C-Alb) in 3111 patients with CKD stages 2-4 enrolled in the prospective observational Chronic Renal Insufficiency Cohort study.
The mean age of study participants was 59 years (SD 10.8); 1358 (43.7%) were female, and 1334 (42.9%) were White. The mean eGFR at the time of C-Alb assessment was 41.8 (16.4) ml/minute per 1.73 m 2 , and the median C-Alb value was 7.8 mmol/mol (interquartile range, 5.8-10.7). During an average of 7.9 (4.1) years of follow-up, 981 (31.5%) individuals developed ESKD. In multivariable adjusted Cox models, higher C-Alb (continuous or quartiles) independently associated with an increased risk of ESKD. For example, compared with quartile 1 (C-Alb ≤5.80 mmol/mol), those in quartile 4 (C-Alb >10.71 mmol/mol) had a greater risk for ESKD (adjusted hazard ratio, 2.29; 95% confidence interval, 1.75 to 2.99), and the ESKD incidence rate per 1000 patient-years increased from 15.7 to 88.5 from quartile 1 to quartile 4. The results remained significant across numerous subgroup analyses, when treating death as a competing event, and using different assessments of eGFR.
Having a higher level of protein carbamylation as measured by circulating C-Alb is an independent risk factor for ESKD in individuals with CKD stages 2-4.
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_04_24_JSN_URE_EP22_042423.mp3.
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.
•Clustering analysis from proteomic quantification of iMCD serum identified a novel subgroup with superior siltuximab response.•Enrichment analyses and immunohistochemistry identified JAK-STAT3 signaling as a candidate therapeutic target in iMCD.
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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.
•The preferred therapy for UCD is complete surgical resection.•Unresectable asymptomatic UCD may be observed; symptomatic UCD requires rituximab ± steroids or anti–interleukin-6 antibody.
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