Migration in Arctic Alaska: Empirical Evidence of the Stepping Stones Hypothesis

This paper explores hypotheses of hierarchical migration using data from the Alaskan Arctic. We focus on migration of Iñupiat people, who are indigenous to the region, and explore the role of income and subsistence harvests on migration. To test related hypotheses we use confidential micro-data from the US Census Bureau’s 2000 Decennial Census of Population and Income and generate migration probabilities using a mixed multinomial and conditional logit model. Our findings are broadly consistent with Ravenstein’s (1885) early hypothesis of step-wise migration; we find evidence of step-wise migration, both up and down an urban and rural hierarchy. We also find that where migrants choose to live is a function of place, personal, and household characteristics.Migration, Hierarchical Migration, Rural to Urban Migration, Arctic Alaska

Novel Approaches Towards a Functional Cure of HIV/AIDS

Altres ajuts: The present work was funded in parts by NIH Grant P01-AI131568Therapeutic approaches towards a functional cure or eradication of HIV have gained renewed momentum upon encouraging data emerging from studies in SIV monkey models and recent results from human clinical studies. However, a multitude of questions remain to be addressed, including how to deal with the latent viral reservoir, how to boost the host immune response to the virus and what the hurdles are to reach relevant viral compartments in the body. Advances have been made especially with regard to identifying agents that can reactivate the latent virus in vivo and boost the cellular and humoral immunity, but it remains largely unclear whether any of these strategies can awaken a sufficiently large fraction of the viral reservoir and whether the boosted immunity can prevent rapid viral replication once antiretroviral treatments are stopped

Treatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors

Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. Here we examined the effect of patiromer treatment on serum aldosterone, blood pressure, and albuminuria in patients with chronic kidney disease on renin-angiotensin system inhibitors with hyperkalemia (serum potassium 5.1–6.5 mEq/l). We analyzed data from the phase 3 OPAL-HK study (4-week initial treatment phase of 243 patients; 8-week randomized withdrawal phase of 107 patients). In the treatment phase, the (mean ± standard error) serum potassium was decreased concordantly with the serum aldosterone (−1.99 ± 0.51 ng/dl), systolic/diastolic blood pressure (−5.64 ± 1.04 mm Hg/−3.84 ± 0.69 mm Hg), and albumin-to-creatinine ratio (−203.7 ± 54.7 mg/g), all in a statistically significant manner. The change in the plasma renin activity (−0.44 ± 0.63 μg/l/hr) was not significant. In the withdrawal phase, mean aldosterone levels were sustained with patiromer (+0.23 ± 1.07 ng/dl) and significantly increased with placebo (+2.78 ± 1.25 ng/dl). Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (−6.70 ± 1.59/−2.15 ± 1.06 mm Hg), whereas those on placebo did not (−1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (–3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors

Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on RAAS inhibitors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115921/1/ejhf402_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/115921/2/ejhf402.pd

Long‐term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin‐converting enzymes/angiotensin receptor blockers: results from AMETHYST‐DN

AimsChronic kidney disease (CKD) in heart failure (HF) increases the risk of hyperkalaemia (HK), limiting angiotensin‐converting enzyme inhibitor (ACE‐I) or angiotensin receptor blocker (ARB) use. Patiromer is a sodium‐free, non‐absorbed potassium binder approved for HK treatment. We retrospectively evaluated patiromer’s long‐term safety and efficacy in HF patients from AMETHYST‐DN.Methods and resultsPatients with Type 2 diabetes, CKD, and HK [baseline serum potassium >5.0–5.5 mmol/L (mild) or >5.5–88%) and moderate (≥73%) HK had normokalaemia at each visit from Weeks 12 to 52. Three HF patients were withdrawn because of high (n = 1) or low (n = 2) serum potassium. The most common patiromer‐related adverse event was hypomagnesaemia (8.6%).ConclusionsIn patients with a clinical diagnosis of HF, diabetes, CKD, and HK on ACE‐I/ARB, patiromer was well tolerated and effective for HK treatment over 52 weeks.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145406/1/ehf212292.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145406/2/ehf212292_am.pd

Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia

Patients with chronic kidney disease (CKD) have a high risk of hyperkalemia, which increases mortality and can lead to renin–angiotensin–aldosterone system inhibitor (RAASi) dose reduction or discontinuation. Patiromer, a nonabsorbed potassium binder, has been shown to normalize serum potassium in patients with CKD and hyperkalemia on RAASi. Here, patiromer's onset of action was determined in patients with CKD and hyperkalemia taking at least one RAASi. After a 3-day potassium- and sodium-restricted diet in an inpatient research unit, those with sustained hyperkalemia (serum potassium 5.5 – under 6.5 mEq/l) received patiromer 8.4 g/dose with morning and evening meals for a total of four doses. Serum potassium was assessed at baseline (0 h), 4 h postdose, then every 2–4 h to 48 h, at 58 h, and during outpatient follow-up. Mean baseline serum potassium was 5.93 mEq/l and was significantly reduced by 7 h after the first dose and at all subsequent times through 48 h. Significantly, mean serum potassium under 5.5 mEq/l was achieved within 20 h. At 48 h (14 h after last dose), there was a significant mean reduction of 0.75 mEq/l. Serum potassium did not increase before the next dose or for 24 h after the last dose. Patiromer was well tolerated, without serious adverse events and no withdrawals. The most common gastrointestinal adverse event was mild constipation in two patients. No hypokalemia (serum potassium under 3.5 mEq/l) was observed. Thus, patiromer induced an early and sustained reduction in serum potassium and was well tolerated in patients with CKD and sustained hyperkalemia on RAASis

Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening

The first crystal structure is reported of a glutaryl-CoA dehydrogenase in the apo state without flavin adenine dinucleotide cofactor bound. Additional structures with small molecules complexed in the catalytic active site were obtained by fragment-based screening

The Protein Maker: an automated system for high-throughput parallel purification

The Protein Maker instrument addresses a critical bottleneck in structural genomics by allowing automated purification and buffer testing of multiple protein targets in parallel with a single instrument. Here, the use of this instrument to (i) purify multiple influenza-virus proteins in parallel for crystallization trials and (ii) identify optimal lysis-buffer conditions prior to large-scale protein purification is described

Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from Babesia bovis

Structural characterization of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from B. bovis in the apo state and complexed with antifolate inhibitors in both enzymatic active sites is reported

Energy injustice and Nordic electric mobility: inequality, elitism, and externalities in the electrification of vehicle-to-grid (V2G) transport

Much research on electric mobility transitions has been descriptive or positive, rather than normative or critical, assessing the deeper ethical, justice, or moral issues that arise. To address this gap, this study qualitatively assesses the ongoing transition to Nordic electric vehicles (EVs) and vehicle-to-grid (V2G) systems. It does so through the various lenses of distributive justice, procedural justice, cosmopolitan justice, and recognition justice. It asks: what are the types of injustices associated with electric mobility and V2G? In what ways do emerging patterns of electric mobility worsen socio-environmental risks or vulnerabilities? Based on original primary data collected from 257 experts across Denmark, Finland, Iceland, Norway, and Sweden, the study finds that electric mobility can erode elements of distributive justice for being accessible only to the rich, and for raising risks related to privacy, hacking, and cyberterrorism. Electric mobility may contravene aspects of procedural justice by reinforcing exclusion and elitism in national planning. It can erode cosmopolitan justice by producing negative environmental externalities, and exacerbating rural (and global) vulnerability. It may threaten recognition justice through unemployment, disruption to traditional businesses, and the entrenchment of patriarchy. Thankfully, the study also proposes a suite of policy mechanisms to address many of these concerns