Brans-Dicke Theory and primordial black holes in Early Matter-Dominated Era

We show that primordial black holes can be formed in the matter-dominated era with gravity described by the Brans-Dicke theory. Considering an early matter-dominated era between inflation and reheating, we found that the primordial black holes formed during that era evaporate at a quicker than those of early radiation-dominated era. Thus, in comparison with latter case, less number of primordial black holes could exist today. Again the constraints on primordial black hole formation tend towards the larger value than their radiation-dominated era counterparts indicating a significant enhancement in the formation of primordial black holes during the matter-dominaed era.Comment: 9 page

Constraints on the mass spectrum of primordial black holes and braneworld parameters from the high-energy diffuse photon background

We investigate the spectral shape of a high-energy diffuse photon emitted by evaporating primordial black holes (PBHs) in the Randall-Sundrum type II (RS2) braneworld. In their braneworld scenario, the nature of small PBHs is drastically modified from the ordinary four-dimensional case for the following two reasons. (i) dropping Hawking temperature, which equivalently lengthens the lifetime of the individual PBH due to the change of space-time topology and (ii) the effective increase of the total amount of PBHs caused by accretion during the earliest part of the radiation-dominated epoch, the brane high-energy phase. From studies of the expected spectral shape and its dependence on braneworld parameters, we obtain two qualitatively distinctive possibilities of constraints on the braneworld PBHs from the observations of diffuse high-energy photon background. If the efficiency of accretion in the high-energy phase exceeds a critical value, the existence of the extra dimension gives a more stringent upper bound on the abundance of PBHs than the 4D case and a small length scale for the extra dimension is favored. On the contrary, in the case below the critical accretion efficiency, we find that the constraint on the PBH abundance can be relaxed by a few orders of magnitude in exchange for the existence of the large extra dimension; its size may be even bounded in the region above 10^{19} times 4D Planck length scale provided the rest mass energy density of the PBHs relative to energy density of radiation is actually larger than 10^{-27} (4D upper bound) at their formation time. The above analytical studies are also confirmed numerically, and an allowed region for braneworld parameters and PBH abundance is clearly obtained.Comment: 16 pages, 8 figures, REVTeX4; version published in PR

Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease

BACKGROUND: In a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, >/=60 ml per minute), the vasopressin V2-receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODS: We conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient's ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m(2) of body-surface area or 56 to 65 years of age with an estimated GFR of 25 to 44 ml per minute per 1.73 m(2) were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. RESULTS: The change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m(2) (95% confidence interval [CI], -2.81 to -1.87) in the tolvaptan group, as compared with -3.61 ml per minute per 1.73 m(2) (95% CI, -4.08 to -3.14) in the placebo group (difference, 1.27 ml per minute per 1.73 m(2); 95% CI, 0.86 to 1.68; P3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. CONCLUSIONS: Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145 .)

Polar lessons learned: long-term management based on shared threats in Arctic and Antarctic environments

The Arctic and Antarctic polar regions are subject to multiple environmental threats, arising from both local and ex-situ human activities. We review the major threats to polar ecosystems including the principal stressor, climate change, which interacts with and exacerbates other threats such as pollution, fisheries overexploitation, and the establishment and spread of invasive species. Given the lack of progress in reducing global atmospheric greenhouse-gas emissions, we suggest that managing the threats that interact synergistically with climate change, and that are potentially more tractable, is all the more important in the short to medium term for polar conservation. We show how evidence-based lessons learned from scientific research can be shared between the poles on topics such as contaminant mitigation, biosecurity protocols to reduce species invasions, and the regulation of fisheries and marine environments. Applying these trans-polar lessons in tandem with expansion of international cooperation could substantially improve environmental management in both the Arctic and Antarctic

PowerPoint Slides for: Rationale and Design of a Clinical Trial Investigating Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease

<p><b><i>Background:</i></b> In TEMPO 3:4, the vasopressin V2-receptor antagonist tolvaptan slowed kidney growth and function decline in autosomal dominant polycystic kidney disease (ADPKD) patients with relatively preserved kidney function. <b><i>Methods:</i></b> Prospective, phase 3b, multi-center, randomized-withdrawal, placebo-controlled, double-blind trial of tolvaptan in ADPKD patients with late stage 2 to early stage 4 chronic kidney disease (CKD). The primary endpoint was estimated glomerular filtration rate (eGFR) change from pre-treatment baseline to post-treatment follow-up. Secondary endpoints included annualized eGFR slope, incidence of ADPKD complications, and overall and hepatic safety profiles. Participants were 18-55 year-old ADPKD patients with baseline eGFR ≥25 and ≤65 mL/min/1.73 m² or 56-65 year-old with eGFR ≥25 and ≤44 mL/min/1.73 m² and evidence of eGFR decline >2.0 mL/min/1.73 m² per year. Daily split doses of tolvaptan were titrated to tolerance (30/15, 45/15, 60/30, or 90/30 mg) and maintained for 12 months, after an 8-week pre-randomization period to screen out subjects unable to tolerate at least 60/30 mg for 3 weeks. <b><i>Results:</i></b> Of 1,495 subjects who entered the tolvaptan titration period, 125 (8.4%) discontinued the study before randomization. One thousand three hundred seventy subjects (684 tolvaptan, 686 placebo) from 213 centers across 21 countries were randomized. Baseline demographics were well balanced across treatment arms. Information collected during the study included eGFR, survey scores (PKD history and outcome), adverse events, vital signs, hematology, urinalysis, and serum chemistry tests. <b><i>Conclusion:</i></b> Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy (REPRISE) determines whether tolvaptan administered over 1 year exhibits disease-modifying properties in ADPKD patients with late stage 2 to early stage 4 CKD, which provides an important therapeutic advancement for this difficult-to-treat disease.</p