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Aircraft carriers
Text and photographs take readers on a tour of an aircraft carrier from the control tower down to the nuclear engine room.
Book
Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study
Alagille syndrome is a rare genetic disease that often presents with severe cholestasis and pruritus. There are no approved drugs for management. Maralixibat, an apical, sodium-dependent, bile acid transport inhibitor, prevents enterohepatic bile acid recirculation. We evaluated the safety and efficacy of maralixibat for children with cholestasis in Alagille syndrome.
ICONIC was a placebo-controlled, randomised withdrawal period (RWD), phase 2b study with open-label extension in children (aged 1–18 years) with Alagille syndrome (NCT02160782). Eligible participants had more than three times the normal serum bile acid (sBA) levels and intractable pruritus. After 18 weeks of maralixibat 380 μg/kg once per day, participants were randomly assigned (1:1) to continue maralixibat or receive placebo for 4 weeks. Subsequently, all participants received open-label maralixibat until week 48. During the long-term extension (204 weeks reported), doses were increased up to 380 μg/kg twice per day. The primary endpoint was the mean sBA change during the RWD in participants with at least 50% sBA reduction by week 18. Cholestastic pruritus was assessed using observer-rated, patient-rated, and clinician-rated 0–4 scales. The safety population was defined as all participants who had received at least one dose of maralixibat. This trial was registered with ClinicalTrials.gov, NCT02160782, and is closed to recruitment.
Between Oct 28, 2014, and Aug 14, 2015, 31 participants (mean age 5·4 years [SD 4·25]) were enrolled and 28 analysed at week 48. Of the 29 participants who entered the randomised drug withdrawal period, ten (34%) were female and 19 (66%) were male. In the RWD, participants switched to placebo had significant increases in sBA (94 μmol/L, 95% CI 23 to 164) and pruritus (1·7 points, 95% CI 1·2 to 2·2), whereas participants who continued maralixibat maintained treatment effect. This study met the primary endpoint (least square mean difference –117 μmol/L, 95% CI –232 to –2). From baseline to week 48, sBA (–96 μmol/L, –162 to –31) and pruritus (–1·6 pts, –2·1 to –1·1) improved. In participants who continued to week 204 (n=15) all improvements were maintained. Maralixibat was generally safe and well tolerated throughout. The most frequent adverse events were gastrointestinal related. Most adverse events were self-limiting in nature and mild-to-moderate in severity.
In children with Alagille syndrome, maralixibat is, to our knowledge, the first agent to show durable and clinically meaningful improvements in cholestasis. Maralixibat might represent a new treatment paradigm for chronic cholestasis in Alagille syndrome.
Mirum Pharmaceuticals.
Journal Article
Fractional Doses of Pneumococcal Conjugate Vaccine — A Noninferiority Trial
Pneumococcal conjugate vaccines are an important but costly part of childhood vaccination. This trial assessed immunogenicity of fractional-dose regimens — a key consideration as countries transition out of Gavi support.
Journal Article
Self-assembled micellar nanocomplexes comprising green tea catechin derivatives and protein drugs for cancer therapy
A green tea-based drug carrier offers a delivery system where both the drug and carrier possess therapeutic effects.
When designing drug carriers, the drug-to-carrier ratio is an important consideration, because the use of high quantities of carriers can result in toxicity as a consequence of poor metabolism and elimination of the carriers
1
. However, these issues would be of less concern if both the drug and carrier had therapeutic effects. (−)-Epigallocatechin-3-
O
-gallate (EGCG), a major ingredient of green tea, has been shown, for example, to possess anticancer effects
2
,
3
,
4
,
5
,
6
,
7
, anti-HIV effects
8
, neuroprotective effects
9
and DNA-protective effects
10
. Here, we show that sequential self-assembly of the EGCG derivative with anticancer proteins leads to the formation of stable micellar nanocomplexes, which have greater anticancer effects
in vitro
and
in vivo
than the free protein. The micellar nanocomplex is obtained by complexation of oligomerized EGCG with the anticancer protein Herceptin to form the core, followed by complexation of poly(ethylene glycol)–EGCG to form the shell. When injected into mice, the Herceptin-loaded micellar nanocomplex demonstrates better tumour selectivity and growth reduction, as well as longer blood half-life, than free Herceptin.
Journal Article
Aircraft carriers
This book teaches readers about aircraft carriers from their function in the military to the crew that serves on them.
Book
Enhanced charge carrier transport and defects mitigation of passivation layer for efficient perovskite solar cells
Surface passivation has been developed as an effective strategy to reduce trap-state density and suppress non-radiation recombination process in perovskite solar cells. However, passivation agents usually own poor conductivity and hold negative impact on the charge carrier transport in device. Here, we report a binary and synergistical post-treatment method by blending 4-
tert
-butyl-benzylammonium iodide with phenylpropylammonium iodide and spin-coating on perovskite surface to form passivation layer. The binary and synergistical post-treated films show enhanced crystallinity and improved molecular packing as well as better energy band alignment, benefiting for the hole extraction and transfer. Moreover, the surface defects are further passivated compared with unary passivation. Based on the strategy, a record-certified quasi-steady power conversion efficiency of 26.0% perovskite solar cells is achieved. The devices could maintain 81% of initial efficiency after 450 h maximum power point tracking.
The poor conductivity of passivators often impacts the charge carrier transport in perovskite solar cells. Here, the authors report a binary and synergistical post-treatment method to form the passivation layer, achieving certified quasi-steady power conversion efficiency of 26% for stable devices.
Journal Article
The paperboy
A paperboy and his dog enjoy the quiet of the early morning as they go about their rounds.
Book
Long-range hot-carrier transport in hybrid perovskites visualized by ultrafast microscopy
The Shockley-Queisser limit for solar cell efficiency can be overcome if hot carriers can be harvested before they thermalize. Recently, carrier cooling time up to 100 picoseconds was observed in hybrid perovskites, but it is unclear whether these long-lived hot carriers can migrate long distance for efficient collection. We report direct visualization of hot-carrier migration in methylammonium lead iodide (CH₃NH₃PbI₃) thin films by ultrafast transient absorption microscopy, demonstrating three distinct transport regimes. Quasiballistic transport was observed to correlate with excess kinetic energy, resulting in up to 230 nanometers transport distance that could overcome grain boundaries. The nonequilibrium transport persisted over tens of picoseconds and ~600 nanometers before reaching the diffusive transport limit. These results suggest potential applications of hot-carrier devices based on hybrid perovskites.
Journal Article