Precision results on cosmic-ray electrons are presented in the energy range from 0.5 GeV to 1.4 TeV based on 28.1×10^{6} electrons collected by the Alpha Magnetic Spectrometer on the International ...Space Station. In the entire energy range the electron and positron spectra have distinctly different magnitudes and energy dependences. The electron flux exhibits a significant excess starting from 42.1_{-5.2}^{+5.4} GeV compared to the lower energy trends, but the nature of this excess is different from the positron flux excess above 25.2±1.8 GeV. Contrary to the positron flux, which has an exponential energy cutoff of 810_{-180}^{+310} GeV, at the 5σ level the electron flux does not have an energy cutoff below 1.9 TeV. In the entire energy range the electron flux is well described by the sum of two power law components. The different behavior of the cosmic-ray electrons and positrons measured by the Alpha Magnetic Spectrometer is clear evidence that most high energy electrons originate from different sources than high energy positrons.
In order to understand the membrane wetting in microporous hollow fiber membrane contactors, a theoretical model was developed by simulating CO2 absorption in water under two extreme operating ...conditions of the non-wetted and wetted modes. The experimental studies on CO2 absorption using an aqueous DEA solution as the absorbent in a polypropylene hollow fiber membrane contactor were also conducted over a three-month period of time. Simulation results show that the CO2 absorption rate in the non-wetted mode is six times higher than those of the wetted mode of operation. The deteriorated performance in the wetted mode is mainly attributed to the mass transfer resistance imposed by the liquid in the membrane pores.
Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of ...global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs.
Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis.
One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001).
Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs.
•Before undertaking this study, we searched academic databases for all English systematic reviews on global orphan drug policies published before July 2019. We identified 1 review on orphan drug policies published in 2015 and 2 reviews on laws and national strategies for rare diseases from selected countries that were published in 2017 and 2018, respectively. These 3 reviews uncovered a plethora of governmental efforts that facilitate the availability of and access to orphan drugs, with critical differences in scope and approaches among countries.•Vast areas worldwide were omitted from previous reviews, such as Africa, India, Latin America, and Russia. No studies attempted an overview of orphan drug policies in all countries with both governmental and academic evidence. The current global landscape of orphan drug policy (ODP) remains unclear. By systematically reviewing pharmaceutical policies and academic literature from 200 countries/areas, our study presents the most comprehensive review on global ODP to date.•Of the 200 countries or areas examined, 92 had ODPs alongside a notable increase in ODP establishment in non-high-income countries/areas over the last decade. Our findings highlight disparities in ODP establishment and scope in countries/areas with different income levels. This allows respective stakeholders to reference orphan drug regulatory standards of countries/areas with similar political realities while informing policy formulation and advocacy direction for treatment access of patients with rare diseases.
The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next ...generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.
Abstract Based on e + e − collision data collected at center-of-mass energies from 2.000 to 3.080 GeV by the BESIII detector at the BEPCII collider, a partial wave analysis is performed for the ...process e + e − → K S 0 K L 0 $$ {K}_S^0{K}_L^0 $$ π 0. The results allow the Born cross sections of the process e + e − → K S 0 K L 0 $$ {K}_S^0{K}_L^0 $$ π 0, as well as its subprocesses e + e − → K ∗(892)0 K ¯ $$ \overline{K} $$ 0 and K 2 ∗ $$ {K}_2^{\ast } $$ (1430)0 K ¯ $$ \overline{K} $$ 0 to be measured. The Born cross sections for e + e − → K S 0 K L 0 $$ {K}_S^0{K}_L^0 $$ π 0 are consistent with previous measurements by BaBar, but with substantially improved precision. The Born cross section lineshape of the process e + e − K ∗(892)0 K ¯ $$ \overline{K} $$ 0 is consistent with a vector meson state around 2.2 GeV with a significance of 3.2σ. A Breit-Wigner fit determines its mass as M Y = (2164.7 ± 9.1 ± 3.1) MeV/c 2 and its width as Γ Y = (32.4 ± 21.0 ± 1.8) MeV.
Observation of the Dalitz decay η ′ → γ e + e Achasov, M. N.; Amoroso, A.; An, F. F. ...
Physical review. D, Particles, fields, gravitation, and cosmology,
7/2015, Volume:
92, Issue:
1
Journal Article
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