Since 1998 the serious public health problem in South East Asia of counterfeit artesunate, containing no or subtherapeutic amounts of the active antimalarial ingredient, has led to deaths from ...untreated malaria, reduced confidence in this vital drug, large economic losses for the legitimate manufacturers, and concerns that artemisinin resistance might be engendered.
With evidence of a deteriorating situation, a group of police, criminal analysts, chemists, palynologists, and health workers collaborated to determine the source of these counterfeits under the auspices of the International Criminal Police Organization (INTERPOL) and the Western Pacific World Health Organization Regional Office. A total of 391 samples of genuine and counterfeit artesunate collected in Vietnam (75), Cambodia (48), Lao PDR (115), Myanmar (Burma) (137) and the Thai/Myanmar border (16), were available for analysis. Sixteen different fake hologram types were identified. High-performance liquid chromatography and/or mass spectrometry confirmed that all specimens thought to be counterfeit (195/391, 49.9%) on the basis of packaging contained no or small quantities of artesunate (up to 12 mg per tablet as opposed to approximately 50 mg per genuine tablet). Chemical analysis demonstrated a wide diversity of wrong active ingredients, including banned pharmaceuticals, such as metamizole, and safrole, a carcinogen, and raw material for manufacture of methylenedioxymethamphetamine ('ecstasy'). Evidence from chemical, mineralogical, biological, and packaging analysis suggested that at least some of the counterfeits were manufactured in southeast People's Republic of China. This evidence prompted the Chinese Government to act quickly against the criminal traders with arrests and seizures.
An international multi-disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation. International cross-disciplinary collaborations may be appropriate in the investigation of other serious counterfeit medicine public health problems elsewhere, but strengthening of international collaborations and forensic and drug regulatory authority capacity will be required.
Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy ...(ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa.
Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed.
Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa.
Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.
Neutron stars are not only of astrophysical interest, but are also of great interest to nuclear physicists because their attributes can be used to determine the properties of the dense matter in ...their cores. One of the most informative approaches for determining the equation of state (EoS) of this dense matter is to measure both a star's equatorial circumferential radius Re and its gravitational mass M. Here we report estimates of the mass and radius of the isolated 205.53 Hz millisecond pulsar PSR J0030+0451 obtained using a Bayesian inference approach to analyze its energy-dependent thermal X-ray waveform, which was observed using the Neutron Star Interior Composition Explorer (NICER). This approach is thought to be less subject to systematic errors than other approaches for estimating neutron star radii. We explored a variety of emission patterns on the stellar surface. Our best-fit model has three oval, uniform-temperature emitting spots and provides an excellent description of the pulse waveform observed using NICER. The radius and mass estimates given by this model are km and (68%). The independent analysis reported in the companion paper by Riley et al. explores different emitting spot models, but finds spot shapes and locations and estimates of Re and M that are consistent with those found in this work. We show that our measurements of Re and M for PSR J0030+0451 improve the astrophysical constraints on the EoS of cold, catalyzed matter above nuclear saturation density.
Transplantation of human embryonic stem cells (hESC) into immune-deficient mice leads to the formation of differentiated tumors comprising all three germ layers, resembling spontaneous human ...teratomas. Teratoma assays are considered the gold standard for demonstrating differentiation potential of pluripotent hESC and hold promise as a standard for assessing safety among hESC-derived cell populations intended for therapeutic applications. We tested the potency of teratoma formation in seven anatomical transplantation locations (kidney capsule, muscle, subcutaneous space, peritoneal cavity, testis, liver, epididymal fat pad) in SCID mice with and without addition of Matrigel, and found that intramuscular teratoma formation was the most experimentally convenient, reproducible, and quantifiable. In the same experimental setting, we compared undifferentiated hESC and differentiated populations enriched for either beating cardiomyocytes or definitive endoderm derivatives (insulin-secreting beta cells), and showed that all cell preparations rapidly formed teratomas with varying percentages of mesoderm, ectoderm, and endoderm. In limiting dilution experiments, we found that as little as two hESC colonies spiked into feeder fibroblasts produced a teratoma, while a more rigorous single-cell titration achieved a detection limit of 1/4000. In summary, we established core parameters essential for facilitating safety profiling of hESC-derived products for future therapeutic applications.
Riparian municipal wells, that are located on riverbanks, are specifically designed to capture a portion of the river water through induced infiltration. Runoff from agricultural watersheds is found ...to carry enormous amounts of pesticides and nitrate. While the risk of contamination for a vast majority of sites with small-capacity vertical wells is low, potential exists for medium to large capacity collector wells to capture a fraction of the surface water contaminants during flood. Prior monitoring and current modeling results indicate that a small-capacity (peak pumpage 0.0315
m
3/s) vertical bank filtration well may not be affected by river water nitrate and atrazine even during flood periods. For a medium capacity (0.0875–0.175
m
3/s) hypothetical collector well at the same site, potential exists for a portion of the river water nitrate and atrazine to enter the well during flood periods. Various combinations of hydraulic conductivity of the riverbed or bank material were used. For nitrate, it was assumed either no denitrification occurred during the period of simulation or a half-life of 2 years. Equilibrium controlled sorption (organic carbon partition coefficient of 52
ml/g) and a half-life of between 7.5 and 15 weeks were considered for atrazine. Combinations of these parameters were used in various simulations. Peak concentrations of atrazine or nitrate in pumped water could vary from less than 1% to as high as 90% of that in the river. It was found that a combination of river stage, pumping rates, hydraulic properties of the riverbed and bank, and soil/pesticide properties could affect contaminant entry from river water to any of these wells. If the hydraulic conductivity of the bed and bank material were low, atrazine would not reach the pumping well with or without sorption and degradation. However, for moderately low permeable bank and bed materials, some atrazine from river water could enter a hypothetical collector well while pumping at 0.0875
m
3/s. It was interesting to note that doubling the pumpage of this collector well would bring in more ground water from the aquifer (with no atrazine) and thus have a lower concentration of atrazine in the filtrate. For highly conductive banks, it is possible to find some atrazine at a vertical well for a sustained pumpage rate of 0.0125
m
3/s if the effect of sorption is neglected. However, with equilibrium sorption, the concentration would be below the detection limit. On the other hand, if a collector well of capacity 0.0875
m
3/s is used at the place of the vertical well with highly conductive banks, atrazine concentration in the filtrate would be about 80% of river water even assuming equilibrium sorption and a half-life of 7.5 weeks. Remediation of river water contamination of the aquifer using ‘scavenger’ wells between the river and the pumping well(s) was not a feasible option due to the contact of the aquifer with a highly conductive bank at the site. However, moving the existing pumping well(s) 100
m upstream would have negligible impact from the bank-stored water.
A 175-mi (282-km) stretch of the Illinois River was studied to assess the potential effects of flooding on the quality of pumped groundwater. Water pumped from four municipal water supply wells ...(pumping rates, 140-500 gpm 0.009-0.03 m³/s) was analyzed. Three of these wells were vertical wells located 175-220 ft (53-67 m) from the river's edge at normal pool stages. The fourth well was a radial-arm collector well with laterals extending beneath the river bed. Although concentrations of atrazine in the Illinois River during peak flows of 1995 and 1996 were as high as 6 and 12 μg/L, respectively, the concentration of atrazine in groundwater pumped at the three vertical-well sites remained below the 0.1-μg/L detection limit. In 1996 a small breakthrough of atrazine was observed in the collector well water. The high concentration of nitrate in river water appeared to have slightly increased the nitrate in pumped groundwater at two locations. Dilution and other factors may have affected the transport of river water contaminants in the alluvial aquifer between the river and the pumping wells.
Neutron stars are not only of astrophysical interest, but are also of great interest to nuclear physicists, because their attributes can be used to determine the properties of the dense matter in ...their cores. One of the most informative approaches for determining the equation of state of this dense matter is to measure both a star's equatorial circumferential radius \(R_e\) and its gravitational mass \(M\). Here we report estimates of the mass and radius of the isolated 205.53 Hz millisecond pulsar PSR J0030+0451 obtained using a Bayesian inference approach to analyze its energy-dependent thermal X-ray waveform, which was observed using the Neutron Star Interior Composition Explorer (NICER). This approach is thought to be less subject to systematic errors than other approaches for estimating neutron star radii. We explored a variety of emission patterns on the stellar surface. Our best-fit model has three oval, uniform-temperature emitting spots and provides an excellent description of the pulse waveform observed using NICER. The radius and mass estimates given by this model are \(R_e = 13.02^{+1.24}_{-1.06}\) km and \(M = 1.44^{+0.15}_{-0.14}\ M_\odot\) (68%). The independent analysis reported in the companion paper by Riley et al. (2019) explores different emitting spot models, but finds spot shapes and locations and estimates of \(R_e\) and \(M\) that are consistent with those found in this work. We show that our measurements of \(R_e\) and \(M\) for PSR J0030\(+\)0451 improve the astrophysical constraints on the equation of state of cold, catalyzed matter above nuclear saturation density.
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