Biowaiver monographs for immediate release solid oral dosage forms: prednisolone.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongly suggest a BCS Class 1 classification. Prednisolone's therapeutic indications and therapeutic index, pharmacokinetics, and the possibility of excipient interactions were also taken into consideration. Available evidence indicates that a biowaiver for IR solid oral dosage forms formulated with the excipients tabulated in this article would be unlikely to expose patients to undue risks

Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol).

Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product

Biowaiver monographs for immediate release solid oral dosage forms: Aciclovir

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. However, in some countries also 800 mg tablets are available which fall just within BCS Class IV. Aciclovir seems not to be critical with respect to a risk for bio in equivalence, as no examples of bio in equivalence have been identified. It has a wide therapeutic index and is not used for critical indications. Hence, if: (a) the test product contains only excipients present in aciclovir solid oral IR drug products approved in ICH or associated countries, for instance as presented in this article; and (b) the comparator and the test product both are very rapidly dissolving , a biowaiver for IR aciclovir solid oral drug products is considered justified for all tablet strengths. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5061–5073, 2008Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61316/1/21392_ftp.pd

Biowaiver monographs for immediate release solid oral dosage forms: Doxycycline hyclate

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing doxycycline hyclate are reviewed. According to the Biopharmaceutics Classification System (BCS), doxycycline hyclate can be assigned to BCS Class I. No problems with BE of IR doxycycline formulations containing different excipients and produced by different manufacturing methods have been reported and hence the risk of bio in equivalence caused by these factors appears to be low. Doxycycline has a wide therapeutic index. Further, BCS-based dissolution methods have been shown to be capable of identifying formulations which may dissolve too slowly to generate therapeutic levels. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing doxycycline hyclate as the single Active Pharmaceutical Ingredient (API) provided that (a) the test product contains only excipients present in doxycycline hyclate IR solid oral drug products approved in the International Conference on Harmonization (ICH) or associated countries; and (b) the comparator and the test products comply with the BCS criteria for “very rapidly dissolving” or, alternatively, when similarity of the dissolution profiles can be demonstrated and the two products are “rapidly dissolving.”. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1639–1653, 2010Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64911/1/21954_ftp.pd

Modern Sedimentation and Authigenic Mineral Formation in the Chew Bahir Basin, Southern Ethiopia:Implications for Interpretation of Late Quaternary Paleoclimate Records

We present new mineralogical and geochemical data from modern sediments in the Chew Bahir basin and catchment, Ethiopia. Our goal is to better understand the role of modern sedimentary processes in chemical proxy formation in the Chew Bahir paleolake, a newly investigated paleoclimatic archive, to provide environmental context for human evolution and dispersal. Modern sediment outside the currently dry playa lake floor have higher SiO2 and Al2O3 (50-70 wt.%) content compared to mudflat samples. On average, mudflat sediment samples are enriched in elements such as Mg, Ca, Ce, Nd, and Na, indicating possible enrichment during chemical weathering (e.g., clay formation). Thermodynamic modeling of evaporating water in upstream Lake Chamo is shown to produce an authigenic mineral assemblage of calcite, analcime, and Mg-enriched authigenic illitic clay minerals, consistent with the prevalence of environments of enhanced evaporative concentration in the Chew Bahir basin. A comparison with samples from the sediment cores of Chew Bahir based on whole-rock MgO/Al2O3, Ba/Sr and authigenic clay mineral delta O-18 values shows the following: modern sediments deposited in the saline mudflats of the Chew Bahir dried out lake bed resemble paleosediments deposited during dry periods, such as during times of the Last Glacial Maximum and Younger Dryas stadial. Sediments from modern detrital upstream sources are more similar to sediments deposited during wetter periods, such as the early Holocene African Humid Period

Statement from the American Linear Collider Committee to the P5 subpanel

This statement from the American Linear Collider Committee to the P5 subpanel has three purposes. It presents a brief summary of the case for an $e^+e^-$ Higgs factory that has emerged from Snowmass 2021. It highlights the special virtues of the ILC that are shared with other linear colliders but not with circular colliders. Finally, it calls attention to the resources available in the ILC White Paper for Snowmass (arXiv:2203.07622). The ALCC urges P5 to move the Higgs factory forward as a global project by assigning the idea of an $e^+e^-$ Higgs factory high priority, initiating a global discussion of the technology choice and cost sharing, and offering the option of siting the Higgs factory in the U.S.Comment: 6 page

Resection of the mesopancreas (RMP): a new surgical classification of a known anatomical space

BACKGROUND: Prognosis after surgical therapy for pancreatic cancer is poor and has been attributed to early lymph node involvement as well as to a strong tendency of cancer cells to infiltrate into the retropancreatic tissue and to spread along the peripancreatic neural plexuses. The objective of our study was to classify the anatomical-surgical layer of the mesopancreas and to describe the surgical principles relevant for resection of the mesopancreas (RMP). Immunohistochemical investigation of the mesopancreatic-perineural lymphogenic structures was carried out with the purpose of identifying possible routes of metastatic spread. METHODS: Resection of the mesopancreas (RMP) was performed in fresh corpses. Pancreas and mesopancreas were separated from each other and the mesopancreas was immunohistochemically investigated. RESULTS: The mesopancreas strains itself dorsally of the mesenteric vessels as a whitish-firm, fatty tissue-like layer. Macroscopically, in the dissected en-bloc specimens of pancreas and mesopancreas nerve plexuses were found running from the dorsal site of the pancreatic head to the mesopancreas to establish a perineural plane. Immunohistochemical examinations revealed the lymphatic vessels localized in direct vicinity of the neuronal plexuses between pancreas and mesopancreas. CONCLUSION: The mesopancreas as a perineural lymphatic layer located dorsally to the pancreas and reaching beyond the mesenteric vessels has not been classified in the anatomical or surgical literature before. The aim to ensure the greatest possible distance from the retropancreatic lymphatic tissue which drains the carcinomatous focus can be achieved in patients with pancreatic cancer only by complete resection of the mesopancreas (RMP)

Depth-resolved measurement of the Meissner screening profile in a niobium thin film from spin-lattice relaxation of the implanted β\beta-emitter 8^{8}Li

We report measurements of the Meissner screening profile in a Nb(300 nm)/Al$_{2}$O$_{3}$ thin film using $^{8}$Li $\beta$-detected nuclear magnetic resonance ($\beta$-NMR). The NMR probe $^{8}$Li was ion-implanted into the Nb film at energies $\leq$ 20 keV, corresponding to mean stopping depths comparable to Nb's magnetic penetration depth $\lambda$. $^{8}$Li's strong dipole-dipole coupling with the host $^{93}$Nb nuclei provided a "cross-relaxation" channel that dominated in low magnetic fields, which conferred indirect sensitivity to the local magnetic field via the spin-lattice relaxation (SLR) rate $1/T_{1}$. From a fit of the $1/T_{1}$ data to a model accounting for its dependence on temperature, magnetic field, and $^{8}$Li$^{+}$ implantation energy, we obtained a magnetic penetration depth $\lambda_{0}$ = 51.5(22) nm, consistent with a relatively short carrier mean-free-path $\ell$ = 18.7(29) nm typical of similarly prepared Nb films. The results presented here constitute an important step towards using $^{8}$Li $\beta$-NMR to characterize bulk Nb samples with engineered surfaces, which are often used in the fabrication of particle accelerators.Comment: 16 pages, 4 figure

Pleistocene climate variability in eastern Africa influenced hominin evolution

AbstractDespite more than half a century of hominin fossil discoveries in eastern Africa, the regional environmental context of hominin evolution and dispersal is not well established due to the lack of continuous palaeoenvironmental records from one of the proven habitats of early human populations, particularly for the Pleistocene epoch. Here we present a 620,000-year environmental record from Chew Bahir, southern Ethiopia, which is proximal to key fossil sites. Our record documents the potential influence of different episodes of climatic variability on hominin biological and cultural transformation. The appearance of high anatomical diversity in hominin groups coincides with long-lasting and relatively stable humid conditions from ~620,000 to 275,000 years bp (episodes 1–6), interrupted by several abrupt and extreme hydroclimate perturbations. A pattern of pronounced climatic cyclicity transformed habitats during episodes 7–9 (~275,000–60,000 years bp), a crucial phase encompassing the gradual transition from Acheulean to Middle Stone Age technologies, the emergence of Homo sapiens in eastern Africa and key human social and cultural innovations. Those accumulative innovations plus the alignment of humid pulses between northeastern Africa and the eastern Mediterranean during high-frequency climate oscillations of episodes 10–12 (~60,000–10,000 years bp) could have facilitated the global dispersal of H. sapiens.</jats:p