Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of Ceftaroline Fosamil in a Staphylococcal Murine Pneumonia Model

ABSTRACT Ceftaroline fosamil is a cephalosporin with activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to characterize the dose-response relationship of ceftaroline fosamil against S. aureus in an immunocompromised murine pneumonia model, as well as to evaluate the efficacy of the humanized regimen of 600 mg intravenously (i.v.) every 12 h. Seventeen S. aureus (2 methicillin-susceptible Staphylococcus aureus [MSSA], 15 MRSA) isolates with ceftaroline MICs of 0.5 to 4 μg/ml were utilized. The pharmacokinetics of ceftaroline in serum and epithelial lining fluid (ELF) were evaluated to determine bronchopulmonary exposure profiles in infected and uninfected animals, using single and human-simulated doses. Serum fT>MIC (the percentage of time that free drug concentrations remain above the MIC) of 17% to 43% was required to produce a 1-log10 kill in the dose-ranging studies. These targets were readily achieved with the humanized exposure profile, where decreases of 0.64 to 1.95 log10 CFU were observed against 13 MRSA and both MSSA isolates tested. When taken as a composite, the fT>MICs required for stasis and a 1-log10 kill were 16% and 41%, respectively. ELF concentrations were similar to serum concentrations across the dosing interval in infected and uninfected animals. The serum fT>MIC targets required in this lung infection model were similar to those observed with ceftaroline against S. aureus in a murine thigh infection model. Exposures simulating the human dose of 600 mg i.v. every 12 h achieved pharmacodynamic targets against MRSA and MSSA considered susceptible by current U.S. FDA breakpoints.
The 117 call alert system in Sierra Leone: from rapid Ebola notification to routine death reporting

A toll-free, nationwide phone alert system was established for rapid notification and response during the 2014–2015 Ebola epidemic in Sierra Leone. The system remained in place after the end of the epidemic under a policy of mandatory reporting and Ebola testing for all deaths, and, from June 2016, testing only in case of suspected Ebola. We describe the design, implementation and changes in the system; analyse calling trends during and after the Ebola epidemic; and discuss strengths and limitations of the system and its potential role in efforts to improve death reporting in Sierra Leone. Numbers of calls to report deaths of any cause (death alerts) and persons suspected of having Ebola (live alerts) were analysed by province and district and compared with numbers of Ebola cases reported by the WHO. Nearly 350 000 complete, non-prank calls were made to 117 between September 2014 and December 2016. The maximum number of daily death and live alerts was 9344 (October 2014) and 3031 (December 2014), respectively. Call volumes decreased as Ebola incidence declined and continued to decrease in the post-Ebola period. A national social mobilisation strategy was especially targeted to influential religious leaders, traditional healers and women’s groups. The existing infrastructure and experience with the system offer an opportunity to consider long-term use as a death reporting tool for civil registration and mortality surveillance, including rapid detection and control of public health threats. A routine social mobilisation component should be considered to increase usage.
Food markets’ structural empirical analysis: a review of methods and topics

We review the current literature on applied policy analysis and empirical structural food industrial organisation research. Within that context, we provide an overview on the state of research and summarise the core problems researchers face when estimat- ing the demand and structural supply models implemented in applied research to date. We focus on important themes, such as providing a better understanding of ver- tical relationships in food markets, price formation, competition issues, environmen- tal and nutritional policies.
Pregnancy-specific protein B and progesterone concentrations in French Alpine goats throughout gestation.

The 34 French Alpine dairy goats originated from a single flock and were artificially inseminated 44 h after synchronization of oestrus. They were bled daily at the jugular vein from 15 to 27 days after AI. An early pregnancy diagnosis by RIA of progesterone concentration was performed 21 days after AI. In pregnant goats (greater than 1.5 ng progesterone/ml) daily sampling was extended until 30 days after AI and, from those, 9 were bled every 2 weeks until the end of pregnancy and at 50 and 63 days post partum. Pregnancy-specific protein B (PSPB) was also assayed. The kidding rate was 67.6% (23/34). PSPB concentrations (ng/ml) in pregnant goats were significantly different from those of non-pregnant goats at 24 days after AI (0.82 +/- 0.18 vs 1.78 +/- 0.19; mean +/- s.e.m.) and rose to 40 ng/ml at the end of pregnancy. From Day 25 and throughout gestation, females with 2 fetuses had higher PSPB concentrations than did those with a single fetus (P less than 0.05). In the 2 goats exhibiting late embryonic mortality according to progesterone concentrations, one had a PSPB profile very similar to those of pregnant goats until 30 days while the other did not show any elevation of PSPB concentration. It is concluded that PSPB profiles in goats are similar to those found in cows throughout pregnancy and that PSPB RIA may be useful for pregnancy diagnosis or diagnosis of late embryonic mortality.
Economic History and Contemporary Challenges to Globalization

The article surveys three economic history literatures that can speak to contemporary challenges to globalization: the literature on the anti-globalization backlash of the nineteenth century, focused largely on trade and migration; the literature on the Great Depression, focused largely on capital flows, the gold standard, and protectionism; and the literature on trade and warfare.
A novel and efficient tool for locating and characterizing protein cavities and binding sites

Systematic investigation of a protein and its binding site characteristics are crucial for designing small molecules that modulate protein functions. However, fundamental uncertainties in binding site interactions and insufficient knowledge of the properties of even well‐defined binding pockets can make it difficult to design optimal drugs. Herein, we report the development and implementation of a cavity detection algorithm built with HINT toolkit functions that we are naming Vectorial Identification of Cavity Extents (VICE). This very efficient algorithm is based on geometric criteria applied to simple integer grid maps. In testing, we carried out a systematic investigation on a very diverse data set of proteins and protein–protein/protein–polynucleotide complexes for locating and characterizing the indentations, cavities, pockets, grooves, channels, and surface regions. Additionally, we evaluated a curated data set of unbound proteins for which a ligand‐bound protein structures are also known; here the VICE algorithm located the actual ligand in the largest cavity in 83% of the cases and in one of the three largest in 90% of the cases. An interactive front‐end provides a quick and simple procedure for locating, displaying and manipulating cavities in these structures. Information describing the cavity, including its volume and surface area metrics, and lists of atoms, residues, and/or chains lining the binding pocket, can be easily obtained and analyzed. For example, the relative cross‐sectional surface area (to total surface area) of cavity openings in well‐enclosed cavities is 0.06 ± 0.04 and in surface clefts or crevices is 0.25 ± 0.09. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Does reading in shallow L1 orthography slow attrition of language-specific morphological structures?

This study looks at the relationship between L1 (Russian) attrition and L1 reading ability in Russian–English-speaking bilingual children. Ten Russian–English bilingual children and 10 adults participated in this study. Nine out of 10 children participants were born in the US and used L1 as their primary language of interaction within the family, but the intensity and the length of uninterrupted L1 exposure differed for each child. All participants were tested on perception (grammaticality judgement) and production (narrative) tasks to assess their sensitivity to and retention of the morphosyntactic structure of L1. All children showed some attrition of grammatical morphemes, specifically in the Russian systems of declension and conjugation; however, the degree of attrition correlated with reading ability in L1, i.e. children with L1 reading skills showed a lesser degree of attrition for some language-specific morphosyntactic structures. This finding shows interdependence of oral and reading skills and points to the role reading in language with shallow orthography may play in preservation of L1 grammatical structures in oral language. The implications for the clinical applications are also discussed.
Test-Retest Nasalance Score Variability in Hypernasal Speakers

Objective The objective of this study was to evaluate test-retest nasalance score variability in subjects with hypernasal resonance. Design Two groups of subjects with hypernasal speech recited both the Turtle Passage and the Mouse Passage two times each. For one group, the Nasometer headgear was not changed between repetitions of each stimulus (NCHG; n = 17); and for the other group, the headgear was changed between repetitions (CHG; n = 18). Three subjects in the CHG group would not recite the Mouse Passage two times. Participants The subjects were 35 patients with hypernasal speech followed by a cleft palate team. Main Outcome Measures The outcome measures were the four nasalance scores obtained for each subject. Results There was no significant difference between first and second repetitions for either stimulus in either the NCHG group or in the CHG group. Cumulative frequency tables showed that for the Turtle Passage-NCHG condition, 15 of the 17 (88%) repeated nasalance scores were within 5 nasalance points of each other. For the CHG condition, however, only 9 of 18 (50%) repeated nasalance scores were within 5 points. For the Mouse Passage-NCHG condition, 15 of the 17 (88%) repeated nasalance scores were within 5 points. For the CHG condition, however, only 11 of 15 (73%) repeated scores were within 5 points. Conclusions Test-retest variability was greater in a population of hypernasal patients than that reported in other studies for normal speakers, and headgear change increased test-retest variability.
The Northern Ireland Audit Office Report on Homelessness: A Missed Opportunity

Abstract_This article reviews the Northern Ireland (NI) Audit Office report on Homelessness in Northern Ireland (2017), placing it in the context of the existing body of knowledge regarding the efficacy of legislative, policy and strategic approaches to homelessness. A key emphasis is on the extent to which the report might support and direct meaningful change in respect to preventing and mitigating homelessness in NI, given that this issue has attracted enduring and intense policy attention, but with more limited substantive progress than might have been hoped for. The report’s highly critical focus on deficits in data collection, evaluation and monitoring processes represents a welcome contribution to longstanding demands for improved performance in these respects, albeit that the Audit Office’s own analysis appears to be framed by a flawed understanding of homelessness causation. On the critical topic of increasing housing supply and reducing housing demand, the report’s failure to make recommendations that might support the type of radical change in responses to homelessness evident elsewhere in the UK (namely, housingled, rapid-rehousing and Housing First approaches), is likely to come as a disappointment to many.
Application of ELISA-based kit for detecting AOZ and determining its clearance in eel tissues

Furazolidone, an antibacterial drug that was once widely used in the livestock industry and aquaculture, is now prohibited in numerous countries. It is difficult to detect residual furazolidone because it is readily metabolized in animal tissues but, by using and liquid chromatography coupled with tandem mass spectrometry, its metabolite, 3-amino-2-oxazolidinone (AOZ) can be detected. Here we describe the validity of an enzyme-linked immunosorbent assay (ELISA) kit to detect AOZ in Japanese eel Anguilla japonica tissue. ELISA is capable of detecting AOZ at 1.0 μg/kg in an eel sample with excellent accuracy and precision. Our results show that ELISA is suitable for regulatory purposes and for studying the fate of AOZ residues in eel treated with furazolidone. To measure the persistence of AOZ in eel tissues, eels (1.4–6.5g) were immersed in tanks containing 2 and 10 mg furazolidone/L for 3 h, and then maintained in a tank supplying well water for the next 160 days. The half-lives of AOZ, calculated from the linear terminal part of the excretion curve, were 25.0 days in muscle and 21.6 days in liver from fish exposed to 2 mg/L furazolidone. In the eels treated with 10 mg/L furazolidone, by contrast, high levels of AOZ were detected in liver and muscle, but the half-lives of AOZ were similar to those in fish treated with 2 mg/L furazolidone. The half-lives of AOZ in eel tissues were prolonged by the condition of low water temperature.
A Transit Compartment Model Unmasks OxyContin's Reflective Pharmacokinetics From Urine Measurements in Humans

ABSTRACT The absorption pattern of orally administered OxyContin (OXC) reflected in urine indicates that its appearance into systemic circulation undergoes transit absorption delays. The authors developed an OXC transit-delay compartment model that identified a new source of oxycodone hydrochloride (OC): the rate of appearance of OC due to OXC tablet dissolution in transit through the gastrointestinal (GI) tract (RGIa), which is due to disintegration of OXC's AcroContin delivery system. RGIa is independent of the biphasic dissolution and release of OC from the delivery system. The authors conclude that an OXC transit-delay compartment model can be of value in the interpretation of OXC pharmacokinetics.
The Chandra X-Ray Observatory: progress report and highlights

Over the past 13 years, the Chandra X-ray Observatory’s ability to provide high resolution X-ray images and spectra have established it as one of the most versatile and powerful tools for astrophysical research in the 21st century. Chandra explores the hot, x-ray-emitting regions of the universe, observing sources with fluxes spanning more than 10 orders of magnitude, from the X-ray brightest, Sco X-1, to the faintest sources in the Chandra Deep Field South survey. Thanks to its continuing operational life, the Chandra mission now also provides a long observing baseline which, in and of itself, is opening new research opportunities. In addition, observations in the past few years have deepened our understanding of the co-evolution of supermassive black holes and galaxies, the details of black hole accretion, the nature of dark energy and dark matter, the details of supernovae and their progenitors, the interiors of neutron stars, the evolution of massive stars, and the high-energy environment of protoplanetary nebulae and even the interaction of an exo-planet with its star. Here we update the technical status, highlight some of the scientific results, and very briefly discuss future prospects. We fully expect that the Observatory will continue to provide outstanding scientific results for many years to come.
Measurement of Social Networks for Innovation within Community Disaster Resilience

Disaster risk reduction (DRR) research has long recognised that social networks are a vital source of support during and after a shock. However, the quantification of this social support, primarily through its recognition as social capital, has proven problematic as there is no singular method for its measurement, invalidating the credibility of studies that try to correlate its effects with community disaster resilience. Within the wider resilience field, research that specifically utilises social networks as the focus of analysis is evolving. This paper provides a critical synthesis of how this developing discourse is filtering into community disaster resilience, reviewing empirical case studies from the Global South within DRR that use social network analysis and connectivity measurement. Our analysis of these studies indicates that a robust methodology utilising social network analysis is emerging, which offers opportunity for research cross-comparability. Our review also finds that without this bottom-up mapping, the implementation of top-down preparedness policy and procedures are likely to fail, resulting in the advocation of social network analysis as a critical methodology in future resilience research and policy planning.
WNK3, a kinase related to genes mutated in hereditary hypertension with hyperkalaemia, regulates the K+ channel ROMK1 (Kir1.1)

The serine–threonine kinase WNK3 modulates Cl− transport into and out of cells through its regulation of SLC12A cation–Cl− cotransporters, implicating it as (one of) the long‐sought Cl−/volume‐sensitive kinase(s). Integrators in homeostatic systems regulate structurally diverse but functionally coupled elements. For example, the related kinase WNK4 regulates the Na+–Cl− cotransporter (NCC), paracellular Cl− flux, and the K+ channel ROMK1 (Kir1.1) to maintain renal NaCl and K+ homeostasis; mutations in PRKWNK4, encoding WNK4, cause a Mendelian disease featuring hypertension and hyperkalaemia. It is known that WNK3 is expressed in the nephron's distal convoluted tubule (DCT) and stimulates NCC activity. Here, we show that WNK3 is also expressed in cortical and outer medullary collecting duct principal cells. Accordingly, we tested WNK3's effect on the mediators of NaCl and K+ handling in these nephron segments – the epithelial sodium channel (ENaC), paracellular Cl− flux, and ROMK1 – using established model systems. WNK3 did not alter paracellular Cl− flux in tetracycline‐responsive MDCK II cells, nor affect amiloride‐sensitive currents when coexpressed with ENaC in Xenopus laevis oocytes. However, additional coexpression studies in oocytes revealed WNK3 inhibited the renal‐specific K+ channel ROMK1 activity greater than 5.5‐fold (P < 0.0001) by altering its plasmalemmal surface expression; WNK3 did not affect ROMK1's conductance or open/closed probability. In contrast, WNK3 had no effect on the activity of the cardiac long‐QT syndrome K+ channel KCNQ1/KCNE1 when coexpressed in oocytes. Inhibition of ROMK1 is independent of WNK3's catalytic activity and is mediated by WNK3's carboxyl terminus – a mechanism distinct from its known kinase‐dependent activation of NCC. A kinase‐inactivating point mutation or a missense mutation homologous to one in WNK4 that causes disease produced a gain‐of‐function effect, enhancing WNK3's inhibition of ROMK1 greater than 2.5‐fold relative to wild‐type kinase (P < 0.0001). The magnitude and specificity of WNK3's effects at both NCC and ROMK1, its coexpression with its targets in the distal nephron, and the established in vivo effect of WNK4 at these same targets provide evidence that WNK3's action is physiologically relevant. WNK3 is probably a component of one of the mechanisms that determines the balance between renal NaCl reabsorption and K+ secretion.
Family Interactions Among African American Prostate Cancer Survivors

Prostate cancer affects African Americans at a higher rate than any other ethnic group in the United States. Prostate cancer does not only affect the man with the disease but also affects those individuals who are closest to him, such as his family and friends. Open communication is valuable in coping with stressors that are affiliated with chronic illnesses. This article focuses on family and friend social support of men with prostate cancer. Data analysis revealed that support from family members and friends plays an important role in how men cope with their treatment and recovery from prostate cancer.
Spontaneous Skin Neoplasms in Long-Evans Rats

Two hundred sixty-one neoplasms involving the skin and its appendages were observed in a total of 980 (490 of each sex) Long-Evans (LE) control rats of 7 carcinogenicity studies. All studies were 2 yr in duration and were conducted in the years 1983 through 1994. Skin neoplasms were reevaluated and classified according to current criteria and nomenclature. The various neoplasm incidences were compared to those published for Sprague-Dawley (SD), Fischer-344 (F-344), and Wistar rats. The most common neoplasms involved the mammary glands, affecting 28% of LE females. This incidence is comparable to the 31% incidence reported for SD females. Mammary gland fibroadenomas were observed in 22% of LE females compared to 19-31% of SD, 7-29% of F-344, and 4-25% of Wistar females. Mammary gland adenocarcinomas occurred in 7% of LE females in our laboratory, while incidences of 9-17% of SD, 0-2% of F-344, and 1-13% of Wistar females are reported. In LE males, the incidences of mammary gland fibroadenomas (1%) and adenocarcinomas (0.6%) were comparable to the 0-3% reported recently in other strains. As is observed in other strains, the incidence of nonmammary gland skin neoplasms in LE males (11.4%) was greater than the incidence in females (2.7%). Fibromas were the most common nonmammary gland skin neoplasm and affected 3.3% of males and 0.6% of females. The incidences of fibromas in SD, F-344, and Wistar rats range from 0-7%, 0-3.2%, and 0-12%, respectively, in males and from 0-3.3%, 0-1.1%, and 0-4%, respectively, in females. Of the 4 strains, only SD males have more nonmammary gland epithelial than mesenchymal skin neoplasms. The difference between the LE and SD males can be attributed to the criteria used to classify keratoacanthomas. Only one keratoacanthoma was observed in LE rats in this review. Reevaluation of skin neoplasms found in 980 LE control rats and comparison of the resulting incidences with those of other strains demonstrated that most skin neoplasms in LE rats have comparable incidences to those reported for SD, F-344, and Wistar rats.