bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination of dihydromyricetin and ondansetron strengthens antiproliferative efficiency of adriamycin in K562/ADR through downregulation of SORCIN: A new strategy of inhibiting P‐glycoprotein
Authors: Sun Yaoting , Liu Wei , Wang Changyuan , Meng Qiang , Liu Zhihao , Huo Xiaokui , Yang Xiaobo , Sun Pengyuan , Sun Huijun , Ma Xiaodong , Peng Jinyong , Liu Kexin
Published: September 2018

Though the advancement of chemotherapy drugs alleviates the progress of cancer, long‐term therapy with anticancer agents gradually leads to acquired multidrug resistance (MDR), which limits the survival outcomes in patients. It was shown that dihydromyricetin (DMY) could partly reverse MDR by suppressing P‐glycoprotein (P‐gp) and soluble resistance‐related calcium‐binding protein (SORCIN) independently. To reverse MDR more effectively, a new strategy was raised, that is, circumventing MDR by the coadministration of DMY and ondansetron (OND), a common antiemetic drug, during cancer chemotherapy. Meanwhile, the interior relation between P‐gp and SORCIN was also revealed. The combination of DMY and OND strongly enhanced antiproliferative efficiency of adriamycin (ADR) because of the increasing accumulation of ADR in K562/ADR‐resistant cell line. DMY could downregulate the expression of SORCIN and P‐gp via the ERK/Akt pathways, whereas OND could not. In addition, it was proved that SORCIN suppressed ERK and Akt to inhibit P‐gp by the silence of SORCIN, however, not vice versa. Finally, the combination of DMY, OND, and ADR led to G2/M cell cycle arrest and apoptosis via resuming P53 function and restraining relevant proteins expression. These fundamental findings provided a promising approach for further treatment of MDR.
Synthesis and biodistribution studies of 99mTc labeled fatty acid derivatives prepared via “Click approach” for potential use in cardiac imaging
Authors: Das Soumen , Mathur Anupam , Sakhare Navin , Mallia Madhava B. , Sarma Haladhar Dev , Sachdev Satbir Singh , Dash Ashutosh
Published: September 2018

123I‐Iodophenylpentadecanoic acid (IPPA) is a metabolic agent used in nuclear medicine for diagnosis of myocardial defects. Efforts are underway worldwide to develop a 99mTc substitute of the above radiopharmaceutical for the aforementioned application. Herein, we report synthesis and biodistribution studies of 99mTc labeled fatty acids (8, 11, and 15 carbons) obtained via “click chemistry” for its potential use in myocardial imaging.

ω‐Bromo fatty acids (8C/11C/15C) were synthetically modified at bromo terminal to introduce a heterocyclic triazole with glycine sidearm in a five step procedure. Modified fatty acids were subsequently radiolabeled with preformed [99mTc(CO)3]+ synthon to yield the desired fatty acid complexes which were evaluated in Swiss mice.

All the radiolabeled complexes were obtained with radiochemical purities >80%, as characterized by HPLC. Biodistribution studies of all three complexes in Swiss mice showed myocardial uptake of ~6‐9% ID/g at 2 minutes post‐injection, close to*I‐IPPA (~9% ID/g). Complexes exhibited significant retention in the myocardium up to 30 minutes (~1% ID/g) but were lower to the standard agent (~7% ID/g).

Similar uptake of activity in myocardium for the newly synthesized complexes in comparison to 125I‐IPPA along with favorable in vivo pharmacokinetics merits potential for the present “click” design of complexes for myocardial imaging.
Eine Prise Kohlenstoff für die Erde
Authors: Gail Hans‐Peter , Trieloff Mario
Published: September 2018

Obwohl Kohlenstoff nach kosmischen Maßstäben häufig ist, hat unser Heimatplanet nur eine verschwindend kleine Menge davon mitbekommen. Dafür scheinen Hochtemperaturprozesse verantwortlich zu sein, die bei der Planetenentstehung im frühen Sonnensystem auftraten. Solche Prozesse sind von
Polykristalline Oberflächen als Strukturbibliothek
Authors: Suchorski Yuri , Rupprechter Günther
Published: September 2018

Um heterogene Katalyse zu verstehen, sind Oberflächenstrukturbibliotheken oft besser geeignet als Einkristalle: Kombiniert mit ortsaufgelösten kinetischen Experimenten lassen sich damit die Eigenschaften verschiedener kristallographischer Orientierungen unter identischen Reaktionsbedingungen gleichzeitig bestimmen. Die Oberflächen polykristalliner Edelmetallfolien und gekrümmter Kristalle geben Einblicke in katalytische Zündung, Reaktionsfrontfortpflanzung und oszillierende Oberflächenreaktionen.
Von Kautschuk zu Metallen: ein Werkslabor mit Weltgeltung
Authors: Möckl Leonhard , Evers Jürgen , Herzog Christiane
Published: September 2018

Anfang des 20. Jahrhunderts leitete zunächst der Chemiker Salomon Axelrod das chemische Laboratorium im Kabelwerk Oberspree. Sein Hauptforschungsgebiet war Kautschuk. Nach seinem Tod übernahm der Ingenieur Wichard von Moellendorff die Leitung des Labors, und Forschungsschwerpunkt wurden Metalle. Der Name eines seiner Laboranten steht noch heute in Chemiebüchern: Jan Czochralski.
Labortechnik ‐ Digital statt Analog
Authors: Wetterau Jörg
Published: September 2018

Roboter, Digitalisierung, Internet der Dinge, vernetzte Geräte und Datensicherheit verändern Labore. Die Fachmessen Analytica im April in München und Achema im Juni in Frankfurt zeigten Trends und Fortschritte bei der Laborautomation.
Umbrüche beim Kunststoffrecycling
Authors: Probst Thomas U.
Published: September 2018

Die europäische Kunststoffstrategie hat dem Recycling größere Aufmerksamkeit in Politik und Öffentlichkeit verschafft. Es gibt dadurch deutliche Marktveränderungen – nicht zuletzt getrieben vom Abfalleinfuhrstopp der Volksrepublik China.
Chemiegeschäfte digitalisieren
Authors: Bürger Christian
Published: September 2018

Die Chemiebranche wandelt ihre Geschäftsprozesse von klassischen Strukturen und Methoden hin zu digitalen Alternativen. Dabei werden immer mehr Daten online verfügbar, die es zu nutzen gilt.
Chemiedidaktik: "For Secret Writing can be used ..."
Authors: Ducci Matthias
Published: September 2018

Macht Geheimdienstarbeit paranoid? Die Central Intelligence Agency, CIA, hat Dokumente über Geheimtinten mit teilweise trivialen chemischen Rezepturen mehr als 90 Jahre lang geheim gehalten. Die Antwort muss daher mindestens „möglicherweise“ lauten. Für den Chemieunterricht liefern diese Dokumente und andere historische Schriften Anreize, chemische Reaktionen in einem Zusammenhang zu thematisieren, der Lernende motiviert.
Personalpolitik befriedigend
Authors: Bick Torid
Published: September 2018

Übernahmen in der chemischen Industrie verunsichern Akademiker.
Not as easy as π: An insertional residue does not explain the π‐helix gain‐of‐function in two‐component FMN reductases
Authors: McFarlane Jeffrey S. , Hagen Richard A. , Chilton Annemarie S. , Forbes Dianna L. , Lamb Audrey L. , Ellis Holly R.
Published: September 2018

The π‐helix located at the tetramer interface of two‐component FMN‐dependent reductases contributes to the structural divergence from canonical FMN‐bound reductases within the NADPH:FMN reductase family. The π‐helix in the SsuE FMN‐dependent reductase of the alkanesulfonate monooxygenase system has been proposed to be generated by the insertion of a Tyr residue in the conserved α4‐helix. Variants of Tyr118 were generated, and their X‐ray crystal structures determined, to evaluate how these alterations affect the structural integrity of the π‐helix. The structure of the Y118A SsuE π‐helix was converted to an α‐helix, similar to the FMN‐bound members of the NADPH:FMN reductase family. Although the π‐helix was altered, the FMN binding region remained unchanged. Conversely, deletion of Tyr118 disrupted the secondary structural properties of the π‐helix, generating a random coil region in the middle of helix 4. Both the Y118A and Δ118 SsuE SsuE variants crystallize as a dimer. The MsuE FMN reductase involved in the desulfonation of methanesulfonates is structurally similar to SsuE, but the π‐helix contains a His insertional residue. Exchanging the π‐helix insertional residue of each enzyme did not result in equivalent kinetic properties. Structure‐based sequence analysis further demonstrated the presence of a similar Tyr residue in an FMN‐bound reductase in the NADPH:FMN reductase family that is not sufficient to generate a π‐helix. Results from the structural and functional studies of the FMN‐dependent reductases suggest that the insertional residue alone is not solely responsible for generating the π‐helix, and additional structural adaptions occur to provide the altered gain of function.
Morphology of the petrosal and stapes of Borealestes (Mammaliaformes, Docodonta) from the Middle Jurassic of Skye, Scotland
Authors: Panciroli Elsa , Schultz Julia A. , Luo Zhe‐Xi
Published: September 2018

We describe, in unprecedented detail, the petrosals and stapes of the docodont Borealestes from the Middle Jurassic of Scotland, using high resolution μCT and phase‐contrast synchrotron imaging. We describe the inner ear endocast and the vascularized interior structure of the petrosal, and provide the first endocranial view of a docodontan petrosal. Our study confirms some similarities in petrosal and stapedial morphology with the better known Haldanodon of the Late Jurassic of Portugal, including: (1) the degree of curvature of the cochlea; (2) multiple features related to the highly pneumatized paroccipital region; (3) the shape of lateral trough, the fossa of the M. tensor tympani, and the ridge on the promontorium; (4) the round shape of the fenestra vestibuli; and (5) overall morphology of the stapes. But Borealestes differs from Haldanodon in having a bony ridge that separates the tympanic opening of the prootic canal, the secondary facial foramen and the hiatus Fallopii, from the fenestra vestibuli. We identify two new vascular structures: the anterior and posterior trans‐cochlear sinuses, which traverse the pars cochlearis around the cochlear nerve (VIII). These trans‐cochlear sinuses have not been observed in previous docodont specimens, and could be an autapomorphy of Borealestes, or apomorphic for this clade. We also establish the anatomical relationship of the circum‐promontorium plexus to the inner endocast. The high quality of our scans has made these structures visible for the first time.
Complex Dome Growth at Campi Flegrei Caldera (Italy) in the Last 15 ka
Authors: Marturano A. , Isaia R. , Aiello G. , Barra D.
Published: September 2018

The Campi Flegrei caldera (Italy) is an active volcanic system characterized by significant long‐ and short‐term ground deformation phenomena ranging the maxima values in the central sector of the caldera, where La Starza marine terrace is located. A detailed study of the La Starza provided crucial clues for understanding the resurgence of the central sector of the caldera following the 15‐ka Neapolitan Yellow Tuff eruption. The doming of the caldera floor, marked by two primary episodes of uplift, began soon after the collapse of about 110 m following the eruption. The first doming (15–9.2 ka) occurred as a response to loss of lithostatic loading producing magma influx, possibly regulated by thermal magmatic convection and chaotic movement inside the magma reservoir under the caldera. The calculated ~90 m of structural uplift is the persistent displacement correlated with magma volumes intruded accompanying the contemporaneous volcanic activity. The second episode of uplift (5.5–3.8 ka) produced a ground deformation pattern similar to that measured during recent unrest crises suggesting a stable and shallow (~4‐km deep) source of strain like a sill in an elastic half space. By this geometry and inversion of surface deformation, the volume of intruded material was determined. Simply varying pressure history as input, the time history of the surface deformation was reproduced by using spherical source geometry with a concentric viscoelastic shell 8‐km deep. The satisfactory comparison between the two models is a useful indication for interpreting the current unrest phase at the Campi Flegrei caldera.
Modeling the Effect of Moss Cover on Soil Temperature and Carbon Fluxes at a Tundra Site in Northeastern Siberia
Authors: Park Hotaek , Launiainen Samuli , Konstantinov Pavel Y. , Iijima Yoshihiro , Fedorov Alexander N.
Published: September 2018

Mosses strongly affect water and heat fluxes due their high water holding capacity and the provision of insulation. A land surface model (the coupled hydrological and biogeochemical process model, CHANGE) was used to quantitatively assess the influence of moss cover on soil temperature (TSOIL), active layer thickness (ALT), and ecosystem carbon balance. The CHANGE model was coupled with a moss process module, enabling the explicit representation of heat, water, and carbon exchange in the atmosphere‐vegetation‐moss‐soil system. The model was applied to a tundra site in northeastern Siberia over the period of 1980–2013. The results were validated with in situ observations and indicated a high level of insulation by the moss, resulting in warmer winter and cooler summer TSOIL and smaller ALT. The sensitivities of TSOIL and ALT to moss coverage and thickness were examined using model experiments. An increase in moss thickness lowered the summer TSOIL by 0.9–2.1 °C and reduced ALT by 9–20 cm compared with a moss‐free experiment. The moss‐induced cooler TSOIL in the root zone could limit the productivity of vegetation by reducing water availability to plant roots due to the presence of ice. This limitation increased with increasing moss layer thickness and coverage. The productivity of the moss itself increased with thickness, partially offsetting the reduction in vegetation productivity. Our modeling study suggests that the moss layer has a significant impact on TSOIL, ALT, and carbon balance in the Arctic tundra and may play an important role in future Arctic warming.
Hydrazone-based covalent organic frameworks for Lewis acid catalysis
Authors: Kundu Tanay , Wang Jian , Cheng Youdong , Du Yonghua , Qian Yuhong , Liu Guoliang , Zhao Dan
Published: September 2018

Two new hydroxy-rich hydrazone COFs are synthesized and postsynthetically incorporated with CoII to exhibit Lewis acid catalytic activity in cyanosilylation reactions of various aldehydes.
Synthesis, photophysical and electrochemical properties and DSSC application of triphenylaminochalcone cored dendrimers with anthracene and pyrene as surface groups and triazolylcholanoate as the bridging unit
Authors: Anandkumar Devaraj , Rajakumar Perumal
Published: September 2018

Triphenylaminochalcone-cored dendrimers decorated with anthracene and pyrene at the periphery have been synthesized by a convergent methodology using a click chemistry approach and characterized from spectral data and elemental analyses.
N-Doped graphene with anchored ZnFe2O4 nanostructures as an anode for lithium ion batteries with enhanced reversible capacity and cyclic performance
Authors: Navadeepthy Dhandapani , Bhuvaneswari Subramani , Prakash Raju , Viswanathan Chinnusamy , Ponpandian Nagamony
Published: September 2018

The challenges in developing more efficient lithium ion (Li-ion) batteries as a power source have been the subject of tremendous research due to the increase in demand for high-power unplugged electronics.
Enzymatic activity of Fe-grafted mesoporous silica nanoparticles: an insight into H2O2and glucose detection
Authors: Aghayan M. , Mahmoudi A. , Sazegar M. Reza , Ghavidel Hajiagha N. , Nazari K.
Published: September 2018

Iron-grafted MSNs were synthesized by post-synthesis and applied as a biosensor for detection of glucose and H2O2.
New high step‐up two‐input‐single‐output converter with low‐voltage stresses on switches and zero input currents ripple
Authors: Chavoshipour Heris Pedram , Saadatizadeh Zahra , Babaei Ebrahim , Sabahi Mehran
Published: September 2018

This study proposes a new non‐isolated high‐step‐up two‐input‐single‐output DC–DC converter with the capability of cancelling input currents ripples. The proposed converter has low‐voltage stresses on switches and diodes. Furthermore, it consists of two three‐winding‐coupled inductors connected with voltage multiplier cells. The voltage gain of the proposed converter can be increased by adding the second windings’ turns’ ratio or increasing the number of voltage multiplier cells. The third windings of coupled inductors, which are in series with capacitors at the input part of each boost stage are used to eliminate the ripples of input currents for the whole range of duty cycles. The proposed structure is a kind of two‐phase converter that can be used as an interleaved converter with one‐input‐one‐output terminals. In this study, the proposed converter is analysed during all operating modes and the voltage and current stresses of switches and diodes, voltage gain, required condition for cancelling input currents ripple are calculated. Moreover, in order to reconfirm theoretical analysis, EMTDC/PSCAD simulation and experimental results are presented.
Optimised planning of distribution network with photovoltaic system, battery storage, and DSTATCOM
Authors: Roy Ghatak Sriparna , Sannigrahi Surajit , Acharjee Parimal
Published: September 2018

In this circumstance of global warming, energy market deregulation, and enormous load growth, distribution network entails a proficient strategy to maintain the reliability and efficiency of the power service. Incorporation of solar photovoltaic (PV) system and battery storage (BS) in coordination with distributed static compensator (DSTATCOM) is a competent and practical approach to alleviate the power quality and reliability concern. In this study, a comprehensive strategic model is presented to optimally deploy PV, BS, and DSTATCOM to maximise voltage profile improvement, reliability, economic, and ecological benefit of the network. An accurate and precise novel voltage profile improvement indicator namely network voltage profile improvement index is proposed. Benefit–cost ratio and environment benefit index are proposed to quantify economic and environmental benefits, respectively. Similarly, reliability indices such as expected energy not served are used to appraise the system reliability. A fuzzy based extended version of NSGA II is utilised for the optimal deployment of the devices considering security limits. The proposed method is tested on 33‐bus and 69‐bus distribution networks considering time variant practical load models and the obtained results validate the efficacy and efficiency of the proposed method when compared with other multi‐objective algorithms.
Near‐domain‐based fault diagnosis approach for wireless sensor networks
Authors: Wang Hualin , Wang Zhile , Lu Min , Zhou Luyang
Published: September 2018

This study presents a near‐domain‐based diagnosis algorithm for wireless sensor networks nodes. The whole network is clustered to adapt to dynamic topologies, then self‐diagnosis procedure is started simultaneously on all nodes when a new cycle is initiated, or an abnormal behaviour is detected. Matching with neighbour nodes at most twice, the status of a node can be diagnosed. Wireless link fault between nodes is particularly considered in this study which may lead to the erroneous diagnosis of node status. Theoretical analysis and simulation results show that the proposed method has a high accuracy of fault diagnosis and a less communication traffic between nodes, thus greatly reducing energy consumption. At the same time, a high robustness is maintained in this novel fault diagnosis algorithm.
A bright approach to geochronology
Authors: Chamberlain Elizabeth L.
Published: September 2018

Optical dating uses light signals emitted from buried sediment grains to measure how long those grains were underground.
Movements and dive behaviour of a toothfish-depredating killer and sperm whale
Authors: Towers Jared R , Tixier Paul , Ross Katherine A , Bennett John , Arnould John P Y , Pitman Robert L , Durban John W
Published: September 2018

Depredation of demersal longlines by killer and sperm whales is a widespread behaviour that impacts fisheries and whale populations. To better understand how depredating whales behave in response to fishing activity, we deployed satellite-linked location and dive-profile tags on a sperm and killer whale that were depredating Patagonian toothfish from commercial longlines off South Georgia. The sperm and killer whale followed one fishing vessel for >180 km and >300 km and repeatedly depredated when longlines were being retrieved over periods of 6 and 7 d, respectively. Their behaviours were also sometimes correlated with the depths and locations of deployed gear. They both dove significantly deeper and faster when depredating compared with when foraging naturally. The killer whale dove >750 m on five occasions while depredating (maximum: 1087 m), but these deep dives were always followed by long periods (3.9–4.6 h) of shallow (<100 m) diving. We hypothesize that energetically and physiologically costly dive behaviour while depredating is driven by intra- and inter-specific competition due to the limited availability of this abundant resource.
Ecological best practice in decommissioning: a review of scientific research
Authors: Fortune I S , Paterson D M
Published: September 2018

The Oslo and Paris Commissions (OSPAR) decision 98/3 prohibits the dumping of man-made structures (MMS) offshore. However, there are regions of the world where MMS are recognized as providing an ecological and societal benefit through the provision of ecosystem goods and services. This review provides a commentary on our current understanding of the ecological influence of man-made structures, the consequences of their decommissioning and recognizes that our knowledge is far from complete. It is known that a diverse and complex ecosystem of attached organisms develops on submerged structures which supports a localized food web that could not exist without them. However, our lack of detailed information makes modelling of system response to decommissioning very tentative. Ideally, we should use the best possible scientific information to reach a consensus as to whether the blanket removal of MMS (excepting derogations) is the most environmentally supportable option. The evidence available to-date shows both benefits and some risk in leaving MMS in place and this needs to be examined without preconception. On the UKCS, MMS as artificial habitats are not considered under the Habitats Directive, irrespective of the value or rarity of the species present. We conclude that a more comprehensive regulatory process, together with the recognition of the ecology associated with man-made structures, would allow science to play a role in the decision-making rather than supporting a blanket policy ignoring ecological context.
Defining the Minimal Clinically Important Difference for Patients With Vestibular Schwannoma: Are all Quality-of-Life Scores Significant?
Authors: Kerezoudis Panagiotis , Yost Kathleen J , Tombers Nicole M , Celda Maria Peris , Carlson Matthew L , Link Michael J
Published: September 2018

BACKGROUND

The diagnosis of vestibular schwannomas (VS) is associated with reduced patient quality of life (QOL). Minimal clinically important difference (MCID) was introduced as the lowest improvement in a patient-reported outcome (PRO) score discerned as significant by the patient. We formerly presented an MCID for the Penn Acoustic Neuroma QOL (PANQOL) battery based on cross-sectional data from 2 tertiary referral centers.

OBJECTIVE

To validate the PANQOL MCID values using prospective data.

METHODS

A prospective registry capturing QOL was queried, comprising patients treated at the authors’ institution and Acoustic Neuroma Association members. Anchor- and distribution-based techniques were utilized to determine the MCID for domain and total scores. We only included anchors with Spearman's correlation coefficient larger than 0.3 in the MCID threshold calculations. Most domains had multiple anchors with which to estimate the MCID.

RESULTS

A total of 1254 patients (mean age: 57.4 yr, 65% females) were analyzed. Anchor-based methods produced a span of MCID values (median, 25th-75th percentile) for each PANQOL domain and the total score: hearing (13.1, 13-16 points), balance (14, 14-19 points), pain (21, 20-28 points), face (25, 16-36 points), energy (16, 15-18 points), anxiety (16 [1 estimate]), general (13 [1 estimate]), and total (12.5, 10-15 points).

CONCLUSION

Current findings corroborate our formerly shared experience using multi-institutional, cross-sectional information. These MCID thresholds can serve as a pertinent outcome when deciphering the clinical magnitude of VS QOL endpoints in cross-sectional and longitudinal studies.
Evolution of populations expanding on curved surfaces
Authors: Beller Daniel A. , Alards Kim M. J. , Tesser Francesca , Mosna Ricardo A. , Toschi Federico , Mobius Wolfram
Published: September 2018

The expansion of a population into new habitat is a transient process that leaves its footprints in the genetic composition of the expanding population. How the structure: of the environment shapes the population front and the evolutionary dynamics during such a range expansion is little understood. Here, we investigate the evolutionary dynamics of populations consisting of many selectively neutral genotypes expanding on curved surfaces. Using a combination of individual-based off-lattice simulations, geometrical arguments, and lattice-based stepping-stone simulations, we characterise the effect of individual bumps on an otherwise flat surface. Compared to the case of a range expansion on a flat surface:, we observe a transient relative increase, followed by a decrease, in neutral genetic diversity at the population front. Ill addition, we find that individuals at the sides of the bump have a dramatically increased expected number of descendants, while their neighbours closer to the bump’s centre are far less lucky. Both observations can be explained using an analytical description of straight paths (geodesics) on the curved surface, Complementing previous studies of heterogeneous flat environments, the findings here build our understanding of how complex environments shape the evolutionary dynamics of expanding populations.
An antigenic atlas of HIV-1 escape from broadly neutralizing antibodies
Authors: Dingens Adam S. , Arenz Dana , Weight Haidyn , Overbaugh Julie , Bloom Jesse D.
Published: September 2018

Anti-HIV broadly neutralizing antibodies (bnAbs) have revealed vaccine targets on the virus’s Env protein and are themselves promising immunotherapeutics. The efficacy of bnAb-based therapies and vaccines depends in part on how readily the virus can escape neutralization. While structural studies can define contacts between bnAbs and Env, only functional studies can define mutations that confer escape. Here we map how all single amino-acid mutations to Env affect neutralization of HIV by nine bnAbs targeting five epitopes. For most bnAbs, mutations at only a small fraction of structurally defined contact sites mediated escape, and most escape occurred at sites that are near but do not directly contact the antibody. The mutations selected by two pooled bnAbs were similar to those expected from the combination of the bnAbs’ independent action. Overall, our mutation-level antigenic atlas provides a comprehensive dataset for understanding viral immune escape and refining therapies and vaccines.
Healthcare professionals' level of medication knowledge in Africa: a systematic review
Authors: Berhe Derbew Fikadu , Taxis Katja , Haaijer‐Ruskamp Flora M. , Mol Peter G. M.
Published: September 2018

Aims

Understanding how much healthcare professionals (HCPs) know about medication can help in devising strategies to improve rational medication use. This study aimed to synthesize information on the level of medication knowledge of HCPs in Africa.

Method

We performed a systematic literature study in Embase and PubMed. We included original studies quantifying HCPs' medication knowledge, published between 2012 and 2016. We extracted disease focus, country, number and type of HCPs included and all medication‐related knowledge questions and scored the quality of papers. The outcome measure was the percentage of HCPs who correctly answered medication knowledge questions.

Results

We identified 64 studies from 12 African countries, comprising 13 911 HCPs, mostly nurses/midwifes and physicians. We extracted 306 medication‐related knowledge questions, and only 52% (SD 28) of HCPs correctly answered them. Knowledge questions were mainly about medication prescribed for communicable diseases (70%), followed by non‐communicable diseases (11%), and family planning/gynaecology (10%). Most papers concluded that there was a considerable medication knowledge gap among HCPs.

Conclusion

We found a low level of medication knowledge across different disease areas, countries and HCPs. This underlines the continuous need to strengthen the undergraduate and postgraduate education in (clinical) pharmacology and therapeutics in Africa.
Risk factors for linezolid‐induced thrombocytopenia in patients without haemato‐oncologic diseases
Authors: Choi Go Wun , Lee Ju‐Yeun , Chang Min Jung , Kim Young Kyung , Cho Yoonsook , Yu Yun Mi , Lee Euni
Published: September 2018

This study aimed to describe the occurrence and to evaluate the predictive factors of thrombocytopenia caused by parenteral linezolid in hospitalised patients without haemato‐oncologic diseases. Using electronic medical records, a retrospective safety evaluation was performed among all hospitalised adult patients who received parenteral linezolid therapy between January 2005 and June 2016. Of all identified 264 patients with an average age of 63.4 (SD 15.8) years, thrombocytopenia occurred at a rate of 29.2% after an average of 11.2 (SD 7.4) days of the initiation of linezolid therapy. Significant predictive factors for thrombocytopenia included the duration of linezolid therapy longer than or equal to 7 days (adjusted odds ratios [ORs] 7.25, 19.51 and 28.80; 95% confidence intervals [CIs] 1.92‐27.38, 4.76‐79.95 and 6.48‐127.92 for 7‐13 days, 14‐20 days and ≥21 days, respectively; P < 0.01 for all values), baseline platelet count <150 × 103/mm3 (adjusted OR, 5.08; 95% CI, 2.06‐12.55; P < 0.001), creatinine clearance <30 mL/min (adjusted OR, 4.19; 95% CI, 1.59‐11.06; P = 0.004) and concurrent low‐dose aspirin therapy (adjusted OR, 2.99; 95% CI, 1.26‐7.08; P = 0.013). Baseline platelet count less than 150 × 103/mm3 was an independent predictor of early‐onset (≤6 days) thrombocytopenia (adjusted OR, 5.07; 95% CI, 1.46‐17.58; P = 0.011). Closer monitoring of platelet count is required in patients who receive parenteral linezolid therapy for 7 days or more, and have low baseline platelet counts or impaired renal function.
Revising the Bantu tree
Authors: Whiteley Peter M. , Xue Ming , Wheeler Ward C.
Published: September 2018

Phylogenetic methods offer a promising advance for the historical study of language and cultural relationships. Applications to date, however, have been hampered by traditional approaches dependent on unfalsifiable authority statements: in this regard, historical linguistics remains in a similar position to evolutionary biology prior to the cladistic revolution. Influential phylogenetic studies of Bantu languages over the last two decades, which provide the foundation for multiple analyses of Bantu sociocultural histories, are a major case in point. Comparative analyses of basic lexica, instead of directly treating written words, use only numerical symbols that express non‐replicable authority opinion about underlying relationships. Building on a previous study of Uto‐Aztecan, here we analyse Bantu language relationships with methods deriving fromDNAsequence optimization algorithms, treating basic vocabulary as sequences of sounds. This yields finer‐grained results that indicate major revisions to the Bantu tree, and enables more robust inferences about the history of Bantu language expansion and/or migration throughout sub‐Saharan Africa. “Early‐split” versus “late‐split” hypotheses for East and West Bantu are tested, and overall results are compared to trees based on numerical reductions of vocabulary data. Reconstruction of language histories is more empirically based and robust than with previous methods.
Early Marriage, Social Networks and the Transmission of Norms
Authors: Asadullah M. Niaz , Wahhaj Zaki
Published: September 2018

We investigate whether female early marriage is a conduit for the transmission of social norms, specifically norms relating to gender roles and rights within the household. We exploit differences in age at menarche between sisters as an exogenous source of variation in marriage age. This approach allows us to control for beliefs and attitudes that are transmitted from parents to children. Using a sample of unmarried adolescents, we first show that the timing of menarche has no direct effect on adolescent attitudes towards gender norms. Yet we find that early marriage increases agreement with statements supportive of traditional gender roles and gender bias in the allocation of resources. We also find some evidence that early marriage worsens the (self‐reported) quality of a woman's post‐marital social network.
Diagnosis and management of PNH: Review and recommendations from a Belgian expert panel
Authors: Devos Timothy , Meers Stef , Boeckx Nancy , Gothot Andre , Deeren Dries , Chatelain Bernard , Chatelain Christian , Devalet Bérangère
Published: September 2018

Despite its considerable morbidity and mortality, paroxysmal nocturnal haemoglobinuria (PNH) is still underdiagnosed. Patients with PNH can suffer from cardiovascular, gastrointestinal, neurological or haematological symptoms and refer to several specialists. The aim of this paper is to review the diagnosis and the management of PNH patients, with the primary focus on identifying high‐risk groups. Additionally, the implementation and prognostic value of the defined high‐risk groups will be commented on and the management of PNH patients is discussed from a Belgian perspective. Finally, based on the available data, recommendations are provided. Eculizumab is a potent C5 complement inhibitor and reduces intravascular haemolysis and thrombosis in PNH patients and improves their quality of life. As thrombosis is the main cause of death in PNH patients, identifying high‐risk PNH patients in need of therapy is essential. Currently, novel complement inhibitors are in development and the first data seem promising. Another challenge in PNH is to identify new markers to assess the thrombotic risk to achieve a better risk‐based prophylactic anti‐thrombotic management. Finally, because of the low prevalence of the disease, PNH patients should be included in the prospective PNH registry, which will offer new insights on the natural course of the disease and the impact of treatment of PNH.
Deceleration of glycometabolism impedes IgG‐producing B‐cell‐mediated tumor elimination by targeting SATB1
Authors: Liu Jiajing , Li Yifan , Lu Zhou , Gu Jie , Liang Yun , Huang Enyu , Wang Zhiming , Zhang Hushan , Wang Luman , Zhang Dan , Yu Hongxiu , Liu Ronghua , Chu Yiwei
Published: September 2018

B lymphocytes, known as antibody producers, mediate tumor cell destruction in the manner of antibody‐dependent cell‐mediated cytotoxicity; however, their anti‐tumor function seems to be weakened during tumorigenesis, while the underlying mechanisms remain unclear. In this study, we found that IgG mediated anti‐tumor effects, but IgG‐producing B cells decreased in various tumors. Considering the underlying mechanism, glycometabolism was noteworthy. We found that tumor‐infiltrating B cells were glucose‐starved and accompanied by a deceleration of glycometabolism. Both inhibition of glycometabolism and deprivation of glucose through tumor cells, or glucose‐free treatment, reduced the differentiation of B cells into IgG‐producing cells. In this process, special AT‐rich sequence‐binding protein‐1 (SATB1) was significantly silenced in B cells. Down‐regulating SATB1 by inhibiting glycometabolism or RNA interference reduced the binding of signal transducer and activator of transcription 6 (STAT6) to the promoter of germline Cγ gene, subsequently resulting in fewer B cells producing IgG. Our findings provide the first evidence that glycometabolic inhibition by tumorigenesis suppresses differentiation of B cells into IgG‐producing cells, and altering glycometabolism may be promising in improving the anti‐tumor effect of B cells.
Job-exposure matrices addressing lifestyle to be applied in register-based occupational health studies
Authors: Bondo Petersen Sesilje , Flachs Esben Meulengracht , Prescott Eva Irene Bossano , Tjønneland Anne , Osler Merete , Andersen Ingelise , Juel Knud , Budz-Jørgensen Esben , Kolstad Henrik A , Schlünssen Vivi , Bonde Jens Peter
Published: September 2018

Objectives

Information about lifestyle factors in register-based occupational health studies is often not available. The objective of this study was therefore to develop gender, age and calendar-time specific job-exposure matrices (JEMs) addressing five selected lifestyle characteristics across job groups as a tool for lifestyle adjustment in register-based studies.

Methods

We combined and harmonised questionnaire and interview data on lifestyle from several Danish surveys in the time period 1981–2013 for 264 054 employees registered with a DISCO-88 code (the Danish version of International Standard Classification of Occupations (ISCO)-88) in a nationwide register-based Danish Occupational Cohort. We modelled the probability of specified lifestyles in mixed models for each level of the four-digit DISCO code with age and sex as fixed effects and assessed variation in terms of intraclass correlation coefficients (ICCs) and exposure-level percentile ratios across jobs for six different time periods from 1981 through 2013.

Results

The ICCs were overall low (0.26%–7.05%) as the within-job group variation was large relative to the between job group variation, but across jobs the calendar period-specific ratios between highest and lowest predicted levels were ranging from 1.2 to 6.9, and for the 95%/1% and the 75%/5% percentile ratios ranges were 1.1–2.8 and 1.1–1.6, respectively, thus indicating substantial contrast for some lifestyle exposures and some occupations.

Conclusions

The lifestyle JEMs may prove a useful tool for control of lifestyle-related confounding in register-based occupational health studies where lacking information on individual lifestyle factors may compromise internal validity.
Neglected exposure route: cobalt on skin and its associations with urinary cobalt levels
Authors: Kettelarij Jolinde , Midander Klara , Lidén Carola , Bottai Matteo , Julander Anneli
Published: September 2018

Objectives

Cobalt (Co) exposure is associated with adverse health effects including skin sensitisation, asthma and interstitial lung fibrosis. Exposure to Co in industrial settings is often assessed using air samples or biomonitoring in urine. Skin exposure is rarely measured. Aim of this study was to quantify and compare the importance of Co skin exposure and respiratory exposure in determining urinary Co concentrations.

Methods

Co skin exposure was measured in 76 hard metal workers by acid wipe sampling before and at the end of work shifts. Spot urine was collected during a 24-hour period from the start of a shift. Respiratory exposure was measured by personal inhalable dust sampling during a shift in 30 workers. Co was analysed by inductively coupled plasma mass spectrometry.

Results

Quantile regression modelling showed that a doubling of Co on skin before or at the end of shift increased the median urinary concentration of Co by 70% (p<0.001) or 32% (p<0.001), respectively. A doubling of Co in air increased median urinary Co by 38% (p<0.001). Co skin exposures were still significantly associated with urinary Co after excluding a group of workers with high respiratory exposure (33%, p=0.021 and 17%, p=0.002).

Conclusions

The results indicate an association between Co skin exposure and urinary Co concentrations. This should be considered when using urinary Co as a biomarker of exposure.
“Beyond the Great Story” of War and Revolution
Authors: Rosenberg William G.
Published: September 2018

This essay looks at the ways our understanding of the Russian revolution was conditioned by contemporary narratives of progress and change, and how these narratives and the “historical imaginations” that created them also influenced later tellings of the “great story.” In this way it attempts to reposition the grave problems Russia faced especially after 1914 in terms of the actual and proposed solutions offered by historical actors, and evaluates their effectiveness as well as their relation especially to the evolving meanings of revolution. In the process, it emphasizes the subjective aspects of problems like scarcity and personal loss, and how these might not have been amenable to the rational logics of state administration.
Assessing and Improving Operational Strategies for the Benefit of Passengers in Rail-Bound Urban Transport Systems
Authors: Durand Anne , Van Oort Niels , Hoogendoorn Serge
Published: September 2018

Unplanned disruptions in transit can have consequent impacts on passengers. The more inconvenienced passengers are, the more likely operators will be negatively impacted. Yet so far, operators and researchers have addressed the rescheduling problem during disruptions mainly with a supply-side focus – timetable, crews, and vehicles – and not with a passenger perspective. Urban rail transit particularly lacks insights in terms of passenger-focused rescheduling. Being able to assess the inconvenience experienced by passengers during disruptions compared with what they normally experience, and being able to compare how different rescheduling strategies affect them are therefore two major challenges. The framework developed in this study precisely aims at tackling these challenges. A case study of the Rotterdam Metro is used to test the framework developed in this paper. Alternative strategies are developed focusing on the incident phase (from the beginning of the incident until its cause is resolved). The application of the framework reveals that a regularity-focused rescheduling strategy would be beneficial for high-frequency service users. Realistically, yearly savings could amount to around €900,000 in terms of societal passenger costs for the operator in the Rotterdam area alone. However, the omnipresence of the punctuality paradigm, through which most operators plan and analyze operations, makes the implementation of passenger-focused strategies a challenging task for traffic controllers. The results of the study are valuable for transit operators worldwide, and the framework could provide decision makers with insights on the performance of different strategies, bringing to light trade-offs between the supply and passenger sides during disruptions.
Development of a Crash Risk-Scoring Tool for Pedestrian and Bicycle Projects in Oregon
Authors: Wang Yi , Monsere Christopher M. , Chen Chen , Wang Haizhong
Published: September 2018

Methods for identifying and prioritizing high-crash locations for safety improvements are generally crash-based. There are fewer reported crashes involving non-motorized users and, in most states, reported crashes must involve a motor vehicle. This means that minor, non-injury events are not reported and those crashes that are reported tend to be more severe. Selecting projects based only on crash performance is sometimes limiting for these crash types and predicting where these crashes will occur next is also a challenging task. An alternative to crash-based selection is to develop risk-based criteria and methods. This paper presents the results of a research effort to develop a risk-scoring method with weights derived from data for use in project screening and selection in Oregon. To develop the risk model, data were collected from 188 segments and 184 intersections randomly selected on both state and non-state roadways. Geometric, land use, volume, and crash data were collected from Google Earth, EPA’s Smart Location Database, and the Oregon Department of Transportation crash database from 2009 to 2013. The sample included 213 bicycle and pedestrian crashes on the segments and 238 at intersections. Logistic regression models were developed and the outputs used to create pedestrian and bicycle risk-scoring tools for segments and intersections. The risk-scoring tool was applied to safety projects identified in the 2015 All Roads Transportation Safety (ARTS) project lists from Oregon. The risk scores for the case study applications aligned reasonably well with the project’s benefits-costs estimates.
Glycopyrrolate/eFlow CS: The First Nebulized Long-Acting Muscarinic Antagonist Approved to Treat Chronic Obstructive Pulmonary Disease
Authors: Pleasants Roy A.
Published: September 2018

Objective: To review the pharmacology, efficacy, and safety of the first nebulized long-acting muscarinic antagonist (LAMA), glycopyrrolate (GLY)/eFlow closed system (CS) nebulizer, approved for maintenance treatment of chronic obstructive pulmonary disease (COPD). Data Sources: A PubMed search was conducted (January 2000 to July 2018) using the following terms/phrases: nebulized glycopyrrolate, inhalation devices in COPD, long-acting muscarinic antagonists COPD, and COPD survey. Retrieved articles were reviewed to identify additional references. Study Selection and Data Extraction: Primary and review articles on GLY/eFlow CS and other treatment options for patients with COPD were selected. Data Synthesis: Guidelines recommend the use of LAMAs, alone or in combination with long-acting β2-agonists, as maintenance therapy for the majority of patients with COPD. With the range of different devices and bronchodilators now available, treatment can be tailored based on individual needs. The eFlow CS nebulizer delivers GLY rapidly over a 2- to 3-minute period and provides bronchodilation within 30 minutes, lasting 12 hours. Phase 2 dose-finding and phase 3 studies demonstrated sustained statistically significant and clinically important improvements in pulmonary function and patient-reported outcomes with GLY/eFlow CS. Relevance to Patient Care and Clinical Practice: GLY/eFlow CS provides a novel, portable, efficient, and rapid drug delivery system. Conclusions: The recently approved GLY/eFlow CS drug-device combination provides a viable treatment option for patients with COPD, particularly those with conditions that may impair proper use of traditional handheld inhalers.