bluuebunny/crossref_metadata_2025 huggingface dataset:
Phased implementation of spaced clinic visits for stable HIV‐positive patients in Rwanda to support Treat All
Authors: Nsanzimana Sabin , Remera Eric , Ribakare Muhayimpundu , Burns Tracy , Dludlu Sibongile , Mills Edward J , Condo Jeanine , Bucher Heiner C , Ford Nathan
Published: July 2017

Introduction: In 2016, Rwanda implemented “Treat All,” requiring the national HIV programme to increase antiretroviral (ART) treatment coverage to all people living with HIV. Approximately half of the 164,262 patients on ART have been on treatment for more than five years, and long‐term retention of patients in care is an increasing concern. To address these challenges, the Ministry of Health has introduced a differentiated service delivery approach to reduce the frequency of clinical visits and medication dispensing for eligible patients. This article draws on key policy documents and the views of technical experts involved in policy development to describe the process of implementation of differentiated service delivery in Rwanda.

Discussion: Implementation of differentiated service delivery followed a phased approach to ensure that all steps are clearly defined and agreed by all partners. Key steps included: definition of scope, including defining which patients were eligible for transition to the new model; definition of the key model components; preparation for patient enrolment; considerations for special patient groups; engagement of implementing partners; securing political and financial support; forecasting drug supply; revision, dissemination and implementation of ART guidelines; and monitoring and evaluation.

Conclusions: Based on the outcomes of the evaluation of the new service delivery model, the Ministry of Health will review and strategically reduce costs to the national HIV program and to the patient by exploring and implementing adjustments to the service delivery model.
High rates of retention and viral suppression in the scale‐up of antiretroviral therapy adherence clubs in Cape Town, South Africa
Authors: Tsondai Priscilla Ruvimbo , Wilkinson Lynne Susan , Grimsrud Anna , Mdlalo Precious Thembekile , Ullauri Angelica , Boulle Andrew
Published: July 2017

Introduction: Increasingly, there is a need for health authority scale up of successfully piloted differentiated models of antiretroviral therapy (ART) delivery. However, there is a paucity of evidence on system‐wide outcomes after scale‐up. In the Cape Town health district, stable adult patients were referred to adherence clubs (ACs) – a group model of ART delivery with five visits per year. By the end of March 2015, over 32,000 ART patients were in an AC. We describe patient outcomes of a representative sample of AC patients during this scale‐up.

Methods: Patients enrolled in an AC at non‐research supported sites between 2011 and 2014 were eligible for analysis. We sampled 10% of ACs (n = 100) in quintets proportional to the number of ACs at each facility, linking each patient to city‐wide laboratory and service access data to validate retention and virologic outcomes. We digitized registers and used competing risks regression and cross‐sectional methods to estimate outcomes: mortality, transfers, loss to follow‐up (LTFU) and viral load suppression (≤400 copies/mL). Predictors of LTFU and viral rebound were assessed using Cox proportional hazards models.

Results: Of the 3216 adults contributing 4019 person years of follow‐up (89% in an AC, median 1.1 years), 70% were women. Retention was 95.2% (95% CI, 94.0‐96.4) at 12 months and 89.3% (95% CI, 87.1‐91.4) at 24 months after AC enrolment. In the 13 months prior to analysis closure, 88.1% of patients had viral load assessments and of those, viral loads ≤400 copies/mL were found in 97.2% (95% CI, 96.5‐97.8) of patients. Risk of LTFU was higher in younger patients and in patients accessing ART from facilities with larger ART cohorts. Risk of viral rebound was higher in younger patients, those that had been on ART for longer and patients that had never sent a buddy to collect their medication.

Conclusions: This is the first analysis reporting patient outcomes after health authorities scaled‐up a differentiated care model across a high burden district. The findings provide substantial reassurance that stable patients on long‐term ART can safely be offered care options, which are more convenient to patients and less burdensome to services.
Multi‐month prescriptions, fast‐track refills, and community ART groups: results from a process evaluation in Malawi on using differentiated models of care to achieve national HIV treatment goals
Authors: Prust Margaret L. , Banda Clement K. , Nyirenda Rose , Chimbwandira Frank , Kalua Thokozani , Jahn Andreas , Eliya Michael , Callahan Katie , Ehrenkranz Peter , Prescott Marta R. , McCarthy Elizabeth A. , Tagar Elya , Gunda Andrews
Published: July 2017

Introduction: In order to facilitate scale‐up of antiretroviral therapy (ART) in Malawi, innovative and pragmatic models have been developed to optimize the efficiency of HIV service delivery. In particular, three models of differentiated care have emerged for stable patients: adjusted appointment spacing through multi‐month scripting (MMS); fast‐track drug refills (FTRs) on alternating visits; and community ART groups (CAGs) where group members rotate in collecting medications at the facility for all members. This study aimed to assess the extent to which ART patients in Malawi are differentiated based on clinical stability and describe the characteristics and costs associated with the models of differentiated care offered.

Methods: A mixed methods process evaluation was conducted from 30 purposefully selected ART facilities. Cross‐sectional data for this evaluation was collected between February and May 2016. The following forms of data collection are reported here: structured surveys with 136 health care workers; reviews of 75,364 patient clinical records; 714 observations of visit time and flow; and 30 questionnaires on facility characteristics.

Results: Among ART patients, 77.5% (95% confidence interval [CI] 74.1–80.6) were eligible for differentiated models of care based on criteria for clinical stability from national guidelines. Across all facilities, 69% of patients were receiving MMS. In facilities offering FTRs and CAGs, 67% and 6% of patients were enrolled in the models, respectively. However, eligibility criteria were used inconsistently: 72.9% (95% CI 66.3–78.6) of eligible patients and 42.3% (95% CI 33.1–52.0) ineligible patients received MMS. Results indicated that patient travel and time costs were reduced by 67%, and the unit costs of ART service delivery through the MMS, FTR and CAG models were similar, representing a reduction of approximately 10% in the annual unit cost of providing care to stable patients that receive no model.

Conclusions: MMS is being implemented nationally and has already generated cost savings and efficiencies in Malawi for patients and the health system, but could be improved by more accurate patient differentiation. While expanding FTRs and CAGs may not offer significant further cost savings in Malawi, future studies should investigate if such alternative models lead to improvements in patient satisfaction or clinical outcomes that might justify their implementation.
Initiation into Teaching from the Perspective of Primary School Teachers: Differences Between Newly Qualified and Experienced Teachers
Authors: Cañón Rodríguez Ruth , Cantón Mayo Isabel , Arias Gago Ana Rosa , Baelo Álvarez Roberto
Published: July 2017

This study consists of an investigation into the experiences of new teachers in primary education in the province of León, during their initiation into teaching. The objective was to explore how they experience this stage, and to recognize the training needs that exist along with the degree of motivation and satisfaction expressed with the measures designed for integration into teaching. The methodology used is descriptive and interpretive, ex-post-facto oriented towards a search for improvement.

Research finding reveals the existence of significant gaps in initial teacher training that bears a negative influence on the subsequent professional development of the teachers involved. In this sense, the training programs designed for teachers who are initiating their career, although valued positively by both novices and experienced teachers; do not overcome their initial shortcomings.

Despite the difficulties, however, new teachers show a general feeling of satisfaction with the stage in which they initiate their teaching.
Actions and achievements of self-regulated learning in personal environments. Research on students participating in the Graduate Program in Preschool Education at the University of Granada
Authors: Chaves-Barboza Eduardo , Trujillo-Torres Juan Manuel , López-Núñez Juan Antonio , Sola-Martínez Tomás
Published: July 2017

This paper is intended to study the self-regulated learning (SRL) process in personal learning environments (PLEs) among students participating in the Graduate Program for Preschool Education at the University of Granada (Spain). The study is focused on self-regulatory actions carried out by students, and on their self-regulated learning achievements, during the phases of action and reflection of this process.

A Likert scale questionnaire was applied to a random cluster sample of the population. Descriptive and inferential statistical analyses were performed based on the collected data, as were non-parametric correlation and analysis of variance tests.

The results confirm the importance of individual learning in the self-regulated process, and highlight the importance of digital tools in all three phases of self-regulation. Furthermore, the results show that teachers’ suggestions are related to the use of digital tools and recording of reflections on the learning process, and establish relationships between learning management tools and cognitive and metacognitive processes. The results also permit classification of students into three subgroups, based on their achievements. Analyses are consistent with the theory that explains the cyclical nature of self-regulated learning and the influence of social relationships on individual self-regulatory processes.
The biophysical properties of plasmalogens originating from their unique molecular architecture
Authors: Koivuniemi Artturi
Published: July 2017

Plasmalogens are a unique class of phospholipids that are present in many organisms. Their presence in cell membranes has intrigued researchers for decades due to their unique molecular structure, namely the vinyl‐ether bond at the sn‐1 position, and their association with brain related disorders. Apparently, based on their amount in the cell membranes, their function is to provide exclusive structural and dynamical properties to these complex molecular assemblies. Yet, many of their physiological roles manifested through their biophysical properties have been challenging to identify. In this review, the biophysical properties of plasmalogens are discussed and compared to other lipid species. The role of plasmalogens is examined in the context of cell membrane function, and some future directions are given.
Regional sensitivities of seasonal snowpack to elevation, aspect, and vegetation cover in western North America
Authors: Tennant Christopher J. , Harpold Adrian A. , Lohse Kathleen Ann , Godsey Sarah E. , Crosby Benjamin T. , Larsen Laurel G. , Brooks Paul D. , Van Kirk Robert W. , Glenn Nancy F.
Published: July 2017

In mountains with seasonal snow cover, the effects of climate change on snowpack will be constrained by landscape‐vegetation interactions with the atmosphere. Airborne lidar surveys used to estimate snow depth, topography, and vegetation were coupled with reanalysis climate products to quantify these interactions and to highlight potential snowpack sensitivities to climate and vegetation change across the western U.S. at Rocky Mountain (RM), Northern Basin and Range (NBR), and Sierra Nevada (SNV) sites. In forest and shrub areas, elevation captured the greatest amount of variability in snow depth (16–79%) but aspect explained more variability (11–40%) in alpine areas. Aspect was most important at RM sites where incoming shortwave to incoming net radiation (SW:NetR↓) was highest (∼0.5), capturing 17–37% of snow depth variability in forests and 32–37% in shrub areas. Forest vegetation height exhibited negative relationships with snow depth and explained 3–6% of its variability at sites with greater longwave inputs (NBR and SNV). Variability in the importance of physiography suggests differential sensitivities of snowpack to climate and vegetation change. The high SW:NetR↓ and importance of aspect suggests RM sites may be more responsive to decreases in SW:NetR↓ driven by warming or increases in humidity or cloud cover. Reduced canopy‐cover could increase snow depths at SNV sites, and NBR and SNV sites are currently more sensitive to shifts from snow to rain. The consistent importance of aspect and elevation indicates that changes in SW:NetR↓ and the elevation of the rain/snow transition zone could have widespread and varied effects on western U.S. snowpacks.
Production, consumption, and migration of methane in accretionary prism of southwestern Taiwan
Authors: Chen Nai‐Chen , Yang Tsanyao Frank , Hong Wei‐Li , Chen Hsuan‐Wen , Chen Hsiao‐Chi , Hu Ching‐Yi , Huang Yu‐Chun , Lin Saulwood , Lin Li‐Hung , Su Chih‐Chieh , Liao Wei‐Zhi , Sun Chih‐Hsien , Wang Pei‐Ling , Yang Tao , Jiang Shao‐Yong , Liu Char‐Shine , Wang Yunshuen , Chung San‐Hsiung
Published: July 2017

To systematically quantify the production, consumption, and migration of methane, 210 sediment cores were collected from offshore southwestern Taiwan and analyzed for their gas and aqueous geochemistry. These data, combined with published results, were used to calculate the diffusive methane fluxes across different geochemical transitions and to develop scenarios of mass balance and constrain deep microbial and thermogenic methane production rates within the accretionary prism. The results showed that methane diffusive fluxes ranged from 2.71 × 10−3 to 2.78 × 10−1 and from –1.88 × 10−1 to 3.97 mmol m−2 d−1 at the sulfate‐methane‐transition‐zone (SMTZ) and sediment‐seawater interfaces, respectively. High methane fluxes tend to be associated with structural features, suggesting a strong structural control on the methane transport. A significant portion of ascending methane (>50%) is consumed by anaerobic oxidation of methane at the SMTZ at most sites, indicating effective biological filtration. Gas compositions and isotopes revealed a transition from the predominance of microbial methane in the passive margin to thermogenic methane at the upper slope of the active margin and onshore mud volcanoes. Methane production and consumption at shallow depths were nearly offset with a small fraction of residual methane discharged into seawater. The flux imbalance arose primarily due to the larger production of methane through deep microbial and thermogenic processes at a magnitude of 1512–43,096 Tg Myr−1 and could be likely accounted for by the sequestration of methane into hydrate forms, and clay absorption.
Modeling phase separation and phase change for magma ocean solidification dynamics
Authors: Boukaré C.‐E. , Ricard Y.
Published: July 2017

Just after accretion, the Earth's mantle was significantly molten by the heat dissipation due to large impacts and to the segregation of the core. The mineralogical observations and thermodynamics models of solid‐liquid equilibrium of silicates show that several types of crystallization may have happened at different depths in the mantle. Solids were probably formed first at the bottom of the lower mantle or at midmantle leaving two possible magma oceans, a shallow one and an abyssal one. Near the bottom of the mantle, the liquid phase might become denser than solids due to iron enrichment. In the shallow magma ocean, the crystallizing solid phase was denser and sank through the magma to settle and compact at depth. To understand these complex dynamics, we develop a two‐phase numerical code that can handle simultaneously convection in each phase and in the slurry, and the compaction or decompaction of the two phases. Although our code can only run in a parameter range (Rayleigh number, viscosity contrast between phases, Prandlt number) far from what would be realistic, we think it already provides a rich dynamics that illustrates what could have happened. We show situations in which the crystallization front is gravitationally stable and situations where the newly formed solids are gravitationally unstable and can snow across the magma. Our study suggests that the location of a density contrast between solid and magma must be considered of equal importance with that of the intersection between liquidus and isentrope for what concerns mantle solidification.
Spreading rate‐dependent variations in crystallization along the global mid‐ocean ridge system
Authors: Wanless V. Dorsey , Behn Mark D.
Published: July 2017

We investigate crustal accretion at mid‐ocean ridges by combining crystallization pressures calculated from major element contents in mid‐ocean ridge basalt (MORB) glasses and vapor‐saturation pressures from melt inclusions and MORB glasses. Specifically, we use established major element barometers and pressures estimated from 192 fractional crystallization trends to calculate crystallization pressures from >9000 MORB glasses across the global range of mid‐ocean ridge spreading rates. Additionally, we estimate vapor‐saturation pressures from >400 MORB glasses from PETDB and >400 olivine‐hosted melt inclusions compiled from five ridges with variable spreading rates. Both major element and vapor‐saturation pressures increase and become more variable with decreasing spreading rate. Vapor saturation pressures indicate that crystallization occurs in the lower crust and upper mantle at all ridges, even when a melt lens is present. We suggest that the broad peaks in major element crystallization pressures at all spreading rates reflects significant crystallization of on and off‐axis magmas along the base of a sloping lithosphere. Combining our observations with ridge thermal models we show that crystallization occurs over a range of pressures at all ridges, but it is enhanced at thermal/rheologic boundaries, such as the melt lens and the base of the lithosphere. Finally, we suggest that the remarkable similarity in the maximum vapor‐saturation pressures (∼3 kbars) recorded in melt inclusions from a wide range of spreading rates reflects a relatively uniform CO2 content of 50–85 ppm for the depleted upper mantle feeding the global mid‐ocean ridge system.
Temperature dependence of stable carbon kinetic isotope effect for the oxidation reaction of ethane by OH radicals: Experimental and theoretical studies
Authors: Piansawan T. , Saccon M. , Vereecken L. , Gensch I. , Kiendler‐Scharr A.
Published: July 2017

The stable carbon kinetic isotope effect (KIE) of ethane photooxidation by OH radicals was deduced by employing both laboratory measurements and theoretical calculations. The investigations were designed to elucidate the temperature dependence of KIE within atmospherically relevant temperature range. The experimental KIE was derived from laboratory compound‐specific isotope analyses of ethane with natural isotopic abundance exposed to OH at constant temperature, showing ε values of 7.16 ± 0.54‰ (303 K), 7.45 ± 0.48‰ (288 K), 7.36 ± 0.28‰ (273 K), 7.61 ± 0.28‰ (263 K), 8.89 ± 0.90‰ (253 K), and 9.42 ± 2.19‰ (243 K). Compared to previous studies, a significant improvement of the measurement precision was reached at the high end of the investigated temperature range. The KIE was theoretically determined as well, in the temperature range of 150 K to 400 K, by calculating the reaction rate coefficients of 12C and singly 13C substituted ethane isotopologues applying chemical quantum mechanics together with transition state theory. Tunneling effect and internal rotations were also considered. The agreement between experimental and theoretical results for rate coefficients and KIE in an atmospherically relevant temperature range is discussed. However, both laboratory observations and computational predictions show no significant temperature dependence of the KIE for the ethane oxidation by OH radicals.
Predictive performance of rainfall thresholds for shallow landslides in Switzerland from gridded daily data
Authors: Leonarduzzi Elena , Molnar Peter , McArdell Brian W.
Published: July 2017

A high‐resolution gridded daily precipitation data set was combined with a landslide inventory containing over 2000 events in the period 1972–2012 to analyze rainfall thresholds which lead to landsliding in Switzerland. We colocated triggering rainfall to landslides, developed distributions of triggering and nontriggering rainfall event properties, and determined rainfall thresholds and intensity‐duration ID curves and validated their performance. The best predictive performance was obtained by the intensity‐duration ID threshold curve, followed by peak daily intensity Imax and mean event intensity Imean. Event duration by itself had very low predictive power. A single country‐wide threshold of Imax = 28 mm/d was extended into space by regionalization based on surface erodibility and local climate (mean daily precipitation). It was found that wetter local climate and lower erodibility led to significantly higher rainfall thresholds required to trigger landslides. However, we showed that the improvement in model performance due to regionalization was marginal and much lower than what can be achieved by having a high‐quality landslide database. Reference cases in which the landslide locations and timing were randomized and the landslide sample size was reduced showed the sensitivity of the Imax rainfall threshold model. Jack‐knife and cross‐validation experiments demonstrated that the model was robust. The results reported here highlight the potential of using rainfall ID threshold curves and rainfall threshold values for predicting the occurrence of landslides on a country or regional scale with possible applications in landslide warning systems, even with daily data.
Copper(I)‐Catalyzed Synthesis of 4,5‐Dihydropyrazolo[1,5‐a]pyrimidines via Cascade Transformation of N‐Propargylic Sulfonylhydrazones with Sulfonyl Azides
Authors: Ding Zong‐Cang , An Xiao‐Ming , Zeng Jia‐Hao , Tang Zhao‐Ning , Zhan Zhuang‐Ping
Published: July 2017

A rapid and effective approach to 4‐tosyl‐4,5‐dihydropyrazolo[1,5‐a]pyrimidines via copper‐catalyzed one‐pot cascade transformation of N‐propargylic sulfonylhydrazones with sulfonyl azides under mild conditions has been developed. This process relies on the copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) and intramolecular [4+2] cycloaddition of α,β‐unsaturated hydrazone with the in situ generated ketenimine intermediate, affording the useful bicyclization products with high efficiency.

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Individuals with sickle cell disease have a significantly greater vasoconstriction response to thermal pain than controls and have significant vasoconstriction in response to anticipation of pain
Authors: Khaleel Maha , Puliyel Mammen , Shah Payal , Sunwoo John , Kato Roberta M. , Chalacheva Patjanaporn , Thuptimdang Wanwara , Detterich Jon , Wood John C. , Tsao Jennie , Zeltzer Lonnie , Sposto Richard , Khoo Michael C. K. , Coates Thomas D.
Published: July 2017

The painful vaso‐occlusive crises (VOC) that characterize sickle cell disease (SCD) progress over hours from the asymptomatic steady‐state. SCD patients report that VOC can be triggered by stress, cold exposure, and, pain itself. We anticipated that pain could cause neural‐mediated vasoconstriction, decreasing regional blood flow and promoting entrapment of sickle cells in the microvasculature. Therefore, we measured microvascular blood flow in the fingers of both hands using plethysmography and laser‐Doppler flowmetry while applying a series of painful thermal stimuli on the right forearm in 23 SCD patients and 25 controls. Heat pain applied to one arm caused bilateral decrease in microvascular perfusion. The vasoconstriction response started before administration of the thermal pain stimulus in all subjects, suggesting that pain anticipation also causes significant vasoconstriction. The time delay between thermal pain application and global vasoconstriction ranged from 5 to 15.5 seconds and increased with age (P < .01). Although subjective measures, pain threshold and pain tolerance were not different between SCD subjects and controls, but the vaso‐reactivity index characterizing the microvascular blood flow response to painful stimuli was significantly higher in SCD patients (P = .0028). This global vasoconstriction increases microvascular transit time, and may promote entrapment of sickle cells in the microvasculature, making vaso‐occlusion more likely. The rapidity of the global vasoconstriction response indicates a neural origin that may play a part in the transition from steady‐state to VOC, and may also contribute to the variability in VOC frequency observed in SCD patients.
Fine Tuning of MOF‐505 Analogues To Reduce Low‐Pressure Methane Uptake and Enhance Methane Working Capacity
Authors: Zhang Mingxing , Zhou Wei , Pham Tony , Forrest Katherine A. , Liu Wenlong , He Yabing , Wu Hui , Yildirim Taner , Chen Banglin , Space Brian , Pan Yi , Zaworotko Michael J. , Bai Junfeng
Published: July 2017

We present a crystal engineering strategy to fine tune the pore chemistry and CH4‐storage performance of a family of isomorphic MOFs based upon PCN‐14. These MOFs exhibit similar pore size, pore surface, and surface area (around 3000 m2 g−1) and were prepared with the goal to enhance CH4 working capacity. [Cu2(L2)(H2O)2]n (NJU‐Bai 41: NJU‐Bai for Nanjing University Bai's group), [Cu2(L3)(H2O)2]n (NJU‐Bai 42), and [Cu2(L4)(DMF)2]n (NJU‐Bai 43) were prepared and we observed that the CH4 volumetric working capacity and volumetric uptake values are influenced by subtle changes in structure and chemistry. In particular, the CH4 working capacity of NJU‐Bai 43 reaches 198 cm3 (STP: 273.15 K, 1 atm) cm−3 at 298 K and 65 bar, which is amongst the highest reported for MOFs under these conditions and is much higher than the corresponding value for PCN‐14 (157 cm3 (STP) cm−3).
Colloidal Synthesis of Silicon–Carbon Composite Material for Lithium‐Ion Batteries
Authors: Su Haiping , Barragan Alejandro A. , Geng Linxiao , Long Donghui , Ling Licheng , Bozhilov Krassimir N. , Mangolini Lorenzo , Guo Juchen
Published: July 2017

We report colloidal routes to synthesize silicon@carbon composites for the first time. Surface‐functionalized Si nanoparticles (SiNPs) dissolved in styrene and hexadecane are used as the dispersed phase in oil‐in‐water emulsions, from which yolk–shell and dual‐shell hollow SiNPs@C composites are produced via polymerization and subsequent carbonization. As anode materials for Li‐ion batteries, the SiNPs@C composites demonstrate excellent cycling stability and rate performance, which is ascribed to the uniform distribution of SiNPs within the carbon hosts. The Li‐ion anodes composed of 46 wt % of dual‐shell SiNPs@C, 46 wt % of graphite, 5 wt % of acetylene black, and 3 wt % of carboxymethyl cellulose with an areal loading higher than 3 mg cm−2 achieve an overall specific capacity higher than 600 mAh g−1, which is an improvement of more than 100 % compared to the pure graphite anode. These new colloidal routes present a promising general method to produce viable Si–C composites for Li‐ion batteries.
Selective Palladium(II)‐Catalyzed Carbonylation of Methylene β‐C−H Bonds in Aliphatic Amines
Authors: Cabrera‐Pardo Jaime R. , Trowbridge Aaron , Nappi Manuel , Ozaki Kyohei , Gaunt Matthew J.
Published: July 2017

Palladium(II)‐catalyzed C−H carbonylation reactions of methylene C−H bonds in secondary aliphatic amines lead to the formation of trans‐disubstituted β‐lactams in excellent yields and selectivities. The generality of the C−H carbonylation process is aided by the action of xantphos‐based ligands and is important in securing good yields for the β‐lactam products.
Palladium‐Catalyzed Suzuki–Miyaura Cross‐Coupling of Secondary α‐(Trifluoromethyl)benzyl Tosylates
Authors: Brambilla Marta , Tredwell Matthew
Published: July 2017

A palladium‐catalyzed C(sp3)−C(sp2) Suzuki–Miyaura cross‐coupling of aryl boronic acids and α‐(trifluoromethyl)benzyl tosylates is reported. A readily available, air‐stable palladium catalyst was employed to access a wide range of functionalized 1,1‐diaryl‐2,2,2‐trifluoroethanes. Enantioenriched α‐(trifluoromethyl)benzyl tosylates were found to undergo cross‐coupling to give the corresponding enantioenriched cross‐coupled products with an overall inversion in configuration. The crucial role of the CF3 group in promoting this transformation is demonstrated by comparison with non‐fluorinated derivatives.
Drug transport in stimuli responsive acrylic and methacrylic interpenetrating polymer networks
Authors: Simeonov Marin , Monova Antonia , Kostova Bistra , Vassileva Elena
Published: July 2017

The interpenetrating polymer networks (IPNs) are recently gaining attention as sustained drug delivery systems because they could ensure a proper combination of functionality and network density to control the drug release profiles. This study aims to reveal how the functionality of two IPNs based on polyacrylamide and respectively poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) influences their smart behavior as well as their properties as delivery systems of the cationic drug verapamil hydrochloride (VPM). The “extra” α‐methyl group of PMAA results into a loss of the temperature sensitivity in the studied region and changes the pH responsivity of the PMAA/PAAM IPNs as compared to the PAA/PAAM IPNs. Moreover, the VPM diffusion in both IPNs depends on their composition due to the change in their functionality as well as of their network density. The “extra” α‐methyl group of PMAA defines its enhanced hydrophobicity and hence influences the VPM diffusion mechanism. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45380.
A statistical approach to evaluate the oxidative process of electrospun polyacrylonitrile ultrathin fibers
Authors: Santos de Oliveira Junior Mauro , Manzolli Rodrigues Bruno Vinícius , Marcuzzo Jossano Saldanha , Guerrini Lília Müller , Baldan Maurício Ribeiro , Rezende Mirabel Cerqueira
Published: July 2017

A systematic study using design of experiments was applied in order to map out the thermal stabilization of electrospun polyacrylonitrile mats and to investigate how oxidation and cyclization reactions are affected by rate, temperature, and time in an oxidative environment. Cyclization indexes were estimated by a simple methodology based on differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy data. Values of enthalpy and relative intensities of bands assigned to CN and CN bonds were used on calculation. The statistical planning applied in this study was important to show that not always longest treatment is effective to stabilize polyacrylonitrile, but also samples obtained in less than 3 h presented low values of exothermic peak on DSC, values of cyclization indexes near to 90%, both from DSC and Fourier transform infrared spectroscopy techniques, reduced weight loss in thermogravimetric analysis and O/C ratio higher than 10% by X‐ray photoelectron spectroscopy, that are appreciated characteristics to a precursor of high‐performance carbon materials. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45458.
Fluorine containing self‐crosslinking acrylic latexes with reduced flammability and their application as polymer binders for heterogeneous cation‐exchange membranes
Authors: Machotova Jana , Stranska Eliska , Skornok Jiri , Zarybnicka Lucie , Melanova Klara , Rychly Jozef , Ruckerova Adela
Published: July 2017

In this study, self‐crosslinking core–shell latexes comprising copolymerized perfluorethyl groups and a novel flame retardant based on phosphazene derivative were prepared by the semi‐continuous non‐seeded emulsion polymerization of 2,2,2‐trifluorethyl methacrylate, methyl methacrylate, butyl acrylate, methacrylic acid, and hexaallylamino‐cyclo‐triphosphazene as main monomers. For interfacial crosslinking, diacetone acrylamide was copolymerized into the shell layer of latex particles to provide sites for subsequent reaction with adipic acid dihydrazide. The heterogeneous cation‐exchange membranes were obtained by dispersing commercial strong acid cation‐exchange resin powder in the latex binder and casting the mixture followed by keto‐hydrazide crosslinking reaction. It was found that the increased concentration of fluorine atoms and phosphazene units in the macromolecular structure of interfacially crosslinked emulsion polymers resulted in a significant enhancement of their flame resistance and shape stability in aqueous environment. Moreover, the easily prepared heterogeneous cation‐exchange membranes based on latexes with higher amounts of fluorine and phosphazene units were shown to exhibit satisfactory physicochemical and electrochemical properties. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45467.
Opportunities and challenges of real‐time release testing in biopharmaceutical manufacturing
Authors: Jiang Mo , Severson Kristen A. , Love John Christopher , Madden Helena , Swann Patrick , Zang Li , Braatz Richard D.
Published: July 2017

Real‐time release testing (RTRT) is defined as “the ability to evaluate and ensure the quality of in‐process and/or final drug product based on process data, which typically includes a valid combination of measured material attributes and process controls” (ICH Q8[R2]). This article discusses sensors (process analytical technology, PAT) and control strategies that enable RTRT for the spectrum of critical quality attributes (CQAs) in biopharmaceutical manufacturing. Case studies from the small‐molecule and biologic pharmaceutical industry are described to demonstrate how RTRT can be facilitated by integrated manufacturing and multivariable control strategies to ensure the quality of products. RTRT can enable increased assurance of product safety, efficacy, and quality—with improved productivity including faster release and potentially decreased costs—all of which improve the value to patients. To implement a complete RTRT solution, biologic drug manufacturers need to consider the special attributes of their industry, particularly sterility and the measurement of viral and microbial contamination. Continued advances in on‐line and in‐line sensor technologies are key for the biopharmaceutical manufacturing industry to achieve the potential of RTRT.

Related article: http://onlinelibrary.wiley.com/doi/10.1002/bit.26378/full
Coupling the pretreatment and hydrolysis of lignocellulosic biomass by the expression of beta‐xylosidases
Authors: Martín Pérez Lucía , Benítez Casanova Laura , Moreno Pérez Antonio J. , Pérez Gómez Dolores , Gavaldá Martín Sandra , Ledesma‐García Laura , Valbuena Crespo Noelia , Díez García Bruno , Reyes‐Sosa Francisco M.
Published: July 2017

Thermochemical pretreatment and enzymatic hydrolysis are the areas contributing most to the operational costs of second generation ethanol in lignocellulosic biorefineries. The improvement of lignocellulosic enzyme cocktails has been significant in the recent years. Although the needs for the reduction of the energy intensity and chemical consumption in the pretreatment step are well known, the reduction of the severity of the process strongly affects the enzymatic hydrolysis yield. To explore the formulation requirements of the well known cellulolytic cocktail from Myceliophthora thermophila on mild pretreated raw materials, this cocktail was tested on steam exploded corn stover without acid impregnation. The low hemicellulose yield and significant accumulation of xylobiose compared with the standard pretreated material obtained with dilute acid impregnation evidenced a clear limitation in the conversion of xylan to xylose. In order to complement the beta‐xylosidase limitation, a selection of enzymes was expressed and tested in this fungus. A controlled expression of xylosidases from Aspergillus nidulans, Aspergillus fumigatus, and Fusarium oxysporum allowed recovering hemicellulose yields reached with standard acid treated material. The results underline the need of parallel development of the pretreatment process with the optimization of the formulation of the enzymatic cocktails.
Mechanisms of breast cancer risk in shift workers: association of telomere shortening with the duration and intensity of night work
Authors: Samulin Erdem Johanna , Notø Heidi Ødegaard , Skare Øivind , Lie Jenny‐Anne S. , Petersen‐Øverleir Marte , Reszka Edyta , Pepłońska Beata , Zienolddiny Shanbeh
Published: July 2017

Occupational factors such as shiftwork and especially night work that involves disruption of the circadian rhythm may contribute to increased breast cancer risk. Circadian disruption may also affect telomere length (TL). While short TL generally is associated with increased cancer risk, its association with breast cancer risk is inconclusive. We suggest that working schedules might be an important factor in assessment of effects of TL on breast cancer risk. Moreover, telomere shortening might be a potential mechanism for night work‐related breast cancer. In this study, effects of shift work on TL and its association with breast cancer risk were investigated in a nested breast cancer case–control study of Norwegian nurses. TL was assessed by qPCR in DNA from 563 breast cancer patients and 619 controls. Here, we demonstrate that TL is affected by intensive night work schedules, as work with six consecutive night for a period of more than 5 years was associated with decreased telomere lengths (−3.18, 95% CI: −6.46 to −0.58, P = 0.016). Furthermore, telomere shortening is associated with increased breast cancer risk in workers with long periods of consecutive night shifts. Thus, nurses with longer telomere lengths had a lower risk for breast cancer if they had worked more than four (OR: 0.37, 95% CI: 0.16–0.79, P = 0.014) or five (OR: 0.31, 95% CI: 0.10–0.83, P = 0.029) consecutive night shifts for a period of 5 years or more. These data suggest that telomere shortening is associated with the duration and intensity of night work and may be a contributing factor for breast cancer risk among female shift workers.
Hormone factors play a favorable role in female head and neck cancer risk
Authors: Hashim Dana , Sartori Samantha , Vecchia Carlo La , Serraino Diego , Maso Luigino Dal , Negri Eva , Smith Elaine , Levi Fabio , Boccia Stefania , Cadoni Gabriella , Luu Hung N. , Lee Yuan‐Chin Amy , Hashibe Mia , Boffetta Paolo
Published: July 2017

Due to lower female incidence, estimates of exogenous and endogenous hormonal factors in head and neck cancers (HNCs, comprising cancers of the oral cavity, oropharynx, hypopharynx, and larynx) among women have been inconsistent and unable to account for key HNC risk factors. We pooled data from 11 studies from Europe, North America, and Japan. Analysis included 1572 HNC female cases and 4343 controls. Pooled odds ratios (ORs) estimates and their 95% confidence intervals (CIs) were calculated using multivariate logistic regression models adjusting for tobacco smoking and alcohol drinking. Lower risk was observed in women who used hormone replacement therapy (HRT) (OR = 0.58; 95% CI: 0.34–0.77). Pregnancy (OR = 0.61; 95% CI: 0.42–0.90) and giving birth (OR = 0.59; 95% CI: 0.38–0.90) at <35 years of age were inversely associated with HNCs. An inverse association with HNC was observed with age at start of HRT use (OR = 0.59; 95% CI: 0.39–0.90) for each additional 10 years and with duration of use (OR = 0.87; 95% CI: 0.76–0.99 for every 3 years). Exogenous female hormone use is associated with a nearly twofold risk reduction in female HNCs. The lower female HNC incidence may, in part, be explained by endogenous and exogenous estrogen exposures.
Hsa_circ_0020397 regulates colorectal cancer cell viability, apoptosis and invasion by promoting the expression of the miR‐138 targets TERT and PD‐L1
Authors: Zhang Xiu‐li , Xu Ling‐ling , Wang Fang
Published: July 2017

Colorectal cancer (CRC) is a common human gastrointestinal cancer, and recent studies indicate that circular RNA (circRNA) may regulate cancer development. In this study, we assess the role of circRNA specifically in colorectal cancer. Our quantitative PCR assays demonstrate an upregulation of the circRNA has_circ_0020397 and a downregulation of miR‐138 in CRC cells, as well as a negative correlation between these two. Using a dual‐luciferase reporter assay, we show evidence of miR‐138‐binding sites on hsa_circ_0020397, and that overexpression of hsa_circ_0020397 could inhibit the downregulation of luciferase activity by miR‐138. Although hsa_circ_0020397 did not influence miR‐138 expression per se, has_circ_0020397 did inhibit miR‐138 activity, as examined via the expression of miR‐138 targets telomerase reverse transcriptase (TERT) and programmed death‐ligand 1 (PD‐L1). Control treatments with plasmids overexpressing linear hsa_circ_0020397 did not have these effects. Hsa_circ_0020397 promoted cell viability and invasion of CRC cells and inhibited their apoptosis, whereas miR‐138 had the opposite effect. Nevertheless, hsa_circ_0020397 antagonized miR‐138 suppression of cell growth. When TERT or PD‐L1 expression was suppressed with siRNAs, the above functions of hsa_circ_0020397 were attenuated, suggesting that hsa_circ_0020397 can regulate CRC cell viability, apoptosis and invasion by promoting the expression of miR‐138 target genes. These findings support the role of circRNA in CRC pathogenesis.
Individualizing dual antiplatelet therapy duration: Prediction tools, genomics, and clinical judgment
Authors: Chatterjee Arka , Hillegass William B.
Published: July 2017

Key Points

Prolonged dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) on average reduces the risk of subsequent myocardial infarction (MI) but increases major bleeds.

Individualizing duration of DAPT based on the DAPT trial's net benefit prediction tool would likely optimize outcome beyond population average recommendations. Individualizing agent selection and duration of therapy based on genomic data may further improve outcomes.

Clinical judgment remains the most important tool to tailor DAPT duration based on a large array of additional relevant factors not captured by predition rules or genomics.
Paravalvular leak versus need for permanent pacemaker after TAVR: Sailing between Scylla and Charybdis
Authors: Cilingiroglu Mehmet , Marmagkiolis Konstantinos
Published: July 2017

Key Points

Absence or minimization of PVL after TAVR and its potential association with higher rates of PPM placement has been the Achilles’ heel of TAVR procedures.

Pre‐existing RBBB and depth of implantation are independent predictors of PPM need after Lotus valve implantation.

Optimization of device design, increased operator experience, and focus on accurate device placement seem to result in decreased need for PPM after Lotus valve implantation.
Sleep deprivation in interventional cardiology: Implications for patient care and physician‐health
Authors: Sandoval Yader , Lobo Angie S. , Somers Virend K. , Rosenfield Kenneth , Bradley Steven M. , Sorajja Paul , Tajti Peter , Brilakis Emmanouil S.
Published: July 2017

The burden and impact of sleep deprivation on both patient care and on the health of interventional cardiologists is not well understood. Due to the nature of emergent procedures occurring in the cardiac catheterization laboratory, interventionalists are prone to suffer from acute and/or chronic sleep deprivation. Sleep deprivation has been associated with numerous adverse effects, such as impaired performance, cognitive deficits, reduced psychomotor vigilance, and workplace errors and injuries, among many others. Although sleep deprivation has been linked to more errors in trainees, there is paucity of data addressing outcomes in interventional cardiology. The purpose of this overview is to explore the possible impact of sleep deprivation on interventional cardiology in relation to patient care and physician health, and examine potential approaches to this issue.
Managing bisphosphonate‐related osteonecrosis of the jaws with xenografts: a case report
Authors: de Oliveira Ruellas Aluísio Martins , Peruzzo Daiane Cristina , Napimoga Marcelo Henrique
Published: July 2017

Key Clinical Message

It is possible to manage large bone destruction induced by BRONJ using xenograft grafting to promote a bone formation.
Repeated successful use of eltrombopag in chronic primary immune thrombocytopenia: description of an intriguing case
Authors: Santoro Cristina , Volpicelli Paola , Baldacci Erminia , Ferrara Grazia , Di Rocco Alice , Ferretti Antonietta , Porrazzo Marika , Mazzucconi Maria Gabriella
Published: July 2017

Key Clinical Message

Thrombopoietin receptor agonists (TPO‐RAs) are used as effective alternative treatments in ITP patients unresponsive to first‐/second‐line therapies. TPO‐RAs can also be used to normalize platelet count to safely perform invasive procedures and chemotherapy, in case of malignancies. In few responsive patients, TPO‐RAs can be suspended maintaining a sustained response.
Theoretical Explanation of the Photogenerated Carrier Separation at the Surface Junction
Authors: Song Weiyu , Ma Sicong , Wang Lu , Liu Jian , Zhao Zhen
Published: July 2017

For photocatalytic reactions, the fabrication of surface junction has been proven to be an effective method to increase the photogenerated carrier (excited electrons and photogenerated holes) separation efficiency. However, the carrier separation mechanism has not been studied in detail. In this work, density functional theory has been employed to study the photogenerated carrier‐separation mechanism based on an interfacial model consisting of TiO2 (1 0 1) and (0 0 1) facets. Both excited electrons and photogenerated holes preferentially locate on the (0 0 1) facets rather than the (1 0 1) facets. However, the high conduction‐band energy level of the interface inhibits the electron interfacial migration. In contrast to the exited‐electrons migration process, the suitable valence‐band energy of interface permits the hole interfacial migration from the (1 0 1) to the (0 0 1) facets. The electrons easily recombine with the holes on the (0 0 1) facets owing to the holes overflow effect. Excited electrons and holes would fill the (1 0 1) facets and (0 0 1) facets, respectively. Based on such interfacial energy band properties, we propose a new photocatalytic material design concept, named “selective migration” structure, which can promote the photogenerated carrier separation and offer more strongly reductive electrons for the photoreduction reaction or more strongly oxidative holes for the photooxidation reaction. These results are expected to provide a deeper understanding of the surface junction and a guide for designing new photocatalysts.
Functionalities tuned enantioselectivity of phenylcarbamate cyclodextrin clicked chiral stationary phases in HPLC
Authors: Tang Jian , Lin Yuzhou , Yang Bo , Zhou Jie , Tang Weihua
Published: July 2017

The mixed chloro‐ and methyl‐ functionalities can greatly modulate the enantioselectivities of phenylcarbamate cyclodextrin (CD) clicked chiral stationary phases (CSPs). A comparison study is herein reported for per(4‐chloro‐3‐methyl)phenylcarbamate and per(2‐chloro‐5‐methyl)phenylcarbamate β‐CD clicked CSPs (i.e., CCC4M3‐CSP and CCC2M5‐CSP). The enantioselectivity dependence on column temperature was studied in both normal‐phase and reversed‐phase mode high performance liquid chromatography (HPLC). The thermodynamic study revealed that the stronger intermolecular interactions can be formed between CCC4M3‐CSP and chiral solutes to drive the chiral separation. The higher enantioselectivities of CCC4M3‐CSP were further demonstrated with the enantioseparation of 17 model racemates in HPLC.