bluuebunny/crossref_metadata_2025 huggingface dataset:
The cell on the edge of life and death: Crosstalk between autophagy and apoptosis
Authors: Kasprowska-Liśkiewicz Daniela
Published: September 2017

Recently, the crosstalk between autophagy and apoptosis has attracted broader attention. Basal autophagy serves to maintain cell homeostasis, while the upregulation of this process is an element of stress response that enables the cell to survive under adverse conditions. Autophagy may also determine the fate of the cell through its interactions with cell death pathways. The protein networks that control the initiation and the execution phase of these two processes are highly interconnected. Several scenarios for the crosstalk between autophagy and apoptosis exist. In most cases, the activation of autophagy represents an attempt of the cell to cope with stress, and protects the cell from apoptosis or delays its initiation. Generally, the simultaneous activation of pro-survival and pro-death pathways is prevented by the mutual inhibitory crosstalk between autophagy and apoptosis. But in some circumstances, autophagy or the proteins of the core autophagic machinery may promote cellular demise through excessive self-digestion (so-called “autophagic cell death”) or by stimulating
the activation of other cell death pathways. It is controversial whether cells actually die via
autophagy, which is why the term “autophagic cell death” has been under intense debate lately.
This review summarizes the recent findings on the multilevel crosstalk between autophagy
and apoptosis in aspects of common regulators, mutual inhibition of these processes, the stimulation
of apoptosis by autophagy or autophagic proteins and finally the role of autophagy
as a death-execution mechanism.
Influence of vitamin D in bone healing
Authors: Freitas Rafaela Pignatti de , Nunes Fernanda Parini , Santos Livia Marcela dos , Weckwerth Paulo Henrique , Silveira Elcia Maria Varize , Gulinelli Jéssica Lemos , Santos Pamela Leticia
Published: September 2017

Introduction: Vitamin D is an hormone whose function is to maintain calcium and phosphorus homeostasis in order to ensure bone mineralization. Vitamin-D deficiency can lead to severe diseases, including an atypical mineralization of bone, because it decreases osteoblasts activity. It has become increasingly common and it has been mainly observed in obese people who avoid direct sunlight exposure to their skin and have a vitamin D-deficient diet. Objectives: Due to the high incidence of hypovitaminosis D in the world population, this study sought to provide an analytical and minute literature review associating vitamin D deficiency with bone healing. Methods: To accomplish this, a bibliographic research was conducted in the following database: Medline (PubMed), Science Direct, Scielo, Periódicos CAPES (Brazilian database), and Bireme (Latin-American database). Results: From the main longitudinal and meta-analytic studies, as well as the main studies conducted on animals, published between 1995 and 2015, 20 articles were selected according to the inclusion criteria. Conclusion: From this review, it was concluded that vitamin D influences the cellular process of bone healing and that the exact mechanism of this influence is still unclear.
Management of a Dentigerous Cyst in a Child with Robin Sequence
Authors: Mirhaidari Shayda , Murthy Ananth
Published: September 2017

This is a brief clinical report describing an 18-month-old female with Robin sequence found to have an incidental mandibular cystic lesion on a head computed tomography scan in the preoperative workup before performing mandibular distraction. She underwent enucleation of the tumor, which was found to be a dentigerous cyst. One year following cyst enucleation, mandibular distraction was performed in order to alleviate her tongue-based obstruction. This case demonstrates the ability of the mandibular bone to successfully regenerate after undergoing cyst enucleation.
Le droit de l’eau face aux déluges bibliques et aux sécheresses millénaires : la gestion des conflits d’usages causés par la variabilité hydrologique
Authors: Tremblay Hugo
Published: September 2017

La variabilité hydrologique impose les contraintes les plus importantes relativement à la gestion des ressources hydriques. Elle suppose que le volume d’eau disponible en un lieu donné varie constamment, souvent de façon imprévisible, ce qui oblige à composer avec des incertitudes importantes. Le réchauffement planétaire augmente les variations climatiques, de même que les évènements météorologiques extrêmes, ce qui multiplie les incertitudes liées aux projections hydrologiques. Les caractéristiques de la variabilité hydrologique induisent une problématique particulièrement aiguë pour le droit qui constitue un ensemble de règles générales capables de guider et d’encadrer de façon prévisible, stable et sécuritaire la conduite des personnes. Cet article étudie la façon dont le droit gère les conflits d’usages de l’eau qui se manifestent dans un contexte de fluctuations des régimes hydriques. L’exercice permet de mettre en évidence certaines contraintes inhérentes que le droit impose à la gestion des ressources hydriques et à l’adaptation aux changements climatiques.
La computation des délais prévus par le Code du travail
Authors: Desjardins Marie-Claude , Makela Finn
Published: September 2017

L’objectivation du temps est importante pour plusieurs domaines de droit, et cela est particulièrement vrai pour le droit du travail. Dans le domaine du droit des rapports collectifs du travail notamment, la question précise des délais et de leur computation joue un rôle crucial, à tout le moins en Amérique du Nord, où la législation, inspirée de la Wagner Act, impose des limites importantes, du point de vue du temps, à l’exercice des droits qu’elle confère. Ces restrictions temporelles ne sont pas que de mécanismes procéduraux nécessaires à la mise en oeuvre du système : elles en sont plutôt des éléments substantiels.

Les acteurs du monde du travail sont aux prises quotidiennement avec les délais prévus dans le Code du travail du Québec. En effet, ce dernier prévoit des moments précis pour l’acquisition, l’exercice et l’extinction des droits des employeurs, des syndicats et des salariés. Les règles relatives à la computation des délais sont complexes et font fréquemment l’objet de controverses jurisprudentielles. Or, jusqu’à présent, la doctrine s’est peu intéressée à la computation des délais en droit du travail québécois, malgré son importance. L’article qui suit constitue une étude exhaustive des fondements des règles de computation des délais et de leur mise en oeuvre dans le contexte du Code du travail. La première partie permet d’exposer les sources des règles applicables à la computation des délais et les concepts clés qui facilitent leur mise en oeuvre. La seconde partie s’intéresse à l’application de ces règles à des situations concrètes, en particulier dans le contexte de l’accréditation, de l’acquisition du droit de grève ou de lock-out et de recours fondés sur le Code du travail ou sur une convention collective.
Le traitement judiciaire de la preuve scientifique : une modélisation des attitudes du juge face à la connaissance scientifique en droit de la responsabilité civile
Authors: Vergès Etienne , Khoury Lara
Published: September 2017

Le traitement judiciaire de la preuve scientifique en droit de la responsabilité civile en présence d’incertitude ou de débats est un sujet qui fait couler de plus en plus d’encre. Dans leur étude de droit comparé qui porte sur des jugements au fond de la France et du Québec, les auteurs évaluent la façon dont le juge accède à la conviction qu’un fait est prouvé lorsque cette représentation intellectuelle passe par la médiation de la connaissance scientifique, c’est-à-dire qu’elle nécessite d’avoir recours à une analyse scientifique de la situation de fait. L’étude s’interroge donc sur la manière dont les juges français et québécois appréhendent cette connaissance scientifique et se focalise ainsi sur le rapport des juges à la connaissance scientifique. En se penchant sur le raisonnement judiciaire français et québécois en matière de responsabilité civile, l’étude permet d’évaluer ce rapport au sein d’un champ de droit dont les racines sont similaires dans les deux ressorts, à la lumière toutefois d’une structure judiciaire et d’un droit de la preuve distincts.
A quantitative hypermorphic CNGC allele confers ectopic calcium flux and impairs cellular development
Authors: Chiasson David M , Haage Kristina , Sollweck Katharina , Brachmann Andreas , Dietrich Petra , Parniske Martin
Published: September 2017

The coordinated control of Ca2+ signaling is essential for development in eukaryotes. Cyclic nucleotide-gated channel (CNGC) family members mediate Ca2+ influx from cellular stores in plants (Charpentier et al., 2016; Gao et al., 2016; Frietsch et al., 2007; Urquhart et al., 2007). Here, we report the unusual genetic behavior of a quantitative gain-of-function CNGC mutation (brush) in Lotus japonicus resulting in a leaky tetrameric channel. brush resides in a cluster of redundant CNGCs encoding subunits which resemble metazoan voltage-gated potassium (Kv1-Kv4) channels in assembly and gating properties. The recessive mongenic brush mutation impaired root development and infection by nitrogen-fixing rhizobia. The brush allele exhibited quantitative behavior since overexpression of the cluster subunits was required to suppress the brush phenotype. The results reveal a mechanism by which quantitative competition between channel subunits for tetramer assembly can impact the phenotype of the mutation carrier.
Structural inhibition of dynamin-mediated membrane fission by endophilin
Authors: Hohendahl Annika , Talledge Nathaniel , Galli Valentina , Shen Peter S , Humbert Frédéric , De Camilli Pietro , Frost Adam , Roux Aurélien
Published: September 2017

Dynamin, which mediates membrane fission during endocytosis, binds endophilin and other members of the Bin-Amphiphysin-Rvs (BAR) protein family. How endophilin influences endocytic membrane fission is still unclear. Here, we show that dynamin-mediated membrane fission is potently inhibited in vitro when an excess of endophilin co-assembles with dynamin around membrane tubules. We further show by electron microscopy that endophilin intercalates between turns of the dynamin helix and impairs fission by preventing trans interactions between dynamin rungs that are thought to play critical roles in membrane constriction. In living cells, overexpression of endophilin delayed both fission and transferrin uptake. Together, our observations suggest that while endophilin helps shape endocytic tubules and recruit dynamin to endocytic sites, it can also block membrane fission when present in excess by inhibiting inter-dynamin interactions. The sequence of recruitment and the relative stoichiometry of the two proteins may be critical to regulated endocytic fission.
MazF activation promotes translational heterogeneity of thegrcAmRNA inEscherichia colipopulations
Authors: Nikolic Nela , Didara Zrinka , Moll Isabella
Published: September 2017

Bacteria adapt to adverse environmental conditions by altering gene expression patterns. Recently, a novel stress adaptation mechanism has been described that allowsEscherichia colito alter gene expression at the post-transcriptional level. The key player in this regulatory pathway is the endoribonuclease MazF, the toxin component of the toxin-antitoxin modulemazEFthat is triggered by various stressful conditions. In general, MazF degrades the majority of transcripts by cleaving at ACA sites, which results in the retardation of bacterial growth. Furthermore, MazF can process a small subset of mRNAs and render them leaderless by removing their ribosome binding site. MazF concomitantly modifies ribosomes, making them selective for the translation of leaderless mRNAs. In this study, we employed fluorescent reporter-systems to investigatemazEFexpression during stressful conditions, and to infer consequences of the mRNA processing mediated by MazF on gene expression at the single-cell level. Our results suggest thatmazEFtranscription is maintained at low levels in single cells encountering adverse conditions, such as antibiotic stress or amino acid starvation. Moreover, using thegrcAmRNA as a model for MazF-mediated mRNA processing, we found that MazF activation promotes heterogeneity in thegrcAreporter expression, resulting in a subpopulation of cells with increased levels of GrcA reporter protein.
The evolutionary history of Stomatopoda (Crustacea: Malacostraca) inferred from molecular data
Authors: Van Der Wal Cara , Ahyong Shane T. , Ho Simon Y.W. , Lo Nathan
Published: September 2017

The crustacean order Stomatopoda comprises seven superfamilies of mantis shrimps, found in coastal waters of the tropics and subtropics. These marine carnivores bear notable raptorial appendages for smashing or spearing prey. We investigated the evolutionary relationships among stomatopods using phylogenetic analyses of three mitochondrial and two nuclear markers. Our analyses recovered the superfamily Gonodactyloidea as polyphyletic, withHemisquillaas the sister group to all other extant stomatopods. A relaxed molecular clock, calibrated by seven fossil-based age constraints, was used to date the origin and major diversification events of stomatopods. Our estimates suggest that crown-group stomatopods (Unipeltata) diverged from their closest crustacean relatives about 340 Ma (95% CRI [401–313 Ma]). We found that the specialized smashing appendage arose after the spearing appendage ∼126 Ma (95% CRI [174–87 Ma]). Ancestral state reconstructions revealed that the most recent common ancestor of extant stomatopods had eyes with six midband rows of hexagonal ommatidia. Hexagonal ommatidia are interpreted as plesiomorphic in stomatopods, and this is consistent with the malacostracan ground-plan. Our study provides insight into the evolutionary timescale and systematics of Stomatopoda, although further work is required to resolve with confidence the phylogenetic relationships among its superfamilies.
Hydrothermal Venting at Hinepuia Submarine Volcano, Kermadec Arc: Understanding Magmatic‐Hydrothermal Fluid Chemistry
Authors: Stucker Valerie K. , Walker Sharon L. , de Ronde Cornel E. J. , Caratori Tontini Fabio , Tsuchida Shinji
Published: September 2017

The Hinepuia volcanic center is made up of two distinct edifices aligned northwest to southeast, with an active cone complex in the SE. Hinepuia is one of several active volcanoes in the northern segment of the Kermadec arc. Regional magnetic data show no evidence for large‐scale hydrothermal alteration at Hinepuia, yet plume data confirm present‐day hydrothermal discharge, suggesting that the hydrothermal system may be too young to have altered the host rocks with respect to measurable changes in magnetic signal. Gravity data are consistent with crustal thinning and shallow mantle under the volcanic center. Following the discovery of hydrothermal plumes over Hinepuia, the submersible Shinkai 6500 was used to explore the SE cone and sample hydrothermal fluids. The chemistry of hydrothermal fluids from submarine arc and backarc volcanoes is typically dominated by water‐rock interactions and/or magmatic degassing. Chemical analyses of vent fluids show that Hinepuia does not quite fit either traditional model. Moreover, the Hinepuia samples fall between those typically ascribed to both end‐member fluid types when plotted on a K‐Mg‐SO4 ternary diagram. Due to evidence of strong degassing, abundant native sulfur deposition, and H2S presence, the vent sampled at Hinepuia is ultimately classified as a magmatic‐hydrothermal system with a water‐rock influence. This vent is releasing water vapor and magmatic volatiles with a notable lack of salinity due to subcritical boiling and phase separation. Magmatic‐hydrothermal fluid chemistry appears to be controlled by a combination of gas flux, phase separation processes, and volcano evolution and/or distance from the magma source.
The Impacts of Seawater Mg/Ca and Temperature on Element Incorporation in Benthic Foraminiferal Calcite
Authors: de Nooijer L. J. , van Dijk I. , Toyofuku T. , Reichart G. J.
Published: September 2017

On geological timescales, oceanic [Mg2+] and [Ca2+] vary with changing rates of weathering, seafloor spreading and dolomite formation. Accurate reconstruction of the ratio between [Mg2+] and [Ca2+] in seawater (Mg/Casw), may potentially be reconstructed using foraminiferal Mg/Ca ratios. Since both temperature and seawater Mg/Ca impact foraminiferal Mg/Ca, successful reconstruction of Mg/Casw requires quantification of both these parameters independently on foraminiferal Mg/Ca, as well as their combined effect on Mg‐incorporation. Here we present the combined and isolated impacts of temperature and Mg/Casw on Mg incorporation in two model species, the benthic hyaline (i.e., perforate) foraminifer Elphidium crispum and porcelaneous (i.e., miliolid) foraminifer Quinqueloculina sp. using controlled growth experiments. Specimens of these two species were kept at four different temperatures (ranging from 10 to 27°C) and three Mg/Casw's (3.4, 6.4 and 8.5 mol/mol), resulting in 12 experimental conditions. Newly grown calcite was analyzed for a number of elements (Na, Mg and Sr) by laser ablation‐ICP‐MS. Results show that although the Mg/Ca varied by more than an order of magnitude between species, the sensitivity of Mg incorporation with respect to temperature appeared not to be influenced by Mg/Casw. By extension, these results may also help improving accuracy in the reconstruction of past Mg/Casw based on foraminifera with contrasting Mg/Ca.
A Possible Causative Mechanism of Raton Basin, New Mexico and Colorado Earthquakes Using Recent Seismicity Patterns and Pore Pressure Modeling
Authors: Nakai J. S. , Weingarten M. , Sheehan A. F. , Bilek S. L. , Ge S.
Published: September 2017

The Raton Basin had the highest number of earthquakes in Colorado and New Mexico from 2008 to 2010. The rate of both wastewater injection and earthquakes in the basin increased dramatically starting in 1999 and 2001, respectively. We compare seismicity (ML0.0–4.3) in the Raton Basin from 2008 to 2010 with the location of modeled pore pressure increases, estimated from cumulative wastewater injection volume beginning at the onset of well injection to present for all 28 injection wells in the basin. We find that modeled pore pressures in the New Mexico portion of the basin (above 0.08 MPa) reached that necessary to induce seismicity (0.01–0.1 MPa). We simulate a fault plane, 20 km long, inferred from seismicity in Vermejo Park (1355 of 1881 total earthquakes), in our model. We find that the relatively permeable fault allows pressures to migrate deeper into the basin at the onset of our study in 2008, providing an explanation for the observed seismicity in the basement. The Tercio lineament of earthquakes is similar to Vermejo Park fault in strike, but has fewer earthquakes (129) and is shorter in length (9 km). Seismicity in Vermejo Park occurs continuously, but earthquakes occur episodically in the remainder of the basin. The number of earthquakes we observe in seven seismic clusters increases as the cumulative injected volume from wells within 5 km increases. The modeled pore pressures, earthquake locations, and relationship between cumulative volume and number of earthquakes indicate that seismicity in the Raton Basin is likely induced.
An Assessment of Drift Correction Alternatives for CMIP5 Decadal Predictions
Authors: Choudhury Dipayan , Sen Gupta Alexander , Sharma Ashish , Mehrotra Rajeshwar , Sivakumar Bellie
Published: September 2017

Drift correction is an important step before using the outputs of decadal prediction experiments and has seen considerable research. However, most drift correction studies consider a relatively small sample of variables and models. Here, we present a systematic application of the existing drift correction strategies for decadal predictions of various sea surface temperature‐based metrics from a suite of five state‐of‐the‐art climate models (CanCM4i1, GFDL‐CM2.1, HadCM3i2&i3, MIROC5, and MPI‐ESM‐LR). The best method of drift correction for each metric and model is reported. Preliminary analysis suggests that there is no single method of drift correction that consistently performs best. Initial condition‐based drift correction provides the lowest errors in most regions for MIROC5 and the two HadCM3 models, whereas the trend‐based drift correction produces lowest errors for CanCM4i1, GFDL‐CM2.1, and MPI‐ESM‐LR over the largest share of the area. There is no merit in using a k‐nearest neighbor approach for these drift correction methods. Further, in almost all cases, the multimodel ensemble outperforms the individual models, and thus, the study conclusively suggests using forecasts based on multimodel averages. We also show some additional benefit to be gained by drift correcting each model/metric using their best correction method prior to model averaging and suggest that the results presented here would help potential users expend time and resources judiciously while dealing with outputs from these experiments.
Impact of Lateral Mixing in the Ocean on El Nino in a Suite of Fully Coupled Climate Models
Authors: Gnanadesikan Anand , Russell Alexandria , Pradal Marie‐Aude , Abernathey Ryan
Published: September 2017

We examine the dependence of the amplitude of the El Nino‐Southern Oscillation (ENSO) on the mixing coefficient parameterizing the lateral mixing of tracers (ARedi) The value of this coefficient is very uncertain, ranging in Earth System Models between a few hundred and a few thousand m2 s−1, with some observational estimates showing even higher values. A suite of simulations is made with two spatially varying distributions of ARedi derived from satellite observations as well as four simulations where a spatially constant ARedi is varied over a factor of 6. Surprisingly, larger values of ARedi result in stronger ENSO variability despite the higher mixing coefficients producing more efficient lateral diffusive damping of anomalies. This is because lateral mixing also warms the cold tongue, increasing vertical temperature gradients and decreasing horizontal temperature gradients. Larger vertical temperature gradients make sea surface temperatures more responsive to atmospheric forcing, while smaller horizontal temperature gradients shift the location of convection and make the atmosphere more responsive to sea surface temperature anomalies. The last effect holds across simulations as well as within individual simulations and thus also helps to explain interdecadal variability in ENSO amplitude. By contrast, a previously proposed anticorrelation between the amplitude interannual and annual variability does not hold across simulations, although it does hold within simulations. The propagation of thermocline depth anomalies is relatively insensitive to the value of ARedi. Properly specifying the lateral mixing along the equator (including distinguishing the impacts of subgridscale turbulence and tropical instability waves) appears essential to simulating ENSO.
Timing and Impact of Decisions to Adjust Disease‐Modifying Antirheumatic Drug Therapy for Rheumatoid Arthritis Patients With Active Disease
Authors: Shaw Yomei , Chang Chung‐Chou H. , Levesque Marc C. , Donohue Julie M. , Michaud Kaleb , Roberts Mark S.
Published: September 2017

Objective

Guidelines recommend that rheumatoid arthritis (RA) patients with moderate‐to‐high disease activity (MHDAS) adjust disease‐modifying antirheumatic drug (DMARD) therapy at least every 3 months until reaching low disease activity or remission (LDAS). We examined how quickly RA patients with MHDAS adjust DMARD therapy in clinical practice, and whether those who adjust DMARDs within 90 days in response to MHDAS reach LDAS sooner.

Methods

We identified RA patients with MHDAS in the University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research registry, and conducted a competing risks regression on time to DMARD therapy adjustment and a Cox regression on time to LDAS.

Results

We identified 538 eligible subjects with 943.5 patient‐years of followup. Sixty percent of patients with persistent MHDAS adjusted DMARDs within 90 days. Among all subjects, median times to DMARD adjustment and LDAS were 154 (interquartile range [IQR] 1–706) days and 301 (IQR 140–706) days, respectively. Being elderly (subdistribution hazard ratio [SHR] 0.61, P = 0.02), lower baseline disease activity (SHR 0.72, P < 0.01), longer duration of RA (SHR 0.98, P < 0.01), and biologic use (SHR 0.71, P < 0.01) were significantly associated with longer times to therapy adjustment. African American race (hazard ratio [HR] 0.63, P = 0.01), higher baseline disease activity (HR 0.75, P < 0.01), and not adjusting DMARD therapy within 90 days (HR 0.76, P = 0.01) were associated with longer times to LDAS.

Conclusion

Adjusting DMARDs within 90 days was associated with shorter times to LDAS, but many patients with persistent MHDAS waited >90 days to adjust DMARDs. Interventions are needed to address the timeliness of DMARD adjustments for RA patients with MHDAS.
Trajectories of Fear‐Avoidance Beliefs on Physical Activity Over Two Years in People With Rheumatoid Arthritis
Authors: Demmelmaier Ingrid , Björk Annika , Dufour Alyssa B. , Nordgren Birgitta , Opava Christina H.
Published: September 2017

Objective

To identify and describe 2‐year trajectories of fear‐avoidance beliefs on physical activity and to identify predictors of these trajectories in people with rheumatoid arthritis (RA).

Methods

We included 2,569 persons with RA (77% women, mean age 58 years). Data on fear‐avoidance beliefs (Fear‐Avoidance Beliefs Questionnaire physical activity subscale [FABQ‐PA]; range 0–24), sociodemographics, disease‐related variables, self‐efficacy, and health‐enhancing physical activity (HEPA) were collected from registers and by questionnaires at baseline, 14, and 26 months. K‐means cluster analysis was used to identify fear‐avoidance trajectories, and multinomial logistic regression was used to identify predictors of trajectory membership.

Results

Three trajectories of fear‐avoidance beliefs were identified: low (n = 1,060, mean FABQ‐PA = 3), moderate (n = 1,043, mean FABQ‐PA = 9), and high (n = 466, mean FABQ‐PA = 15). Consistent predictors of being in the high fear‐avoidance trajectory versus the other 2 trajectories were high activity limitation, male sex, income below average, not performing current HEPA, and elevated anxiety/depression. In addition, less consistent predictors such as shorter education, more pain, and low exercise self‐efficacy were also identified.

Conclusion

Stable trajectories of fear‐avoidance beliefs on physical activity exist among people with RA. Fear‐avoidance may be targeted more effectively by tailoring physical activity promotion to vulnerable socioeconomic groups, men, and those with high activity limitation and anxiety/depression.
Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program
Authors: Mariette Xavier , Chen Connie , Biswas Pinaki , Kwok Kenneth , Boy Mary G.
Published: September 2017

Objective

Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). We characterized lymphoma events in the tofacitinib RA clinical development program.

Methods

Lymphoma events (up to March 2015) were identified from 19 tofacitinib studies (2 phase I, 9 phase II, 6 phase III, and 2 long‐term extension) of patients with moderate to severe RA. Patients in these studies received tofacitinib dosed at 1–30 mg twice daily or 20 mg once daily, as monotherapy or with conventional synthetic disease‐modifying antirheumatic drugs. Lymphoma incidence rates (IRs; number of patients with events/100 patient‐years) and standardized incidence ratios (SIRs) were calculated. A descriptive case–matched control analysis (1:4) was performed to identify potential risk factors for lymphoma.

Results

A total of 6,194 patients received tofacitinib (19,406 patient‐years of exposure, 3.4 years median treatment duration). Nineteen lymphomas occurred (IR 0.10 [95% confidence interval (95% CI) 0.06–0.15]), with no increase observed with time of exposure. The age‐ and sex‐adjusted SIR of lymphoma was 2.62 (95% CI 1.58–4.09) (Surveillance, Epidemiology, and End Results [SEER] program database). The clinical characteristics of the 19 lymphomas were typical for the RA population. Three lymphomas were positive for Epstein‐Barr virus, 8 were negative, 2 were equivocal, and 6 were untested. Numerically, more lymphoma cases had a history of Sjögren's syndrome and were positive for anti–cyclic citrullinated protein and rheumatoid factor at baseline versus matched controls. The mean corticosteroid dose was higher for lymphoma cases versus controls.

Conclusion

In the tofacitinib RA clinical development program, lymphoma rates were stable over time and there were minimal differences in the baseline characteristics of patients with and without lymphoma.
Efficacy of a Work Disability Prevention Program for People with Rheumatic and Musculoskeletal Conditions: A Single‐Blind Parallel‐Arm Randomized Controlled Trial
Authors: Keysor Julie J. , LaValley Michael P. , Brown Carrie , Felson David T. , AlHeresh Rawan A. , Vaughan Molly W. , Yood Robert , Reed John I. , Allaire Saralynn J.
Published: September 2017

Objective

Work disability rates are high among people with rheumatic and musculoskeletal conditions. Effective disability preventive programs are needed. We examined the efficacy of a modified vocational rehabilitation approach delivered by trained occupational therapists and physical therapists on work limitation and work loss over 2 years among people with rheumatic and musculoskeletal conditions.

Methods

Eligibility criteria for this single‐blind, parallel‐arm randomized trial included ages 21–65 years, 15 or more hours/week employment, a self‐reported doctor‐diagnosed rheumatic or musculoskeletal condition, and concern about staying employed. The intervention consisted of a 1.5‐hour meeting, an action plan, written materials on employment supports, and telephone calls at 3 weeks and 3 months. Control group participants received the written materials. The primary outcome was the Work Limitations Questionnaire (WLQ) output job demand subscale. The secondary outcome was work loss. Intent‐to‐treat analyses were performed.

Results

Between October 2011 and January 2014, 652 individuals were assessed for eligibility. A total of 287 participants were randomized: 143 intervention and 144 control participants. In total, 264 participants (92%) completed 2‐year data collection. There was no difference in the mean ± SD WLQ change scores from baseline to 2‐year followup (−8.6 ± 1.9 intervention versus −8.3 ± 2.2 control; P = 0.93). Of the 36 participants who experienced permanent work loss at 2 years, 11 (8%) were intervention participants and 25 (18%) control participants (P = 0.03).

Conclusion

The intervention did not have an effect on work limitations but reduced work loss. The intervention can be delivered by trained rehabilitation therapists.
Nanomaterials in the Prevention, Diagnosis, and Treatment of Mycobacterium Tuberculosis Infections
Authors: Xu Kaijin , Liang Zhen Chang , Ding Xin , Hu Haiyang , Liu Shaoqiong , Nurmik Martin , Bi Sheng , Hu Feishu , Ji Zhongkang , Ren Jingjing , Yang Shigui , Yang Yi Yan , Li Lanjuan
Published: September 2017

Despite the tremendous advancements that have been made in biomedical research, Mycobacterium tuberculosis (TB) still remains one of the top 10 causes of death worldwide, outpacing the Human Immunodeficiency Virus as a leading cause of death from an infectious disease. In the light of such significant disease burden, tremendous efforts have been made worldwide to stem this burgeoning spread of disease. The use of nanomaterials in TB management has increased in the past decade, particularly in the areas of early TB detection, prevention, and treatment. Nanomaterials have been proven to be efficacious in the rapid and accurate detection of TB pathogens. Novel nanocarriers have also shown tremendous promise in improving drug delivery, potentially enhancing drug concentrations in target organs while at the same time, reducing treatment frequency. In addition, the engineering of antigen nanocarriers represents an exciting front in TB research, potentially paving the way for the successful development of a new class of effective TB vaccines. This article discusses epidemiology and pathogenesis of TB infections, current TB therapeutics, advanced nanomaterials for anti‐TB drug delivery, and TB vaccines. In addition, challenges and future perspectives in developing safe and effective nanomaterials in TB diagnosis and therapy are also presented.
Biodegradable Shape Memory Polymers in Medicine
Authors: Peterson Gregory I. , Dobrynin Andrey V. , Becker Matthew L.
Published: September 2017

Shape memory materials have emerged as an important class of materials in medicine due to their ability to change shape in response to a specific stimulus, enabling the simplification of medical procedures, use of minimally invasive techniques, and access to new treatment modalities. Shape memory polymers, in particular, are well suited for such applications given their excellent shape memory performance, tunable materials properties, minimal toxicity, and potential for biodegradation and resorption. This review provides an overview of biodegradable shape memory polymers that have been used in medical applications. The majority of biodegradable shape memory polymers are based on thermally responsive polyesters or polymers that contain hydrolyzable ester linkages. These materials have been targeted for use in applications pertaining to embolization, drug delivery, stents, tissue engineering, and wound closure. The development of biodegradable shape memory polymers with unique properties or responsiveness to novel stimuli has the potential to facilitate the optimization and development of new medical applications.
Aerosol‐Jet Printed Fillets for Well‐Formed Electrical Connections between Different Leveled Surfaces
Authors: Gu Yuan , Hines Daniel R. , Yun Victor , Antoniak Michael , Das Siddhartha
Published: September 2017

As additive manufacture becomes more prevalent in the fabrication of advanced electronics, there is a need to create well‐formed, robust circuitization, and interconnects between components mounted onto different leveled surfaces (DLSs). Here, an algorithm is developed for aerosol‐jet printing of fillet structures that enable such a circuitization and hence a smooth electrical transition between the DLSs. The fillets are printed using an ultraviolet‐curable polymer ink in the presence of in situ curing. A specific deposition rate is established in order to ensure a precise architecture. Further, a surface smoothing technique is employed to smooth out the stepped surface topology of a fillet resulting from the layer‐by‐layer printing of in situ cured material. Finally, it is ascertained that the performance of these printed fillets is highly satisfactory by carrying out the resistance measurements of the conducting lines printed over these fillet structures both before and after temperature cycling and establishing the mechanical stability of the fillets by employing an adhesion test. This technology ensures that the fillets not only establish a mechanical integration/attachment of the two DLSs, but more importantly that they also provide a well‐formed surface onto which an electrical connection between these two DLSs can be established.
g‐C3N4‐Based Heterostructured Photocatalysts
Authors: Fu Junwei , Yu Jiaguo , Jiang Chuanjia , Cheng Bei
Published: September 2017

Photocatalysis is considered as one of the promising routes to solve the energy and environmental crises by utilizing solar energy. Graphitic carbon nitride (g‐C3N4) has attracted worldwide attention due to its visible‐light activity, facile synthesis from low‐cost materials, chemical stability, and unique layered structure. However, the pure g‐C3N4 photocatalyst still suffers from its low separation efficiency of photogenerated charge carriers, which results in unsatisfactory photocatalytic activity. Recently, g‐C3N4‐based heterostructures have become research hotspots for their greatly enhanced charge carrier separation efficiency and photocatalytic performance. According to the different transfer mechanisms of photogenerated charge carriers between g‐C3N4 and the coupled components, the g‐C3N4‐based heterostructured photocatalysts can be divided into the following categories: g‐C3N4‐based conventional type II heterojunction, g‐C3N4‐based Z‐scheme heterojunction, g‐C3N4‐based p–n heterojunction, g‐C3N4/metal heterostructure, and g‐C3N4/carbon heterostructure. This review summarizes the recent significant progress on the design of g‐C3N4‐based heterostructured photocatalysts and their special separation/transfer mechanisms of photogenerated charge carriers. Moreover, their applications in environmental and energy fields, e.g., water splitting, carbon dioxide reduction, and degradation of pollutants, are also reviewed. Finally, some concluding remarks and perspectives on the challenges and opportunities for exploring advanced g‐C3N4‐based heterostructured photocatalysts are presented.
Does Point‐of‐care Ultrasound Affect Patient and Caregiver Satisfaction for Children Presenting to the Pediatric Emergency Department?
Authors: Lin Margaret J. , Neuman Mark I. , Monuteaux Michael , Rempell Rachel
Published: September 2017

Objectives

Point‐of‐care ultrasound (POCUS) may facilitate the diagnosis and management of children for various conditions. Integration of POCUS into clinical care requires hands‐on training; however, providers may be reluctant to perform educational ultrasounds to improve their skills, as it is a procedure without direct clinical benefit to the patient and due to concerns that it may lower a family's overall satisfaction. We sought to evaluate whether the use of POCUS changed overall patient/caregiver satisfaction in a pediatric emergency department (ED) visit.

Methods

We performed a prospective cohort study of children presenting to a single children's hospital ED. We evaluated overall satisfaction for three groups: 1) children undergoing POCUS for educational purposes, 2) children undergoing POCUS for a specific diagnostic indication, and 3) controls who did not receive POCUS. Overall satisfaction was measured using a 100‐point visual analog scale (VAS). We performed a noninferiority test between patients receiving POCUS and controls using a delta of 10 points to determine significance. We also examined satisfaction among patients receiving diagnostic ultrasound and sought to determine patient/caregiver satisfaction with specific elements of the POCUS experience.

Results

We surveyed 159 patients who presented between April 2016 and August 2016 (53 in each group). The three groups did not differ with respect to patient age, sex, or Emergency Severity Index level. The median VAS scores for both the educational and the diagnostic POCUS groups (94 and 94, respectively) were not inferior to the VAS score for the control group (91) with a median (95% confidence interval [CI]) difference of 3.0 (–2.2 to 8.2) for educational and control groups and 3.0 (–1.6 to 7.6) for diagnostic and control groups. No patients/caregivers in the educational POCUS group would refuse an educational ultrasound during a future medical encounter.

Conclusion

Educational POCUS does not decrease patient/caregiver satisfaction among children presenting to the ED.
Efficiency of Egyptian organic agriculture: A local maximum likelihood approach
Authors: Guesmi Bouali , Serra Teresa , Radwan Amr , Gil José María
Published: September 2017

Productive efficiency analysis is a relevant tool that can be used to evaluate differences in the performance between conventional and organic farms. Such study is important for the assessment of the economic viability of these two agricultural systems. Although the existing research has widely used the stochastic frontier methodology and the data envelopment analysis nonparametric approach to assess farming performance, the use of the local maximum likelihood (LML) approach proposed by Kumbhakar et al. is scarce. This study represents the first analysis that compares the efficiency levels of organic and conventional farms in Egypt. To do so, we apply LML methods to cross‐sectional, farm‐level data collected from a sample of 60 Egyptian farms. Results suggest that performance of organic farmers is slightly better than performance of their conventional counterparts. Further, we find a positive relationship between technical efficiency and farm size. [EconLit citations: C14, Q12, D24].
Flow dynamics in Taylor–Couette flow reactor with axial distribution of temperature
Authors: Masuda Hayato , Yoshida Saho , Horie Takafumi , Ohmura Naoto , Shimoyamada Makoto
Published: September 2017

In this study, the flow dynamics of a Taylor–Couette flow with an axial distribution of temperature was experimentally investigated. The flow can be classified into three patterns based on the balance between the centrifugal force and the buoyancy. If the buoyancy is dominant, global heat convection is observed instead of Taylor vortices (Case I). When the buoyancy is comparable to the centrifugal force, the Taylor vortices and global heat convection appear alternately (Case II). If the centrifugal force is sufficiently high to suppress the buoyancy, stable Taylor vortices are observed (Case III). The characteristics of the mixing/diffusion are investigated by conducting a decolorization experiment on a passive tracer. In Case II, the tracer is rapidly decolorized in the presence of the global heat convection instead of the Taylor vortices. This result implies that the interaction between the centrifugal force and the buoyancy would induce an anomalous transport. © 2017 American Institute of Chemical EngineersAIChE J, 64: 1075–1082, 2018
A new insight into the stability of variable viscosity diffusive boundary layers in porous media under gravity field
Authors: Sabet Nasser , Hassanzadeh Hassan , Abedi Jalal
Published: September 2017

We study the stability of gravitationally unstable transient diffusive boundary layers with variable viscosity in porous media. The previous studies characterize the effect of viscosity variation only in terms of viscosity contrast and generalize their findings. However, conclusions of different studies seem contradictory. Our results demonstrate that stability of diffusive fronts is governed by the boundary layer viscosity and not solely by the viscosity contrast. In other words, the use of viscosity contrast to ascertain the stability of the system cannot be generalized. Nonlinear simulations are conducted based on a finite difference scheme to validate the results of linear stability analysis for which the amplification theory is adopted. We also revisit other available scaling approaches used to characterize the effect of viscosity variation on the onset of convective dissolution and explain why previously made conclusions are not inclusive and sometimes appeared to be contradictory. A critical Rayleigh number is found to predict stability of Rayleigh‐Darcy convection in a porous layer with variable viscosity. The results reveal that this critical value can differ highly from the conventional value of 4π2. © 2017 American Institute of Chemical Engineers AIChE J, 64: 1083–1094, 2018
Confirmation that RIPK4 mutations cause not only Bartsocas‐Papas syndrome but also CHAND syndrome
Authors: Busa Tiffany , Jeraiby Mohammed , Clémenson Alix , Manouvrier Sylvie , Granados Viviana , Philip Nicole , Touraine Renaud
Published: September 2017

CHAND syndrome is an autosomal recessive disorder characterized by curly hair, ankyloblepharon, and nail dysplasia. Only few patients were reported to date. A homozygous RIPK4 mutation was recently identified by homozygosity mapping and whole exome sequencing in three patients from an expanded consanguineous kindred with a clinical diagnosis of CHAND syndrome. RIPK4 was previously known to be implicated in Bartsocas‐Papas syndrome, the autosomal recessive form of popliteal pterygium syndrome. We report here two cases of RIPK4 homozygous mutations in a fetus with severe Bartsocas‐Papas syndrome and a patient with CHAND syndrome. The patient with CHAND syndrome harbored the same mutation as the one identified in the family previously reported. We thus confirm the implication of RIPK4 gene in CHAND syndrome in addition to Bartsocas‐Papas syndrome and discuss genotype/phenotype correlations.
The spectrum of DNMT3A variants in Tatton–Brown–Rahman syndrome overlaps with that in hematologic malignancies
Authors: Shen Wei , Heeley Jennifer M. , Carlston Colleen M. , Acuna‐Hidalgo Rocio , Nillesen Willy M. , Dent Karin M. , Douglas Ganka V. , Levine Kara L. , Bayrak‐Toydemir Pinar , Marcelis Carlo L. , Shinawi Marwan , Carey John C.
Published: September 2017

De novo, germline variants in DNMT3A cause Tatton–Brown–Rahman syndrome (TBRS). This condition is characterized by overgrowth, distinctive facial appearance, and intellectual disability. Somatic DNMT3A variants frequently occur in hematologic malignances, particularly acute myeloid leukemia. The Arg882 residue is the most common site of somatic DNMT3A variants, and has also been altered in patients with TBRS. Here we present three additional patients with this disorder attributed to DNMT3A germline variants that disrupt the Arg882 codon, suggesting that this codon may be a germline mutation hotspot in this disorder. Furthermore, based on the investigation of previously reported variants in patients with TBRS, we found overlap in the spectrum of DNMT3A variants observed in this disorder and somatic variants in hematological malignancies.
The Full Pressure–Temperature Phase Envelope of a Mixture in 1000 Microfluidic Chambers
Authors: Xu Yi , Riordon Jason , Cheng Xiang , Bao Bo , Sinton David
Published: September 2017

Knowing the thermodynamic state of complex mixtures—liquid, gas, supercritical or two‐phase—is essential to industrial chemical processes. Traditionally, phase diagrams are compiled piecemeal from individual measurements in a pressure–volume–temperature cell performed in series, where each point is subject to a long fluid equilibrium time. Herein, 1000 microfluidic chambers, each isolated by a liquid piston and set to a different pressure and temperature combination, provide the complete pressure–temperature phase diagram of a hydrocarbon mixture at once, including the thermodynamic phase envelope. Measurements closely match modeled values, with a standard deviation of 0.13 MPa between measurement and model for the dew and bubble point lines, and a difference of 0.04 MPa and 0.25 °C between measurement and model for the critical point.