bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylactic Use of Factor VIII: an Economic Evaluation
Authors: Bohn Rhonda L. , Avorn Jerry , Glynn Robert J. , Choodnovskiy Igor , Haschemeyer Rudy , Aledort Louis M.
Published: May 2019

Background: Since the introduction of exogenous factor VIII therapy, several studies have explored the clinical benefits of prophylactic use of factor VIII. Little research, though, has focused on the economic aspects of this regimen. We conducted a cost analysis using data from the Orthopedic Outcomes Study, a prospective, cross-national study of the clinical outcomes associated with different patterns of factor VIII utilization to examine the health care costs incurred and expenditures averted in patients receiving on-demand versus prophylactic use of factor VIII in hemophilia. Methods and Analysis: 831 patients with severe hemophilia aged 1 to 31 years, from 19 centers around the world were included in the cost analysis. Patients were categorized into three groups according to the number of weeks during the study years in which they received prophylactic regimens of factor VIII. For each subject, we estimated the costs of hospitalization, surgery, days lost from school or work, and factor VIII utilization. Costs were then stratified by age and by joint score to assess confounding, and a multivariate model developed to determine the relationship between use of factor VIII prophylaxis and total costs, while controlling for potential confounders.

Results: Patients who received factor VIII episodically incurred substantially greater disability-related costs (days lost from school or work, days hospitalized due to hemophilia, surgery) than patients who received factor VIII prophylactically for some or all of the study period. For all treatment regimens, most disability-related costs were accounted for by hospitalization for hemophilia-related conditions. The cost of factor VIII itself was substantial in all treatment categories but was highest among patients who received year-round prophylaxis, exceeding the savings resulting from reduced disability and other health care expenditures.

Conclusions: Reductions in non-factor health care costs and disability associated with prophylactic use of factor VIII in hemophilia were substantial and helped somewhat to offset the much higher costs of this regimen. For certain subgroups, frequent episodic treatment may be more expensive than full-time prophylaxis. However, because of the very high cost of year-round prophylactic use of factor VIII, total health care expenditures were highest among patients receiving this therapeutic regimen. However, because prophylaxis clearly offers important clinical benefits, this approach may be warranted on medical rather than economic grounds.
Stimulation by G Protein βγ Subunits of Phospholipase C β Isoforms in Human Platelets
Authors: Banno Yoshiko , Asano Tomiko , Nozawa Yoshinori
Published: May 2019

Different phospholipase C (PLC) isoforms were located in human platelet cytosol and membranes. PLCγ2 and PLCβ3b were mainly located in the cytosol and PLCβ2 and PLCβ3a were in both cytosol and membranes by using specific antibodies against PLC isozymes (Banno Y, Nakashima S, Ohzawa M, Nozawa Y. J Biol Chem 1996; 271: 14989-94). Three PLC fractions activated by G protein βγ subunits were purified from human platelet cytosol and membrane fractions. Two PLC fractions from membranes were identified as PLCβ2 and PLCβ3a, and one from cytosol was PLCβ3b. These PLCβ isoforms were activated by the purified βγ subunits of brain G proteins in the order PLCβ3b > PLCβ3a > PLCβ2. Western blot analysis of γ subunits of the purified platelet G proteins with antibodies against various standard γ subunits revealed that the major component of the γ subunit of Gi2 and Gq was γ5, and that γ7 was a minor component. Studies using various subtypes of βγ subunits, βγ2, βγ3, and βγ7 purified from bovine brain, βγ5 from bovine lung, or βγ12 from bovine spleen, failed to show differences in their ability to stimulate the isolated platelet PLCβ isoforms. These results suggest that the βγ subunits of Gi2 and Gq have similar efficacy in regulation of effectors in human platelets.
Attenuation of Tissue Thrombosis and Hemorrhage by ala-TFPI Does not Account for Its Protection against E. coli
Authors: Randolph M. M. , White G. L. , Kosanke S. D. , Bild G. , Carr C. , Galluppi G. , Hinshaw L. B. , Taylor F. B.
Published: May 2019

This study was designed to determine the effect of a delayed infusion (T+120 min) of alanyl tissue factor pathway inhibitor (ala-TFPI) on the response to LD100 E. coli. We hypothesized that baboons treated with a low dose of TFPI (5 mg/kg) which did not survive would exhibit thrombosis, infarction and hemorrhage of target tissues such as that seen in untreated animals infused with LD100 E. coli. Eight baboons were infused with 5 mg/kg of ala-TFPI over a 10 h period beginning immediately after a 2 h infusion of LD100 E. coli (experimental group). Four baboons were infused with E. coli followed by a 10 h infusion of saline (control group). Of the 12 baboons, the 11 non-survivors (TFPI = 7 out of 8; controls = 4 out of 4) were evaluated for the extent of thrombosis, necrosis, hemorrhage, and congestion of target tissues and for changes in clinical chemical parameters. We expected that failure to protect would correlate with failure to inhibit thrombosis of target tissue (8). Surprisingly ala-TFPI significantly inhibited thrombosis, hemorrhage and necrosis of adrenal and renal tissues and attenuated the rise in creatinine in the 7 treated non-survivors. The lungs of these non-survivors, however, exhibited intra-alveolar fibrin and a mild degree of hemorrhage and edema. We concluded that low doses of ala-TFPI begun as late as T+120 in minutes failed to protect against the lethal effects of LD100 E. coli in spite of completely preventing thrombosis and hemorrhage in target organs, and that thrombosis, infarction and hemorrhage of adrenal and renal tissue are not part of the lethal chain of events in this IV model of E. coli sepsis.
Peripheral Giant Cell Granuloma: A Case Report with Review on Its Histogenesis and Recurrence
Authors: Jindal Deepti Garg , Kushwaha Sandhya Singh , Joshi Sonia , Sepolia Namita , Jindal Varun , Jain Kanu
Published: May 2019

Giant cell granulomas (GCGs) of the jaws are non-neoplastic lesions that arise either peripherally in periodontal ligament, mucoperiosteum, or centrally in the bone. Histologically, both peripheral and central giant cell granuloma are characterized by the presence of numerous multinucleated giant cells in a prominent fibrous stroma. Peripheral giant cell granuloma is an infrequent reactive, exophytic lesion of the oral cavity, also known as giant-cell epulis, osteoclastoma, giant cell reparative granuloma, or giant cell hyperplasia. It is the most common giant cell lesion of the jaws and originates from the connective tissue of the periosteum or from the periodontal membrane, in response to local irritation or chronic trauma. The lesion develops mostly in adults, commonly in the lower jaw, with slight female predilection although is uncommon in children. Clinically, it shows resemblance to pyogenic granuloma, peripheral ossifying fibroma, and many other peripheral lesions seen in the oral cavity, but in our case it resembled a squamous cell carcinoma, thereby histopathology is mandatory for the diagnosis of this lesion. The lesion although being relatively common, still has a lot of ambiguity. The ambiguity is in terms of its etiology, growth potential, biological behavior (recurrence), histogenesis of its cells, and its treatment. The entity further holds significance because of its notorious behavior and high tendency to recur. This is a case report of a 30-year-old female patient with history of swelling in the lower anterior region of jaw since 1 year. After complete excision of lesion, lesion reoccurred after few months.
Assessment of Intravitreal Injection Training among U.S.-Based Ophthalmology Residents
Authors: Liechty Jacob J. , Wilkinson Michael J. , Bowie Esther M.
Published: May 2019

Purpose To describe the intravitreal injection training of ophthalmology residents in the United States in 2018.

Design Cross-sectional survey.

Methods An anonymous, 29-question, internet-based survey was emailed to 119 ophthalmology residency program directors with the instructions to forward the survey to their ophthalmology residents.

Results A total of 117 ophthalmology residents (7.89%) responded to the survey. The majority of residents stated that their intravitreal injection training began during their first year of ophthalmology training, PGY 2 year, (92.3%). The majority of residents performed at least 25 injections per year (78.6%). All residents use antiseptic on the conjunctiva prior to the injection, 94% use a lid speculum, and 84.6% avoided talking in the procedure room. Most injections are performed with gloves (83.8%). A minority of residents stated that they are trained to use povidone-iodine on the eyelids prior to performing an injection (45.3%). Only 6.0% of residents claimed to use postinjection antibiotic drops. Performance of bilateral, simultaneous intravitreal injections was split with nearly half of residents not being trained in this method (47.9%).

Conclusion Ophthalmology residents from across the country experience a variety of different injection protocols when being trained on how to perform intravitreal injections. Conjunctival antisepsis has reached a clear consensus while topics such as simultaneous, bilateral injections and eyelid antisepsis are still uncertain among the resident community.
Closure in J. M. Coetzee’sDisgrace
Authors: Dibavar Sara Saei , Abbasi Pyeaam , Pirnajmuddin Hossein
Published: May 2019

This article explores the politics of J. M. Coetzee’s writing style inDisgrace. Drawing on Marie-Laure Ryan’s theory of textual universe and Barbara Dancygier’s narrative space construction strategies, we argue that Coetzee’s narrative is set up to expose David Lurie’s deliberately distorted self-representation. Indeed, the conflict between the protagonist’s private worlds and the textual actual world (TAW) results from the protagonist’s distorting of the TAW by his deliberately distorted self-representation clouding his judgment and, accordingly, his so-called knowledge worlds (K-worlds). Also discussed is the process through which the protagonist is brought to a reckoning – not grace – through ontological re-orientation by undergoing a three-step process of social stigmatization, recognizing his vulnerability and situatedness, and coming to terms with his actual environment (TAW).
A diachronic keyword analysis in research article titles and cited article titles in applied linguistics from 1990 to 2016
Authors: Yang Wenhsien
Published: May 2019

Due to the competitiveness in academic publication and the emerging heavy reliance on Internet search engines to expand visibility and readership and to promote publications, writing an attractive and appropriate research article title is essential. In addition, titles may be the first aspect of papers evaluated by journal editors in their screening of submissions in order to meet the requirements of the target audience. These demands call for the use of various academic writing skills, and thus make writing titles challenging. Research on structuring journal article titles has been extensively conducted across disciplines, but what keywords (i.e. lexical items highly distinctive of the titles) are employed to reflect current knowledge and receive high citations is still under-researched. To bridge this gap, the present corpus-driven research collected and investigated titles written in leading applied linguistics journals over 25 years to identify their keywords. These were compared to different time spans to study the significance and relevance of the domain knowledge. The most frequently cited articles were also selected to study how their titles relate to keyword use and to investigate their impact on the domain knowledge. The results reveal that keywords vary in accordance with the research trends over time. In addition, while titles are becoming longer, more keywords are employed by authors in order to expand the paper’s visibility and enhance the citations. The pedagogical implications for teaching academic writing, and suggestions for researching this appendant genre are provided.
Low-protein diet enhances adiponectin secretion in rats
Authors: Yagi Takashi , Toyoshima Yuka , Tokita Reiko , Taguchi Yusuke , Okamoto Yoshihisa , Takahashi Shin-Ichiro , Kato Hisanori , Minami Shiro
Published: May 2019

Previous studies including ours have shown that a low-protein diet up-regulates insulin signaling in the liver and muscle and induces fatty liver in rats. Adiponectin is known as an insulin-sensitizing adipocytokine. We, therefore, examined the effect of a low-protein diet on the adiponectin levels in rats. The low-protein diet significantly increased serum adiponectin level. However, mRNA and protein levels of adiponectin in white adipose tissue (WAT) were not changed by the low-protein diet. Since it is known that oligomerization is important to control serum adiponectin level, we examined the population of adiponectin oligomeric forms in WAT and found that low-protein diet did not change it. Despite these events, the amount of its secretion was significantly increased in the adipocytes isolated from WAT of low-protein diet-fed rats. These results indicate that a low-protein diet enhances adiponectin secretion, which is not due to the increased intracellular amount and oligomerization of adiponectin.
Use of Autofluorescence to Intraoperatively Diagnose Visceral Pleural Invasion From Frozen Sections in Patients With Lung Adenocarcinoma 2 cm or Less
Authors: Xie Huikang , Su Hang , Chen Donglai , Xie Dong , Dai Chenyang , Ren Yijiu , She Yunlang , Xu Long , Zhao Shengnan , Wu Chunyan , Jiang Gening , Chen Chang
Published: May 2019

Objectives

We prospectively investigate the accuracy of frozen sections for diagnosing visceral pleural invasion (VPI) by autofluorescence and evaluated its usefulness in sublobar resection.

Methods

We included patients with lung adenocarcinoma 2 cm or less to evaluate the diagnostic performance of autofluorescence for VPI in frozen sections via a fluorescence microscope. Furthermore, the impact of VPI on patients treated with sublobar resection was assessed in another cohort.

Results

A total of 112 patients were enrolled. The accuracy, sensitivity, and specificity of autofluorescence for VPI diagnosis was 95.5%, 86.8%, and 100%, respectively. Sublobar resection was an independent risk factor for recurrence in patients with lung adenocarcinomas 2 cm or less with VPI positivity (hazard ratio, 3.30; P = .023), whereas it was not in those with VPI negativity.

Conclusions

Using autofluorescence in frozen sections appears to be an accurate method for diagnosing VPI, which is helpful for surgical decision making.
deconvSeq: deconvolution of cell mixture distribution in sequencing data
Authors: Du Rose , Carey Vince , Weiss Scott T
Published: May 2019

Motivation

Although single-cell sequencing is becoming more widely available, many tissue samples such as intracranial aneurysms are both fibrous and minute, and therefore not easily dissociated into single cells. To account for the cell type heterogeneity in such tissues therefore requires a computational method. We present a computational deconvolution method, deconvSeq, for sequencing data (RNA and bisulfite) obtained from bulk tissue. This method can also be applied to single-cell RNA sequencing data.

Results

DeconvSeq utilizes a generalized linear model to model effects of tissue type on feature quantification, which is specific to the data structure of the sequencing type used. Estimated model coefficients can then be used to predict the cell type mixture within a tissue. Predicted cell type mixtures were validated against actual cell counts in whole blood samples. Using this method, we obtained a mean correlation of 0.998 (95% CI 0.995–0.999) from the RNA sequencing data of 35 whole blood samples and 0.95 (95% CI 0.91–0.98) from the reduced representation bisulfite sequencing data from 35 whole blood samples. Using symmetric balances to obtain the correlation between compositional parts, we found that the lowest correlation occurred for monocytes for both RNA and bisulfite sequencing. Comparison with other methods of decomposition such as deconRNAseq, CIBERSORT, MuSiC and EpiDISH showed that deconvSeq is able to achieve good prediction using mean correlation with far fewer genes or CpG sites in the signature set.

Availability and implementation

Software implementing deconvSeq is available at https://github.com/rosedu1/deconvSeq.

Supplementary information

Supplementary data are available at Bioinformatics online.
Freezing of gait in Parkinson’s disease reflects a sudden derangement of locomotor network dynamics
Authors: Pozzi Nicoló G , Canessa Andrea , Palmisano Chiara , Brumberg Joachim , Steigerwald Frank , Reich Martin M , Minafra Brigida , Pacchetti Claudio , Pezzoli Gianni , Volkmann Jens , Isaias Ioannis U
Published: May 2019

Freezing of gait is a disabling symptom of Parkinson’s disease that causes a paroxysmal inability to generate effective stepping. The underlying pathophysiology has recently migrated towards a dysfunctional supraspinal locomotor network, but the actual network derangements during ongoing gait freezing are unknown. We investigated the communication between the cortex and the subthalamic nucleus, two main nodes of the locomotor network, in seven freely-moving subjects with Parkinson’s disease with a novel deep brain stimulation device, which allows on-demand recording of subthalamic neural activity from the chronically-implanted electrodes months after the surgical procedure. Multisite neurophysiological recordings during (effective) walking and ongoing gait freezing were combined with kinematic measurements and individual molecular brain imaging studies. Patients walked in a supervised environment closely resembling everyday life challenges. We found that during (effective) walking, the cortex and subthalamic nucleus were synchronized in a low frequency band (4–13 Hz). In contrast, gait freezing was characterized in every patient by low frequency cortical-subthalamic decoupling in the hemisphere with less striatal dopaminergic innervation. Of relevance, this decoupling was already evident at the transition from normal (effective) walking into gait freezing, was maintained during the freezing episode, and resolved with recovery of the effective walking pattern. This is the first evidence for a decoding of the networked processing of locomotion in Parkinson’s disease and suggests that freezing of gait is a ‘circuitopathy’ related to a dysfunctional cortical-subcortical communication. A successful therapeutic approach for gait freezing in Parkinson’s disease should aim at directly targeting derangements of neural network dynamics.
Resilience and social cohesion through the lens of residents in a Kenyan informal settlement
Authors: Vertigans Stephen , Gibson Neil
Published: May 2019

Over recent years, resilient attitudes and behaviour are widely seen within the Global North to be potential solutions to community developmental challenges. Although greater international emphasis is being placed on ‘bottom up’ approaches, learning from existing levels of resilience among communities such as residents in informal settlements has aroused limited attention. Instead analysis of informal settlements tends to concentrate on the multitude of environmental, economic and social problems that many communities share and internationally derived normative solutions. To help address this relative neglect, research was designed that sought more information about local experiences, people and processes that have been instrumental in building levels of resilience that help overcome challenges and improve well-being. Using the photovoice methodological technique, a project was developed to capture experiences of participants in Kibera, Nairobi. Participants were young people and either role models or had the potential to be. In so doing the project was participant driven, learning from residents about who and what have been influential in the development and maintenance of resilience. The results highlighted the particular significance of social cohesion and, in particular, relationships and attachment to place.
Beethoven’s pianoforte damper pedalling: a case of double notational style
Authors: Miucci Leonardo
Published: May 2019

This article challenges the so-called ‘Urtext’ approach whereby performers aim to play no more and no less than is notated in an authoritative edition. With reference to Beethoven’s pedalling, it shows that he provided no pedal markings in the authorised editions of his piano sonatas before op.26 (1801), which constitute nearly a third of his output in this genre. After this point, however, his notation evolved, and he began indicating pedal markings with increasing intensity. The article traces practices of piano pedalling as indicated in keyboard treatises around 1800 and also as revealed in Beethoven’s ‘Kafka sketchbook’. It argues that the authorised editions of his sonatas show a double notational style. Beethoven did not add pedal markings for passages where he expected his players to use the pedal according to convention. Instead his pedal markings indicate locations where usage of the pedal contravened conventions such as harmonic clarity.
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes
Authors: Liang Lina , Li Xia , Moutton Sébastien , Schrier Vergano Samantha A , Cogné Benjamin , Saint-Martin Anne , Hurst Anna C E , Hu Yushuang , Bodamer Olaf , Thevenon Julien , Hung Christina Y , Isidor Bertrand , Gerard Bénédicte , Rega Adelaide , Nambot Sophie , Lehalle Daphné , Duffourd Yannis , Thauvin-Robinet Christel , Faivre Laurence , Bézieau Stéphane , Dure Leon S , Helbling Daniel C , Bick David , Xu Chengqi , Chen Qiuyun , Mancini Grazia M S , Vitobello Antonio , Wang Qing Kenneth
Published: May 2019

KCNMA1 encodes the large-conductance Ca2+- and voltage-activated K+ (BK) potassium channel α-subunit, and pathogenic gain-of-function variants in this gene have been associated with a dominant form of generalized epilepsy and paroxysmal dyskinesia. Here, we genetically and functionally characterize eight novel loss-of-function (LoF) variants of KCNMA1. Genome or exome sequencing and the participation in the international Matchmaker Exchange effort allowed for the identification of novel KCNMA1 variants. Patch clamping was used to assess functionality of mutant BK channels. The KCNMA1 variants p.(Ser351Tyr), p.(Gly356Arg), p.(Gly375Arg), p.(Asn449fs) and p.(Ile663Val) abolished the BK current, whereas p.(Cys413Tyr) and p.(Pro805Leu) reduced the BK current amplitude and shifted the activation curves toward positive potentials. The p.(Asp984Asn) variant reduced the current amplitude without affecting kinetics. A phenotypic analysis of the patients carrying the recurrent p.(Gly375Arg) de novo missense LoF variant revealed a novel syndromic neurodevelopmental disorder associated with severe developmental delay, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic dysmorphic features. Patients with other LoF variants presented with neurological and developmental symptoms including developmental delay, intellectual disability, ataxia, axial hypotonia, cerebral atrophy and speech delay/apraxia/dysarthria. Therefore, LoF KCNMA1 variants are associated with a new syndrome characterized by a broad spectrum of neurological phenotypes and developmental disorders. LoF variants of KCNMA1 cause a new syndrome distinctly different from gain-of-function variants in the same gene.
P-Partitions and p-Positivity
Authors: Alexandersson Per , Sulzgruber Robin
Published: May 2019

Using the combinatorics of $\alpha$-unimodal sets, we establish two new results in the theory of quasisymmetric functions. First, we obtain the expansion of the fundamental basis into quasisymmetric power sums. Secondly, we prove that generating functions of reverse $P$-partitions expand positively into quasisymmetric power sums. Consequently, any nonnegative linear combination of such functions is $p$-positive whenever it is symmetric. As an application, we derive positivity results for chromatic quasisymmetric functions, unicellular and vertical strip LLT polynomials, multivariate Tutte polynomials, and the more general $B$-polynomials, matroid quasisymmetric functions, and certain Eulerian quasisymmetric functions, thus reproving and improving on numerous results in the literature.
Outcomes by sex following treatment initiation with darunavir/cobicistat in a large Spanish cohort of the CODAR study (GeSIDA 9316)
Authors: Pérez Elías M J , Alejos B , Vivancos M J , Ribera E , Galindo M J , Vilanova-Trillo L , García-Fraile Fraile L J , de La Fuente Moral S , Garcia De Lomas J , Lozano F , Mateo García M G , Tasias Pitarch M , Diez Martinez M , Rojas J , Raya-Cruz M , Sepúlveda M A , Troya J , Del Campo S , Martinez E ,   CODAR study group, Callau Pilar , Moreno Ana , Casado Jose Luis , Sanchez Javier Martinez , Ayerbe Cristina Gómez , Negredo Dra. Eugenia , Campos Isabel , Puig Jordi , Ribera Esteban , Torrella Ariadna , Planas Bibiana , Knobel Hernando , de Valencia Clinico , Ferrando Ramon , Crespo Manuel , Ocampo Antonio , Sanz José , de los Santos Ignacio , Moreno Alfonso , Díaz Alberto , Martin Carbonero Dra. Luz , de la Torre Javier , Reina Mercedes Rivas , Santos Jesús , María González Domenech Carmen , Gutierrez Dra. Mª Mar , Montero Dra. Marta , Cuéllar Sandra , Boix Vicente , Payeras Antonio , Ryan Pablo , Torralba Miguel , Cuadra Fernando , Aznar Esther , Esteban Herminia , de Miguel Marta , Gonzalez Patricia , Yllescas María
Published: May 2019

Background

Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than triple-based therapies.

Objectives

Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens.

Methods

A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent.

Results

Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes.

Conclusions

No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.
Procedural implications of market definition in platform cases
Authors: Ducci Francesco
Published: May 2019

The central and often neglected problem in the evaluation of competitive effects in platform cases is that the boundaries of the relevant market, usually simply a tool for the analysis of market power, can give raise to substantially different procedural routes depending on whether the antitrust market comprises the platform as a whole or just one side. Based on a comparative assessment across jurisdictions, the article argues that the excessive importance of the relevant market creates a potential mismatch between the economic consequences and doctrinal implications stemming from market definition in multi-sided platform cases. The article concludes that a more desirable framework for evaluating competitive effects should remain independent from the way market definition is carried out.
Decrease in size at maturity of female American lobsters Homarus americanus (H. Milne Edwards, 1837) (Decapoda: Astacidea: Nephropidae) over a 50-year period in Maine, USA
Authors: Waller Jesica D , Reardon Kathleen M , Caron Sarah E , Masters Henry M , Summers Erin L , Wilson Carl J
Published: May 2019

The size at which female American lobsters Homarus americanus (H. Milne Edwards, 1837) reach maturity was determined for females collected from inshore (< 3 nautical miles, or 5.5 km) Boothbay Harbor (BBH), Maine, USA in 2018. A total of 272 females were collected during a three-week period in the spring and each female was assigned a maturity status (immature or mature) based on ovarian staging. These determinations were then compared to two similar female-maturity studies undertaken in BBH by the Maine Department of Marine Resources over the last 50 years. The comparison revealed that the length at which 50% of females reach maturity has decreased by 5 mm over the last 25 years and a significant difference between maturity ogives generated over time in BBH. Cement-gland stage was also recorded for all females and further analysis revealed no significant difference between maturity ogives generated using ovarian and cement-gland staging. Results indicate that cement-gland staging is an effective maturity assessment method in female lobsters from this region. Because there is a well-documented relationship between temperature and size at maturity in crustaceans, we also examined changes in sea-surface temperature during this period in BBH. We found that the region has warmed significantly over this period of time with extreme high temperatures occurring more frequently during the last 25 years. Our results can be used to update key parameters in the stock-assessment model related to growth and egg production in the Gulf of Maine/George’s Bank stock. These findings can also be used to inform future management decisions related to the carapace length of harvested lobsters and the preservation of mature females.
Holocene Population Decline and Conservation Implication for the Western Hercules Beetle, Dynastes grantii (Coleoptera, Scarabaeidae)
Authors: Huang Jen-Pan
Published: May 2019

The Western Hercules beetle (Dynastes grantii) is endemic to the highland forest habitats of southwestern United States and northern Mexico. The habitats harbor many endemic species, but are being threatened by rapid climate change and urban development. In this study, the genetic structure of D. grantii populations from southwestern United States was investigated. Specifically, genomic data from double-digest restriction-site-associated DNA sequencing libraries were utilized to test whether geographically distant populations from the Mogollon Rim (Arizona [N = 12 individuals] and New Mexico [N = 10 individuals]) are genetically structured. The study also estimated the effective population size of the Mogollon Rim populations based on genetic diversity. The results indicated that the 2 geographic populations from the Mogollon Rim were not genetically structured. A population size reduction was detected since the end of the last glacial period, which coincided with a reduction of forest habitat in the study area. The results implied that the connectivity and the size of highland forest habitats in the Mogollon Rim could have been the major factors shaping the population genetic structure and demographic history of D. grantii. The Western Hercules beetle could be a useful flagship species for local natural history education and to promote the conservation of highland forest habitats.
The Impact of Protein Architecture on Adaptive Evolution
Authors: Moutinho Ana Filipa , Trancoso Fernanda Fontes , Dutheil Julien Yann
Published: May 2019

Adaptive mutations play an important role in molecular evolution. However, the frequency and nature of these mutations at the intramolecular level are poorly understood. To address this, we analyzed the impact of protein architecture on the rate of adaptive substitutions, aiming to understand how protein biophysics influences fitness and adaptation. Using Drosophila melanogaster and Arabidopsis thaliana population genomics data, we fitted models of distribution of fitness effects and estimated the rate of adaptive amino-acid substitutions both at the protein and amino-acid residue level. We performed a comprehensive analysis covering genome, gene, and protein structure, by exploring a multitude of factors with a plausible impact on the rate of adaptive evolution, such as intron number, protein length, secondary structure, relative solvent accessibility, intrinsic protein disorder, chaperone affinity, gene expression, protein function, and protein–protein interactions. We found that the relative solvent accessibility is a major determinant of adaptive evolution, with most adaptive mutations occurring at the surface of proteins. Moreover, we observe that the rate of adaptive substitutions differs between protein functional classes, with genes encoding for protein biosynthesis and degradation signaling exhibiting the fastest rates of protein adaptation. Overall, our results suggest that adaptive evolution in proteins is mainly driven by intermolecular interactions, with host–pathogen coevolution likely playing a major role.
A Mn-sensing riboswitch activates expression of a Mn2+/Ca2+ ATPase transporter in Streptococcus
Authors: Martin Julia E , Le My T , Bhattarai Nabin , Capdevila Daiana A , Shen Jiangchuan , Winkler Malcolm E , Giedroc David P
Published: May 2019

Maintaining manganese (Mn) homeostasis is important for the virulence of numerous bacteria. In the human respiratory pathogen Streptococcus pneumoniae, the Mn-specific importer PsaBCA, exporter MntE, and transcriptional regulator PsaR establish Mn homeostasis. In other bacteria, Mn homeostasis is controlled by yybP-ykoY family riboswitches. Here, we characterize a yybP-ykoY family riboswitch upstream of the mgtA gene encoding a PII-type ATPase in S. pneumoniae, suggested previously to function in Ca2+ efflux. We show that the mgtA riboswitch aptamer domain adopts a canonical yybP-ykoY structure containing a three-way junction that is compacted in the presence of Ca2+ or Mn2+ at a physiological Mg2+ concentration. Although Ca2+ binds to the RNA aptamer with higher affinity than Mn2+, in vitro activation of transcription read-through of mgtA by Mn2+ is much greater than by Ca2+. Consistent with this result, mgtA mRNA and protein levels increase ≈5-fold during cellular Mn stress, but only in genetic backgrounds of S. pneumoniae and Bacillus subtilis that exhibit Mn2+ sensitivity, revealing that this riboswitch functions as a failsafe ‘on’ signal to prevent Mn2+ toxicity in the presence of high cellular Mn2+. In addition, our results suggest that the S. pneumoniae yybP-ykoY riboswitch functions to regulate Ca2+ efflux under these conditions.
The Mediation Process: Challenges to Neutrality and the Delivery of Procedural Justice
Authors: De Girolamo Debbie
Published: May 2019

Ethnographic data suggest that the mediator role transcends that of the neutral third-party intervener described in the literature. The mediator becomes part of the mediated negotiation process, at times separate from the parties, aligned with the parties or in opposition to the parties. This is analysed in this article in relation to concepts of neutrality and procedural justice, two concepts much discussed in the mediation literature, often recognised as core features of the mediation process. The justice consciousness of the parties to the process is also explored through ethnographic data for what it reveals about concepts of justice from the parties’ perspective. The article concludes by challenging the dictum of the mediation literature that the process offers procedural justice to its participants.
Nurses Volunteer to Provide Health Care for Migrants
Authors: Sofer Dalia
Published: May 2019

An Arizona shelter offers insight into difficulties some migrants encounter.
Temporary Block to Gag Rule Limiting Access to Family Planning Funding
Authors: Potera Carol
Published: May 2019

Maryland is the first state to fund its own Title X program.
Gout Medication Receives Black Box Warning
Authors: Aschenbrenner Diane S.
Published: May 2019

The gout medication febuxostat (Uloric) now carries a black box warning that it increases the risk of cardiovascular death in people with preexisting cardiovascular disease.

NPs should prescribe febuxostat only if use of allopurinol fails to control gout or isn't tolerated.
Worth Its Weight in Gold
Authors: Robb Jonathan Peter
Published: May 2019

Being a nurse can mean investing emotionally in things you never thought you'd care about.
Navigating Tumultuous Change in the Medical Profession: The Coalition for Physician Accountability
Authors: Chaudhry Humayun J. , Kirch Darrell G. , Nasca Thomas J. , Katsufrakis Peter J. , McMahon Graham T. , Shannon Stephen C. , Ciccone Andrea L.
Published: May 2019

Collaboration among the national organizations responsible for self-regulation in medicine in the United States is critical, as achieving the quadruple aim of enhancing the patient experience and improving population health while lowering costs and improving the work life of clinicians and staff is becoming more challenging. The leaders of the national organizations responsible for accreditation, assessment, licensure, and certification recognize this and have come together as the Coalition for Physician Accountability. The coalition, which meets twice per year, was created in 2011 as a discursive space for group discussion and action related to advancing health care, promoting professional accountability, and improving the education, training, and assessment of physicians. The coalition offers a useful avenue for members to seek common ground and develop constructive, thoughtful solutions to common challenges. Its members have endorsed consensus statements about current topics relevant to health care regulation, advanced innovation in medical school curricula, encouraged a plan for single graduate medical education accreditation for physicians holding MD and DO degrees, supported interprofessional education, championed opioid epidemic mitigation strategies, and supported initiatives responsive to physician workforce shortages, including the Interstate Medical Licensure Compact, an expedited pathway by which eligible physicians may be licensed to practice in multiple jurisdictions.
Cancer Prevention Strategies for Women
Authors: Tergas Ana I. , Wright Jason D.
Published: May 2019

Cancer is the second leading cause of mortality in women. Although treatments have improved, prevention and early detection can have the greatest effect on reducing the burden of cancer in women, with an estimated 40% of cancers being potentially avoidable. Cancers related to smoking, obesity, physical inactivity, alcohol consumption, and poor nutrition account for the largest share of this estimate. This review examines strategies for reducing the burden of cancer in average-risk women. Specifically, we examine primary prevention strategies—those aimed at reducing the risk of developing cancer—as well as secondary prevention strategies—measures aimed at the early detection of disease. Annual well-women examinations are endorsed by the American College of Obstetricians and Gynecologists as opportunities to counsel patients on preventive care or to refer to other specialists for recommended services.
Infections as triggers of flares in systemic autoimmune diseases: novel innate immunity mechanisms
Authors: Torres-Aguilar Honorio , Sosa-Luis Sorely A. , Aguilar-Ruiz Sergio R.
Published: May 2019

Purpose of review

The innate immune response (IIR) has to be immediate facing pathogens, and effective to induce a long-lasting adaptive immunity and immune memory. In genetically susceptible individuals, beyond a first defense, a chronically activated by infections IIR may represent a trigger for the onset or flares in systemic autoimmune diseases. This article reviews the recent scientific literature in this regard and highlights the key issues needing investigation.

Recent findings

Thanks to its high specificity mediated by pattern recognition receptors, the IIR is not called unspecific anymore. The discovery of these increasingly accurate recognizing molecular mechanisms has also evidenced their involvement in breaking self-immune tolerance and to maintain chronic inflammation in autoimmune responses. Neutrophil extracellular traps (NETS) as the main source of antinuclear antibodies; the ‘neutrophils-pDC activation loop’ theory; and the Th1/Th2/Th17 misbalances induced by microbial products because of chronically activated innate immune cells, are some of the recent uncovered IIR origins involved in infectious-induced systemic autoimmune diseases.

A deeper understanding of the genetic predisposition and the pathogen-derived factors responsible to exacerbate the IIR might potentially provide therapeutic targets to counteract flares in systemic autoimmune diseases.

Video abstract

http://links.lww.com/COR/A44
Validation of Simplified Chinese Version of the Pain Self-Efficacy Questionnaire (SC-PSEQ) and SC-PSEQ-2 for Patients With Nonspecific Low Back Pain in Mainland China
Authors: Yang Yilin , Yang Mingyuan , Bai Jinyi , Zhao Jian , Chen Kai , Zhou Xiaoyi , Wei Xianzhao , Li Ming
Published: May 2019

Study Design.

A prospective study.

Objective.

The aim of this study was to develop the simplified Chinese version of Pain Self-efficacy Questionnaire (PSEQ) (SC-PESQ) and PSEQ-2 (SC-PSEQ-2), and evaluate the psychometric properties of the two questionnaires in patients with nonspecific low back pain.

Summary of Background Data.

PSEQ has been cross-culturally adapted into many languages with excellent reliability and validity. Recently, the short form of PSEQ-2 was developed and exhibited satisfactory psychometric properties. However, PSEQ and PSEQ-2 has not been translated or validated in mainland China.

Methods.

The original version of PSEQ and PSEQ-2 was linguistically translated and adapted to formulate the simplified Chinese version, which was then administrated by 219 patients with low back pain, along with a set of self-report health-related instruments. Statistical analysis was performed to evaluate the psychometric properties of the SC-PESQ and SC-PSEQ-2.

Results.

Two hundred nineteen patients with nonspecific low back pain were enlisted into the analysis. The SC-PSEQ and SC-PSEQ-2 had been determined excellent internal consistency (Cronbach alpha, 0.95 and 0.83), test-retest reliability (overall ICC, 0.91 and 0.88), and sound construct validity, which were supported by moderately strong association with the criterion measures, respectively. In addition, exploratory and confirmatory factor analysis have found and confirmed one-factor solution in SC-PSEQ as hypothesized.

Conclusion.

The SC-PESQ and SC-PSEQ-2 showed satisfactory psychometric properties in Chinese population with low back pain, and could be safely utilized to evaluating the self-efficacy in clinical and research setting.

Level of Evidence: 4
Combined Pedicled Vascularized and Wedge Nonvascularized Bone Graft for Treating Scaphoid Waist Nonunion With Humpback Deformity
Authors: Huang Hui-Kuang , Wu Chin-Hsien , Wang Jung-Pan , Tu Yuan-Kun
Published: May 2019

Pedicled vascularized bone graft (VBG) is a useful method in treating the scaphoid fracture nonunion, especially when the avascular necrosis exists. Humpback deformity is an important issue that we have to correct it during the treatment. We describe a method by using combined wedge non-VBG to correct the nonunion deformity when treating scaphoid nonunion with pedicled VBG. The wedge bone graft was harvested just proximal to the 2,3 intercompartmental supraretinacular artery VBG and was used as an inlay at the volar site to correct the humpback deformity, whereas the VBG was set at the dorsal site for bone bridging and blood supply. We also present our results of 10 patients with scaphoid fracture nonunion and humpback deformity treated with this method. Bone healing was achieved and the lateral intrascaphoid angles could be improved in all the 10 patients. Functional outcomes, including the Visual Analog Pain Scale for pain during activity, grip strength, the shortened Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH), and the modified Mayo Wrist Scores, were significantly improved.
Evaluation of Nursing Practice in Patients With HIV/AIDS With the Omaha System Electronic-Based Information Program
Authors: Ornek Ozlem Koseoglu , Ardic Aysun
Published: May 2019

The Omaha System is a standardized health care terminology that has been used in many different settings for nursing care worldwide for more than 20 years. In Turkey, it has been used mainly in nursing education and research. In this context, the purpose of this study was to examine paper-based nursing care plans of inpatients with HIV/AIDS according to the Omaha System and to assess the clinical suitability of the Omaha System. The study has a descriptive-retrospective design and was carried out at the Department of Infectious Diseases and Clinical Microbiology in a hospital. The sample consisted of 30 patients with HIV/AIDS who were chosen randomly from patients hospitalized between January 2007 and April 2017. Nursing care plans were reevaluated and encoded according to the Omaha System. The five most frequently diagnosed problems were oral health (27.2%), neuromusculoskeletal function (20.2%), communicable/infectious condition (19.4%), skin condition (13.2%), and circulation (5.7%). A total of 4409 nursing interventions were applied to solve the problems, and almost 74% of the interventions were categorized in the surveillance. Among the targets, physical signs/symptoms were indicated for more than 68% (3.026). The results confirmed the clinical suitability of the Omaha System.
Reversible Conduction Failure in Chronic Immune-Mediated Sensorimotor and Autonomic Polyneuropathy
Authors: Shouman Kamal , Dhamne Megha , Li Yuebing
Published: May 2019

Reversible conduction failure (RCF) has been described in several subtypes of Guillain–Barre syndrome and is typically observed within the first 10 weeks. We describe the presence of RCF lasting for at least 9 months or longer without secondary axonal degeneration in a case of chronic sensorimotor and autonomic polyneuropathy. A 63-year-old woman presented with lower back pain, limb pain, paresthesia, and weakness after a sinus infection. She was diagnosed with mild Guillain–Barre syndrome and treated symptomatically. Four months later, she developed symptoms of dysautonomia and worsening neuropathic pain, and treatment with intravenous immunoglobulin led to significant clinical improvement. Electrodiagnostic study revealed significant improvement, manifesting as increased response amplitudes, improved conduction velocities, shortening of distal latencies, and reduction of sensory and motor response durations without temporal dispersion, thus fitting to the RCF definition. Detection of RCF may have further important implications in the evaluation and management of chronic immune-mediated polyneuropathy.