bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of the Modified Patient‐Centered Medical Home Assessment for the Comprehensive Primary Care Initiative
Authors: Poznyak Dmitriy , Peikes Deborah N. , Wakar Breanna A. , Brown Randall S. , Reid Robert J.
Published: March 2017

Objective

To describe the modified Patient‐Centered Medical Home Assessment (M‐PCMH‐A) survey module developed to track primary care practices’ care delivery approaches over time, assess whether its underlying factor structure is reliable, and produce factor scores that provide a more reliable summary measure of the practice's care delivery than would a simple average of question responses.

Data Sources/Study Setting

Survey data collected from diverse practices participating in the Comprehensive Primary Care (CPC) initiative in 2012 (n = 497) and 2014 (n = 493) and matched comparison practices in 2014 (n = 423).

Study Design

Confirmatory factor analysis.

Data Collection

Thirty‐eight questions organized in six domains: Access and Continuity of Care, Planned Care for Chronic Conditions and Preventive Care, Risk‐Stratified Care Management, Patient and Caregiver Engagement, Coordination of Care across the Medical Neighborhood, and Continuous Data‐Driven Improvement.

Principal Findings

Confirmatory factor analysis suggested using seven factors (splitting one domain into two), reassigning two questions to different domain factors, and removing one question, resulting in high reliability, construct validity, and stability in all but one factor. The seven factors together formed a single higher‐order factor summary measure. Factor scores guard against potential biases from equal weighting.

Conclusions

The M‐PCMH‐A can validly and reliably track primary care delivery across practices and over time using factors representing seven key components of care as well as an overall score. Researchers should calculate factor loadings for their specific data if possible, but average scores may be suitable if they cannot use factor analysis due to resource or sample constraints.
The Role of Medicare's Inpatient Cost‐Sharing in Medicaid Entry
Authors: Keohane Laura M. , Trivedi Amal N. , Mor Vincent
Published: March 2017

Objective

To isolate the effect of greater inpatient cost‐sharing on Medicaid entry among Medicare beneficiaries.

Data Sources

Medicare administrative data (years 2007–2010) were linked to nursing home assessments and area‐level socioeconomic indicators.

Study Design

Medicare beneficiaries who are readmitted to a hospital must pay an additional deductible ($1,100 in 2010) if their readmission occurs more than 59 days following discharge. In a regression discontinuity analysis, we take advantage of this Medicare benefit feature to test whether beneficiaries with greater cost‐sharing have higher rates of Medicaid enrollment.

Data Extraction Methods

We identified 221,248 Medicare beneficiaries with an initial hospital stay and a readmission 53–59 days later (no deductible) or 60–66 days later (charged a deductible).

Principal Findings

Among beneficiaries in low‐socioeconomic areas with two hospitalizations, those readmitted 60–66 days after discharge were 21 percent more likely to join Medicaid compared with those readmitted 53–59 days following their initial hospitalization (absolute difference in adjusted risk of Medicaid entry: 3.7 percent vs. 3.1 percent, p = .01).

Conclusions

Increasing Medicare cost‐sharing requirements may promote Medicaid enrollment among low‐income beneficiaries. Potential savings from an increased cost‐sharing in the Medicare program may be offset by increased Medicaid participation.
Breast‐conserving therapy: An alternative to optimal cosmetic outcome and comparable prognosis in synchronous bilateral breast cancer
Authors: Sejdinaj Fabjola , Yang Weige , Zhu Wei , Zhang Hongwei
Published: March 2017

Aim

Our main purpose initially was to simple retrospectively analyze the current literature for publishing and comparative studies on synchronous bilateral breast cancer (SBBC) with unilateral breast cancer (UBC) or metachronous bilateral breast cancer (MBBC) post breast‐conserving therapy BCT, and furthermore gather data on impact of bilateralism in changes of overall survival (OS), disease‐free survival (DFS) and local recurrence rate (LCC) to reach a sensible conclusion.

Patients and Methods

We conducted a Medline database search for all studies reporting on SBBC patients who underwent BCT and comparison of this entity with UBC OR MBBC. Assessment of bilateralism as a prognostic factor and estimation of its impact on DFS, LCC and OS of SBBC patients still generates many contradictions in the literature. Comparison between relatively small entities of SBBC with UBC using retrospective studies or population‐based inquiries are the primary line of research.

Results

A worst prognostic effect or a downward tendency towards increased mortality rates for simultaneous occurrence of breast carcinomas compared to UBC patients is commonly supported by many studies. Clinical experiences of many physicians and data achieved from the majority of studies have suggested that application of breast‐conversing therapy for SBBC patients, even though appears to be a challenging alternative to mastectomy and has yielded better cosmetic outcome and similar DFS and OS.

Conclusion

Although the majority of studies report a more adverse survival outcome for SBBC patients, breast‐conserving therapy is a feasible surgical choice for this group of patients, as it is a suitable alternative to mastectomy.
The relationship between high performance work systems and employee proactive behaviour: role breadth self‐efficacy and flexible role orientation as mediating mechanisms
Authors: Beltrán‐Martín Inmaculada , Bou‐Llusar Juan Carlos , Roca‐Puig Vicente , Escrig‐Tena Ana Belén
Published: March 2017

Drawing on the contextual perspective, this study provides novel empirical evidence on how the organisational context (specifically, the firm's human resource strategy) has an effect on employee proactivity. We use matched data from managers and employees in 102 Spanish professional service firms to examine how high performance work systems contribute to enhance employee proactive behaviours through two motivational variables: role breadth self‐efficacy and flexible role orientation. Results of a multilevel study demonstrate that role breadth self‐efficacy mediates between HPWS and employee proactivity, but flexible role orientation does not mediate this relationship.
Effects of Urbanization on Flow Duration and Stream Flashiness: A Case Study of Puget Sound Streams, Western Washington, USA
Authors: Rosburg Tyler T. , Nelson Peter A. , Bledsoe Brian P.
Published: March 2017

The overall influence of urbanization on how flows of different frequency might change over time, while important in hydrologic design, remains imprecisely known. In this study, we investigate the effects of urbanization on flow duration curves (FDCs) and flow variability through a case study of eight watersheds that underwent different amounts of growth, in the Puget Sound region in Western Washington State, United States. We computed annual FDCs from flow records spanning 1960‐2010 and, after accounting for the effects of precipitation, we conducted statistical trend analyses on flow metrics to quantify how key FDC percentiles changed with time in response to urbanization. In the urban watersheds, the entire FDC tended to increase in magnitude of flow, especially the 95th‐99th percentile of the daily mean flow series, which increased by an average of 43%. Stream flashiness in urban watersheds was found to increase by an average of 70%. The increases in FDC magnitude and flashiness in urbanizing watersheds are most likely a result of increasing watershed imperviousness and altered hydrologic routing. Rural watersheds were found to have decreasing FDC magnitude over the same time period, which is possibly due to anthropogenic extractions of groundwater, and increasing stream flashiness, which is likely a result of reductions in base flow and increasing precipitation intensity and variability.
Cyclic‐di‐GMP signalling meets extracellular polysaccharide synthesis in Bacillus subtilis
Authors: Kampf Jan , Stülke Jörg
Published: March 2017

In order to resist harmful environmental conditions, many bacteria form multicellular aggregates called biofilms. In these biofilms, they protect themselves in a self‐produced matrix consisting of extracellular polysaccharides, proteins and DNA. In many bacteria, biofilm formation is stimulated in the presence of the second messenger cyclic di‐GMP. In this issue of Environmental Microbiology Reports, Bedrunka and Graumann have studied matrix production by the proteins encoded in the Bacillus subtilis ydaJKLMN operon. For the first time, they were able to provide a link between c‐di‐GMP signalling and matrix production in this bacterium. The work demonstrates that the c‐di‐GMP receptor protein YdaK forms a membrane‐bound complex with the YdaM and YdaN proteins, and that this interaction with YdaK is required for polysaccharide production by YdaL, YdaM and YdaN.
Snail acetylation by histone acetyltransferase p300 in lung cancer
Authors: Chang Rui , Zhang Yinjie , Zhang Peng , Zhou Qinghua
Published: March 2017

Background

Epithelial to mesenchymal transition (EMT) is a complex and dynamic molecular event in lung cancer metastasis that has not yet been thoroughly investigated. EMT transcriptional factors, such as Snail, play a central role in regulation of the EMT process. In this study, we sought to identify an association between p300 and Snail in lung cancer, as well as the engagement of p300 in Snail acetylation.

Methods

We transfected p300 small interfering RNA into lung cancer cells to detect Snail and E‐cadherin expression levels by real time‐PCR. Immunoprecipitation assay was conducted to determine Snail acetylation in vivo. Bacteria‐expressed Snail was purified to analyze Snail acetylation in vitro. We further mutated lysine 187 for identifying acetylated residue in Snail.

Results

Snail transcription in lung cancer cells was repressed by p300 knockdown. E‐cadherin expression was increased by transfection of p300 small interfering RNA in a dose‐dependent manner. Immunoprecipitation and Western blot assay with anti‐acetylated lysine antibody were used to confirm that Snail was acetylated by p300. A sequence coding snail gene was cloned into glutathione S‐transferase‐tagged vector and the fusion protein was purified using glutathione. We observed Snail acetylation in vitro by incubation of recombinant Snail and p300 histone acetyltransferase domain with acetyl coenzyme A. The reduced Snail acetylation level was related to lysine mutation at position 187 of Snail.

Conclusion

There was a correlation between Snail and p300 expressions in lung cancer. Moreover, p300 acetylates Snail both in vivo and in vitro, and K187 may be involved in this modification.
Prevalence of Prenatal Alcohol Exposure in the State of Texas as Assessed by Phosphatidylethanol in Newborn Dried Blood Spot Specimens
Authors: Bakhireva Ludmila N. , Sharkis Janet , Shrestha Shikhar , Miranda‐Sohrabji Tristan J. , Williams Sonnie , Miranda Rajesh C.
Published: March 2017

Background

While 2 to 5% of school‐aged children in the United States are estimated to be affected by fetal alcohol spectrum disorders (FASD), the prevalence of prenatal alcohol exposure (PAE) might be substantially underreported. Our objective was to systematically estimate the prevalence of PAE in Texas by measuring a direct ethanol metabolite, phosphatidylethanol (PEth), in 1,000 infant residual dried blood spots (irDBSs) in the Texas Newborn Screening Repository.

Methods

All public health regions (PHRs) were represented proportional to their 2014 birth rate (~0.25% of total births). A cross‐sectional study design (unit of observation: individual irDBS cards/infants) with additional ecologic subanalysis (unit of observation: aggregate measures for each Texas PHR) was utilized. The study used PEth‐irDBS to estimate the prevalence of PAE within 1 month before delivery for the state of Texas and each Texas PHR. The ecologic subanalysis compared different geographical regions’ aggregate prevalence of PAE with (i) retail liquor licenses, (ii) median household income by PHR, and (iii) prevalence of birth outcomes commonly associated with FASD.

Results

The sample included an equal number of males and females; 47.8% non‐Hispanic White, 40.8% Hispanic, 6.6% African American, and 4.8% Asian infants. In the entire sample, 8.4% of irDBSs were positive for PEth (>20 ng/ml) indicative of PAE within approximately 1 month before delivery. Large regional differences were observed with mostly urban, high median‐income regions demonstrating the highest prevalence.

Conclusions

Results of this first systematic statewide PAE prevalence study demonstrate that PAE might be more prevalent than previously thought. Active case ascertainment efforts for FASD coupled with systematic objective assessment of PAE should expand to the national level to better estimate public health needs required to provide adequate services for children affected by PAE.
Accelerated orthodontic treatment ‐ what's the evidence?
Authors: Miles P
Published: March 2017

The demand and accessibility of orthodontic care has increased but has also been accompanied by patient requests for shorter treatment times. Longer orthodontic treatment increases the risk of decalcification, gingival recession, and root resorption and so shorter treatment times have multiple advantages as well as appealing to patient's desires. Numerous techniques and materials have been suggested to reduce treatment times but, in most cases, are based upon selected case reports with no prospective clinical trials to validate claims. The present review examines many of the current options purported to accelerate orthodontic tooth movement and the level of evidence presently available. There is some evidence to suggest that low‐level laser therapy and a corticotomy involving the raising of a muco‐periosteal flap are associated with accelerated orthodontic tooth movement; however, the current level of evidence is low to moderate in quality. For this reason, further research is required before routine application could be recommended.
Clear aligners in orthodontic treatment
Authors: Weir T
Published: March 2017

Since the introduction of the Tooth Positioner (TP Orthodontics) in 1944, removable appliances analogous to clear aligners have been employed for mild to moderate orthodontic tooth movements. Clear aligner therapy has been a part of orthodontic practice for decades, but has, particularly since the introduction of Invisalign appliances (Align Technology) in 1998, become an increasingly common addition to the orthodontic armamentarium. An internet search reveals at least 27 different clear aligner products currently on offer for orthodontic treatment. The present paper will highlight the increasing popularity of clear aligner appliances, as well as the clinical scope and the limitations of aligner therapy in general. Further, the paper will outline the differences between the various types of clear aligner products currently available.
The mandibular muscles in contemporary orthodontic practice: a review
Authors: Woods MG
Published: March 2017

It is widely accepted that all dentists should have a thorough understanding of the muscles involved in moving or stabilizing the mandible. However, there is still much discussion regarding the influence of the mandibular muscles on normal facial growth and dental development, as well as on orthodontic treatment and post‐treatment stability. Potential patients with different underlying vertical muscle patterns will have differences in the expected directions of future mandibular growth, lateral profile shape, facial and arch widths and vertical occlusal relationships. In turn, thorough diagnoses are likely to lead to differences in individual aims and objectives, treatment plans, timing of commencement, mechanical design, lateral profile and smile‐aesthetics outcomes, choice of retention and plans for long‐term maintenance. The potential influence of the mandibular muscles on normal morphologic variation and the soft tissue implications on contemporary orthodontic treatment and stability will be addressed in this review.
Root Resorption with Orthodontic Mechanics: Pertinent Areas Revisited
Authors: Krishnan V
Published: March 2017

Root resorption can occur at any time during orthodontic treatment and lead to a compromise in the prognosis of the tooth and the stability of the treatment results. Recent research has focused more on the cause and effect relationship as well as preventive or treatment options to combat this unwelcome event. Investigations have highlighted the genetic as well as molecular aspects of the process and enabled clinicians to determine which patients might be susceptible. A proper medical history, an assessment of predisposing factors, a radiographic evaluation for alterations in root morphology and careful planning and execution of orthodontic mechanics may reduce the incidence of root resorption. The current review is aimed at providing clinicians and academics with an insight into the process of root resorption, the methods of identification during its early stages and intervention at the right time to reduce its severity.
Vitamin D, bones and muscle: myth versus reality
Authors: Duque Gustavo , Daly Robin M. , Sanders Kerrie , Kiel Douglas P.
Published: March 2017

Objectives

Evidence regarding the efficacy and dosing of vitamin D on fall and fracture prevention, with or without calcium, is characterised by uncertainty.

Methods

A panel of experts was organised at the First Australasian Conference on Sarcopenia and Frailty in Melbourne, Australia, in November 2016 to provide an interpretation of the current evidence and to give their opinions regarding the supplementation of vitamin D in three hypothetical cases.

Results and Conclusion

The authors conclude that (i) target serum 25(OH)D concentration should be 50 to 60 nmol/L year round, with a conservative upper limit <100 nmol/L; (ii) change in serum concentrations at any given dose is highly variable among individuals; (iii) dosing interval may need to be <2 months to have a continuous benefit; (iv) a loading dose can raise levels to target quickly, but there is no evidence yet that this has any positive effect on falls or fracture outcomes; and (v) a maintenance dose of 1000 IU/day, or given as an equivalent dose weekly or monthly, is sufficient for most individuals.
Successful use of Bruton's kinase inhibitor, ibrutinib, to control paraneoplastic pemphigus in a patient with paraneoplastic autoimmune multiorgan syndrome and chronic lymphocytic leukaemia
Authors: Lee Andrew , Sandhu Suneet , Imlay‐Gillespie Louise , Mulligan Stephen , Shumack Stephen
Published: March 2017

We present the case of a 51‐year‐old man who developed paraneoplastic pemphigus (PNP) in the context of chronic lymphocytic leukemia (CLL). His CLL was successfully controlled with ibrutinib. Concurrently, there was significant improvement of his PNP, suggesting that ibrutinib may be a very useful addition to the treatment options in this potentially life‐threatening autoimmune disorder.
Type I interferons modulate methotrexate resistance in gestational trophoblastic neoplasia
Authors: Elias Kevin M. , Harvey Richard A. , Hasselblatt Kathleen T. , Seckl Michael J. , Berkowitz Ross S.
Published: March 2017

Problem

Resistance to methotrexate is a leading clinical problem in gestational trophoblastic neoplasia (GTN), but there are limited laboratory models for this condition.

Method of study

We created isogenic trophoblastic cell lines resistant to methotrexate and compared these to the parent cell lines using gene expression microarrays and qRT‐PCR followed by mechanistic studies using recombinant cytokines, pathway inhibitors, and patient sera.

Results

Gene expression microarrays and focused analysis by qRT‐PCR revealed methotrexate led to type I interferon upregulation, in particular interferon alpha 2 (IFNA2), and methotrexate resistance was associated with chronic low level increases in type I interferon expression. Recombinant IFNA2 imparted chemosensitive choriocarcinoma cells with partial resistance to methotrexate, while chemoresistant choriocarcinoma cells were uniquely sensitive to fludarabine, a STAT1 inhibitor. In pre‐treatment patient sera, IFNA2 levels correlated with subsequent resistance to methotrexate chemotherapy.

Conclusion

Methotrexate resistance is influenced by type I interferon signaling with prognostic and therapeutic implications for treating women with GTN.
Predictors of mode of birth and duration of labour following induction using prostaglandin vaginal gel
Authors: Beckmann Michael , Gibbons Kristen , Flenady Vicki , Kumar Sailesh
Published: March 2017

Background and aims

Using data from a randomised controlled trial (RCT) comparing two policies of prostaglandin (PGE2) vaginal gel induction of labour (IOL) at term, this study aimed to determine: (i) demographic/clinical factors that predict IOL outcomes; and (ii) clinical characteristic(s) of women who would benefit from a policy of amniotomy once technically possible as opposed to giving more PGE2.

Material and methods

Following an initial PGE2 dose, women were randomised to amniotomy or repeat‐PGE2. Using RCT data, two multivariate models were developed, assessing the relationship between demographic/clinical characteristics and the outcomes of caesarean section (CS), and vaginal delivery within 24 h (VD < 24 h). Regression‐equations were used to predict the likelihood of CS and VD < 24 h, varying independent predictors from the multivariate analyses.

Results

Of 245 term women undergoing IOL, 90 had a CS, 155 delivered vaginally and 79 had a VD < 24 h. Controlling for confounders, nulliparity [adjusted odds ratio (aOR) = 3.71 (1.55, 8.88)] and modified Bishop's score (MBS) at first review [aOR = 0.78 (0.66, 0.92)] were independently associated with CS. Nulliparity [aOR = 0.06 (0.02, 0.15)], MBS at first review [aOR = 1.66 (1.35, 2.05)], and a policy of early amniotomy [aOR = 2.28 (1.04, 5.00)] were associated with VD < 24 h. Modelling using regression equations, and varying both MBS at first review and parity, there was no scenario where repeat PGE2 was predicted to be superior to an earlier amniotomy.

Conclusions

Following IOL using PGE2 vaginal gel at term, both parity and cervical favourability at first review are associated with CS and VD < 24 h. All combinations of parity and MBS at first review predicted fewer CS and greater likelihood of VD < 24 h with a policy of amniotomy once technically possible.
Guidelines in lower‐middle income countries
Authors: Olayemi Edeghonghon , Asare Eugenia V. , Benneh‐Akwasi Kuma Amma A.
Published: March 2017

Guidelines include recommendations intended to optimize patient care; used appropriately, they make healthcare consistent and efficient. In most lower‐middle income countries (LMICs), there is a paucity of well‐designed guidelines; as a result, healthcare workers depend on guidelines developed in Higher Income Countries (HICs). However, local guidelines are more likely to be implemented because they are applicable to the specific environment; and consider factors such as availability of resources, specialized skills and local culture. If guidelines developed in HICs are to be implemented in LMICs, developers need to incorporate local experts in their development. Involvement of local stakeholders may improve the rates of implementation by identifying and removing barriers to implementation in LMICs. Another option is to encourage local experts to adapt them for use in LMICs; these guidelines may recommend strategies different from those used in HICs, but will be aimed at achieving the best practicable standard of care. Infrastructural deficits in LMICs could be improved by learning from and building on the successful response to the human immunodeficiency virus/acquired immunodeficiency syndrome pandemic through interactions between HICs and LMICs. Similarly, collaborations between postgraduate medical colleges in both HICs and LMICs may help specialist doctors training in LMICs develop skills required for guideline development and implementation.
The practice and perception of precautionary allergen labelling by the Australasian food manufacturing industry
Authors: Zurzolo G. A. , Peters R. L. , Koplin J. J. , de Courten M. , Mathai M. L. , Tye‐Din J. A. , Tang M. L. K. , Campbell D. E. , Ponsonby A‐L. , Prescott S. L. , Gurrin L. , Dharmage S.C. , Allen K. J.
Published: March 2017

Background

The precautionary allergen labelling (PAL) and Voluntary Incidental Trace Allergen Labelling (VITAL®) tools were designed by industry to assist consumers with selecting safe foods for consumption. However, a sizeable proportion of food products bear no label, and it is unclear whether these products are free from allergens and therefore safe to consume or have simply not undergone a risk assessment and therefore remain unlabelled for that reason.

Objective

To assess the prevalence of unlabelled products that have undergone a risk assessment process and to examine the factors influencing industry's uptake of the VITAL® process.

Methods

A web‐based questionnaire was distributed to Australasian food and grocery manufacturers.

Results

One hundred and thirty‐seven Australasian manufacturers were contacted, and 59 questionnaires were returned (response rate: 43%). The respondents represented 454 different manufacturing sites. Manufacturers reported that 23% (95% CI 19‐28) of products (n=102/434) that had been through the VITAL® risk assessment process had no PAL statement on the label. 34% (95% CI 30‐38), (n=204/600) of products that had undergone another (non‐VITAL®) risk assessment process had no PAL statement. In examining the factors that influenced industry's uptake of the VITAL® process, 25 manufacturers reported on factors that influenced the uptake of the VITAL® process, 76% (CI 95% 55‐91) reported that VITAL® was an effective tool because it was based on science; 52% (CI 95% 31‐72) reported that it was too time‐consuming and 36% (CI 95% 18‐57) identified a concern with it not being endorsed by the government.

Conclusion and Clinical Relevance

Currently, we estimate that at least 30% of products may have been through a risk assessment process and yet bear no PAL statement on the label. Permissive labelling could be incorporated onto these products if they have been assessed to be safe for consumption.
Nadroparin carries a potentially high risk of inducing cutaneous delayed‐type hypersensitivity responses
Authors: Schindewolf Marc , Recke Andreas , Zillikens Detlef , Lindhoff‐Last Edelgard , Ludwig Ralf J.
Published: March 2017

Background

Heparins are widely used for the prophylaxis/treatment of thromboembolic events. As adverse effects, heparin‐induced skin lesions occur frequently (in 7.5–39% of patients). Skin lesions may be the only clinical manifestation of life‐threatening immune‐mediated heparin‐induced thrombocytopenia, but are commonly caused by a delayed‐type hypersensitivity response [heparin‐induced delayed‐type hypersensitivity (HIHS)]. Risk factors have not been prospectively identified.

Objectives

To identify possible risk factors for heparin‐induced skin lesions from three independent clinical trials in a combined analysis.

Methods

A pooled analysis from prospective studies was performed, and possible risk factors were included in a multiple logistic regression analysis.

Results

Obesity (body mass index of > 25), prolonged anticoagulant therapy, prior heparin exposure and younger age (< 55 years) were confirmed as independent risk factors for HIHS. The choice of anticoagulant preparation had the greatest influence. On comparison of dalteparin, enoxaparin, fondaparinux, unfractionated heparin, and nadroparin, the latter was associated with the highest risk of eliciting HIHS (odds ratio of 30.2, 95%CI: 11.7–77.9).

Conclusions

The high risk associated with nadroparin has been validated in controlled trials, and this emphasizes the singularity of each heparin preparation in terms of allergenicity and that individualized anticoagulation is required.
Further Tests of a Dynamic‐Adjustment Account of Saccade Targeting During the Reading of Chinese
Authors: Liu Yanping , Huang Ren , Gao Dingguo , Reichle Erik D.
Published: March 2017

There are two accounts of how readers of unspaced writing systems (e.g., Chinese) know where to move their eyes: (a) saccades are directed toward default targets (e.g., centers of words that have been segmented in the parafovea); or (b) saccade lengths are adjusted dynamically, as a function of ongoing parafoveal processing. This article reports an eye‐movement experiment supporting the latter hypothesis by demonstrating that the slope of the relationship between the saccade launch site on word N and the subsequent fixation landing site on word N + 1 is > 1, suggesting that saccades are lengthened from launch sites that afford more parafoveal processing. This conclusion is then evaluated and confirmed via simulations using implementations of both hypotheses (Liu, Reichle, & Li, 2016), with a discussion of these results for our understanding of saccadic targeting during reading and existing models of eye‐movement control.
Decolorisation by Bacillus flexus of exhausted dyebaths containing CI Acid Red 249 and their reuse for wool dyeing
Authors: Parmar Neha D. , Shukla Sanjeev R.
Published: March 2017

A dyebath containing left‐over CI Acid Red 249 after dyeing of wool was completely decolorised using an isolated bacteria Bacillus flexus. Optimisation was carried out by varying the pH, temperature, dye concentration, and microbial loading. Complete decolorisation of a 50 mg l−1 dye solution was achieved in 8 h at pH 7 and 37 °C with 10% v/v loading of the bacteria. The decolorised bath was utilised for dyeing of wool fabric with the same dye at 5% shade. This cycle of dyeing–decolorising–dyeing was repeated 5 times. The evaluation of dyed fabric was done using K/S, colour values, and fastness to light and washing. Comparison of a sample dyed with the conventional exhaust process showed that the dyeing quality is not affected for all five successive reuse cycles. The results are important from the viewpoint of reducing water consumption and chemicals.
A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans
Authors: Ryu S , Park S , Lee JH , Kim YR , Na HS , Lim HS , Choi HY , Hwang IY , Lee JG , Park ZW , Oh WY , Kim JM , Choi SE
Published: March 2017

We performed a double‐blinded, genotype‐based stratification study to explore the pharmacokinetics and pharmacodynamics of amitriptyline according to CYP2C19 and CYP2D6 genotype in Korean subjects. Twenty‐four healthy adults were grouped by genotype of CYP2C19 and CYP2D6. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of N‐demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of CYP2C19. The extent of hydroxylation of amitriptyline or nortriptyline was significantly reduced in subjects carrying two CYP2D6 decreased functional alleles compared with those with no or one decreased functional allele. The overall metabolic pathway of amitriptyline was more likely to be dominated by CYP2C19 than CYP2D6. The gene variations of CYP2C19 and CYP2D6 did not change the pharmacodynamic effect. The findings of this study will provide useful information on individualized drug treatment with amitriptyline considering both CYP2D6 and CYP2C19 gene variations.
Alcohol consumption by breastfeeding mothers: Frequency, correlates and infant outcomes
Authors: Wilson Judy , Tay Rui Yang , McCormack Clare , Allsop Steve , Najman Jake , Burns Lucy , Olsson Craig A. , Elliott Elizabeth , Jacobs Sue , Mattick Richard P. , Hutchinson Delyse
Published: March 2017

Introduction and Aims

There is limited research regarding the effects of alcohol consumption by breastfeeding mothers on infant development. This study examined the frequency, correlates and outcomes of alcohol use during lactation.

Design and Methods

Data were from an Australian cohort study. Maternal demographics and substance use were assessed during pregnancy and at 8 weeks and 12 months postpartum. Breastfeeding duration, infant feeding, sleeping and development (Ages and Stages Questionnaire) were also assessed postpartum. Logistic regression and general linear model analyses examined characteristics of women who drank during breastfeeding, and the association between alcohol use during breastfeeding and infant outcomes.

Results

Alcohol use was reported by 60.7% and 69.6% of breastfeeding women at 8 weeks and 12 months postpartum, respectively. Breastfeeding women who consumed alcohol were more likely to be born in Australia or another English‐speaking country, be tertiary educated and have higher household incomes. Most drank at low levels (≤14 standard drinks per week, <3 per occasion) and employed strategies (e.g. timing of alcohol use) to minimise alcohol passed onto infants via breastmilk. Alcohol consumption was unrelated to breastfeeding duration, infant feeding and sleeping behaviour at 8 weeks, and most infant developmental outcomes at 8 weeks or 12 months, after adjusting for confounders. The only significant association showed that infants whose mothers drank at 8 weeks postpartum had more favourable results for personal‐social development at 12 months compared with those whose mothers abstained.

Discussion and Conclusions

Low level drinking during breastfeeding is not linked with shorter breastfeeding duration or adverse outcomes in infants up to 12 months of age. [Wilson J, Tay RY, McCormack C, Allsop S, Najman J, Burns L, Olsson CA, Elliott E, Jacobs S, Mattick RP, Hutchinson D. Alcohol consumption by breastfeeding mothers: Frequency, correlates and infant outcomes. Drug Alcohol Rev 2017;00:000‐000]
Health service utilisation attributable to methamphetamine use in Australia: Patterns, predictors and national impact
Authors: McKetin Rebecca , Degenhardt Louisa , Shanahan Marian , Baker Amanda L. , Lee Nicole K. , Lubman Dan I.
Published: March 2017

Aim and background. We estimated health service utilisation attributable to methamphetamine use, its national impact and examined other predictors of health service utilisation among dependent methamphetamine users. Method. Past year rates of health service utilisation (number of attendances for general hospitals, psychiatric hospitals, emergency departments, general practitioners, psychiatrists, counsellors or psychologists, and dentists) were estimated for three levels of methamphetamine use (no use, < weekly, ≥ weekly) using panel data from a longitudinal cohort of 484 dependent methamphetamine users from Sydney and Brisbane, Australia. Marginal rates for methamphetamine use were multiplied by 2013 prevalence estimates from the National Drug Strategy Household Survey. Covariates included other substance use, demographics, mental disorders and drug treatment. Findings. Health service use was high. More frequent methamphetamine use was associated with more frequent presentations to emergency departments (incidence rate ratios 1.3–2.1) and psychiatric hospitals (incidence rate ratios 5.3–8.3) and fewer presentations to general practitioners, dentists and counsellors. We estimate methamphetamine use accounted for between 28 400 and 80 900 additional psychiatric hospital admissions and 29 700 and 151 800 additional emergency department presentations in 2013. More frequent presentations to these services were also associated with alcohol and opioid use, comorbid mental health disorders, unemployment, unstable housing, attending drug treatment, low income and lower education. Conclusions. Frequent methamphetamine use has a significant impact on emergency medical and psychiatric services. Better provision of non‐acute health care services to address the multiple health and social needs of dependent methamphetamine users may reduce the burden on these acute care services. [McKetin R, Degenhardt L, Shanahan M, Baker AL, Lee NK, Lubman DI. Health service utilisation attributable to methamphetamine use in Australia: patterns, predictors and national impact. Drug Alcohol Rev 2017;00:000–000]
Mapping language to the world: the role of iconicity in the sign language input
Authors: Perniss Pamela , Lu Jenny C. , Morgan Gary , Vigliocco Gabriella
Published: March 2017

Most research on the mechanisms underlying referential mapping has assumed that learning occurs in ostensive contexts, where label and referent co‐occur, and that form and meaning are linked by arbitrary convention alone. In the present study, we focus on iconicity in language, that is, resemblance relationships between form and meaning, and on non‐ostensive contexts, where label and referent do not co‐occur. We approach the question of language learning from the perspective of the language input. Specifically, we look at child‐directed language (CDL) in British Sign Language (BSL), a language rich in iconicity due to the affordances of the visual modality. We ask whether child‐directed signing exploits iconicity in the language by highlighting the similarity mapping between form and referent. We find that CDL modifications occur more often with iconic signs than with non‐iconic signs. Crucially, for iconic signs, modifications are more frequent in non‐ostensive contexts than in ostensive contexts. Furthermore, we find that pointing dominates in ostensive contexts, and suggest that caregivers adjust the semiotic resources recruited in CDL to context. These findings offer first evidence for a role of iconicity in the language input and suggest that iconicity may be involved in referential mapping and language learning, particularly in non‐ostensive contexts.
Placebo‐controlled, randomized trial of the addition of once‐weekly glucagon‐like peptide‐1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD‐9)
Authors: Pozzilli Paolo , Norwood Paul , Jódar Esteban , Davies Melanie J. , Ivanyi Tibor , Jiang Honghua , Woodward D. Bradley , Milicevic Zvonko
Published: March 2017

Aim

To compare the addition of weekly dulaglutide vs the addition of placebo to titrated glargine in patients with type 2 diabetes (T2D) with sub‐optimum glycated haemoglobin (HbA1c) concentration.

Materials and Methods

Patients (N = 300) from this phase III, double‐blind, parallel‐arm, placebo‐controlled study were randomized to weekly subcutaneous injections of dulaglutide 1.5 mg or placebo with titrated daily glargine (mean ± standard deviation baseline dose: 39 ± 22 U), with or without metformin (≥1500 mg/d). The primary endpoint was superiority of dulaglutide/glargine to placebo/glargine with regard to change from baseline in HbA1c level at 28 weeks.

Results

Least squares (LS) mean ± standard error (s.e.) HbA1c changes from baseline were −1.44 ± 0.09% (−15.74 ± 0.98 mmol/mol) with dulaglutide/glargine and −0.67 ± 0.09% (−7.32 ± 0.98 mmol/mol) with placebo/glargine at 28 weeks (LS mean difference [95% confidence interval] −0.77% [−0.97, −0.56]; P < .001). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: −2.41 ± 0.39 kg; P < .001). Increases from baseline in mean glargine dose were significantly smaller with dulaglutide/glargine vs placebo/glargine (13 ± 2 U [0.1 ± 0.02 U/kg] vs 26 ± 2 U [0.3 ± 0.02 U/kg], respectively; P < .001; LS mean ± s.e. final dose: dulaglutide/glargine, 51 ± 2 U; placebo/glargine, 65 ± 2 U). The hypoglycaemia rate (≤3.9 mmol/L threshold) was 7.69 ± 15.15 and 8.56 ± 16.13 events/patient/year, respectively (P = .488). One episode of severe hypoglycaemia occurred in the dulaglutide/glargine group. Common gastrointestinal adverse events with dulaglutide were nausea (12.0%), diarrhoea (11.3%) and vomiting (6.0%).

Conclusions

Weekly dulaglutide 1.5 mg added to basal insulin is an efficacious and well tolerated treatment option for patients with T2D.
Insulin degludec: Lower day‐to‐day and within‐day variability in pharmacodynamic response compared with insulin glargine 300 U/mL in type 1 diabetes
Authors: Heise Tim , Nørskov Marianne , Nosek Leszek , Kaplan Kadriye , Famulla Susanne , Haahr Hanne L.
Published: March 2017

Aim

To compare day‐to‐day and within‐day variability in glucose‐lowering effect between insulin degludec (IDeg) and insulin glargine 300 U/mL (IGlar‐U300) in type 1 diabetes.

Materials and methods

In this double‐blind, crossover study, patients were randomly assigned to 0.4 U/kg of IDeg or IGlar‐U300 once daily for two treatment periods lasting 12 days each. Pharmacodynamic variables were assessed at steady‐state from the glucose infusion rate profiles of three 24‐hour euglycaemic glucose clamps (days 6, 9 and 12) during each treatment period.

Results

Overall, 57 patients completed both treatment periods (342 clamps). The potency of IGlar‐U300 was 30% lower than IDeg (estimated ratio 0.70, 95% confidence interval [CI] 0.61; 0.80;
P
 < .0001). The distribution of glucose‐lowering effect was stable across 6‐hour intervals (24%‐26%) for IDeg, while IGlar‐U300 had greater effects in the first (35%) and last (28%) intervals compared with 6 to 12 hours (20%) and 12 to 18 hours (17%). Within‐day variability (relative fluctuation) was 37% lower with IDeg than with IGlar‐U300 (estimated ratio IDeg/IGlar‐U300: 0.63, 95% CI 0.54; 0.73;
P
 < .0001). The day‐to‐day variability in glucose‐lowering effect with IDeg was approximately 4 times lower than IGlar‐U300 (variance ratio IGlar‐U300/IDeg: 3.70, 95% CI 2.42; 5.67;
P
 < .0001). The day‐to‐day variability in glucose‐lowering effect assessed in 2‐hour intervals was consistently low with IDeg over 24 hours, but steadily increased with IGlar‐U300 to a maximum at 10 to 12 hours and 12 to 14 hours after dosing (variance ratios 12.4 and 11.4, respectively).

Conclusion

IDeg has lower day‐to‐day and within‐day variability than IGlar‐U300 and a more stable glucose‐lowering effect, which might facilitate titration and enable tighter glycaemic control with a reduced risk of hypoglycaemia.
Case report and review of nonischemic spontaneous papillary muscle rupture reports between 2000 and 2015
Authors: Gouda Pishoy , Weilovitch Lisa , Kanani Ronak , Har Bryan
Published: March 2017

Spontaneous papillary muscle rupture (PMR) is a rare cardiovascular emergency. We present a 63‐year‐old male who presents with acute dyspnea who was found to have an anterior PMR, with no evidence of coronary artery disease, infection, or trauma. A review of cases of nonischemic spontaneous PMR published in 2000–2015 identified 11 additional cases of spontaneous PMR. Posterior and anterior papillary muscles involvement was identified in 54.5% and 45.5% of cases, respectively. Rapid identification due to advances in imaging modalities and improved surgical management has led to optimal outcomes in patients with spontaneous PMR.
A giant aneurysm of noncoronary sinus of Valsalva concomitant with aortic regurgitation and mitral regurgitation
Authors: Luo Yi , Fang Zhi , Meng Wei
Published: March 2017

Aneurysms of the sinus of Valsalva (ASV) are rare, with an incidence ranging from 0.1% to 3.5% of all congenital cardiac defects and a prevalence of 0.009% in an autopsy series.ASVs occur much more frequently in the right coronary sinus of Valsalva. Previous reports, based on necropsy and cardiac surgery findings, estimated that 20% of ASVs are unruptured. Patients with an unruptured ASV may remain asymptomatic for a long period of time until rupture. They may also presented with dyspnea, palpitation, and angina‐like chest pain. Aortic insufficiency in the patients with unruptured ASVs is common, and other valvular lesions can be observed in these patients as well. Echocardiography, as a noninvasive and portable tool, is widely used to detect ASVs. Additionally, computed tomography and cardiac magnetic resonance imaging, alone or in combination, can provide precise information about its anatomic extension and intrinsic characteristics of the pathology.
Characterization of left ventricle energy loss in healthy adults using vector flow mapping: Preliminary results
Authors: Xu Lei , Sun Chao , Zhu Xiaoli , Liu Weihua , Ta Shengjun , Zhao Dan , Wang Feifei , Liu Liwen
Published: March 2017

Background

Energy loss (EL) is a new quantitative hemodynamic index based on vector flow mapping (VFM). This study aimed to characterize EL of the left ventricle (LV) in healthy adults.

Methods

Fifty‐one healthy adults were enrolled in this study. EL of LV was analyzed frame by frame using color Doppler images of a standard apical three‐chamber dynamic view on an offline VFM workstation. The average EL of systole and diastole was calculated, and the results were averaged over three cardiac cycles.

Results

The average EL for systole and diastole was 11.07±5.82J/m/s and 11.58±5.54 J/m/s, respectively. Multivariate regression analysis showed that the aortic velocity time integral (AOVTI), A‐wave peak velocity, and isovolumetric contraction time (IVCT) were independently associated with the average systolic EL. E‐wave peak velocity, height, and IVCT were independently associated with the average diastolic EL. For females, the average systolic and diastolic EL was 12.66±7.06J/m/s and 13.90±5.37J/m/s, respectively. For males, the systolic and diastolic EL was 9.29±3.33J/m/s and 8.97±4.55J/m/s, respectively.

Conclusions

Energy loss in LV changes regularly during the cardiac cycle. The average systolic EL has a high positive correlation with AOVTI, whereas the average diastolic EL has with E‐wave peak velocity. Women have higher average EL than men in both systole and diastole. By recognizing the EL characterization of healthy adults, the variation in EL may reflect cardiac dysfunction. These were preliminary results, and thus, the clinical implications of EL warrant further investigation.
Host‐associated differentiation in a pecan and water hickory Aphidomorpha community
Authors: Medina R.F. , Dickey A.M. , Harrison K. , Miller G.L.
Published: March 2017

Host‐associated differentiation (HAD) is the formation of genetically distinct, host‐associated populations created and maintained by ecologically mediated reproductive isolation. HAD potentially accounts for species origins in parasites, including herbivorous insects. Although case studies testing the occurrence of HAD are accumulating, it is still unclear how common HAD is and which specific ecological traits explain its occurrence. To address these issues, studies are needed that include negative results (i.e., instances in which parasite populations do not exhibit HAD) and test for HAD across communities (i.e., several parasite species on the same set of host species). In this study, HAD was tested in a community of six species of Aphidomorpha (Hemiptera) that share a host‐plant pair: pecan [Carya illinoinensis (Wangenh.) K.Koch] and water hickory [Carya aquatica (F.Michx) Nutt., both Juglandaceae] trees. All six species are parthenogenetic and three species are endophagous, traits that can exacerbate host‐specific selection. AFLP markers were employed to detect the presence of genetically distinct, host‐associated populations for each insect species. Strict HAD (i.e., the occurrence of genetically distinct pecan‐associated and water hickory‐associated genotypes) was found in Phylloxera notabilis Pergande (Phylloxeridae), Phylloxera devastatrix Pergande, and Monelliopsis pecanis Bissel (Aphididae). Monellia caryella Fitch (Aphididae) displayed a pattern of partial HAD (i.e., the occurrence of only a genetically distinct pecan‐associated genotype). No HAD was found in Melanocallis caryaefoliae Davis (Aphididae) or Phylloxera texana Stoetzel. The pattern of HAD occurrence in the pecan and water hickory Aphidomorpha community indicated that neither parthenogenesis nor endophagy sufficiently explain the occurrence of HAD in this system.