bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of spermatogenic variation in a polymorphic lizard, Sceloporus aeneus (Squamata: Phrynosomatidae)
Authors: Hernández‐Gallegos Oswaldo , Granados‐González Gisela , Rheubert Justin L. , Villagrán‐SantaCruz Maricela , Peña‐Herrera Eric , Gribbins Kevin M.
Published: May 2018

Although different mechanisms exist to explain the presence of polymorphism in lizards, one model suggests that multiple morphotypes display the same level of fitness. Three male morphs (grey, yellow and orange) coexist in Sceloporus aeneus, a Mexican endemic oviparous lizard. Using a histological perspective, we test the hypothesis that spermatogenic output does not vary across morphotypes of S. aeneus during its maximum testicular activity. Males of S. aeneus (five grey, five yellow and five orange) were collected in Calimaya, Estado de México, Mexico. Snout‐vent length (SVL), testis mass, diameter and epithelial heights for the seminiferous tubules and epididymis, and the number of layers of germ cells did not vary among morphs; moreover, according to principal component analysis, a high overlap among lateral colour morphs exists. Our results suggest strongly that the lateral colour morphs in S. aeneus have the same spermatogenic output, and natural selection may be a stronger driving force than sexual selection within this species. Further studies into other lizard species with multiple morphotypes are required to determine whether the lack of variation in spermatogenic output observed in this endemic lizard is consistent across polymorphic species which will provide a greater understanding of the selective mechanisms acting on an individual’s fitness.
Pharmacokinetics, Pharmacodynamics and Safety of a Single Dose of Imarikiren, a Novel Renin Inhibitor, in Healthy Male Subjects
Authors: Matsuno Kumi , Kuroda Shingo , Tanaka Shingo , Nakamichi Hiroyuki , Kagawa Tomoya , Koumura Emiko
Published: May 2018

Imarikiren hydrochloride (TAK‐272/SCO‐272) is a novel direct renin inhibitor with potential indications for cardiovascular and renal diseases. This phase I study evaluated the pharmacokinetics, pharmacodynamics and safety of a single oral administration of imarikiren in healthy Japanese male subjects. The Dose‐Ascending part (double‐blind, placebo‐controlled, parallel‐group design; n = 60) comprised six steps from 5 to 200 mg (n = 8 for imarikiren and n = 2 for placebo per step). The Food Effect part (n = 12) was an open‐label, 2 × 2 crossover design with a dose of 50 mg to evaluate the effect of food on the pharmacokinetics and safety of imarikiren. There was a generally linear relationship between dose and area under the plasma concentration–time curve (0 to infinity) or maximum plasma concentration of imarikiren. Food had no clinically significant effect on the exposure of imarikiren. Inhibition of plasma renin activity was rapid and lasted up to 24 hr at all doses. Plasma active renin concentration increased, reaching a maximum at approximately 6 hr, in a nearly dose‐dependent manner. Across both study parts, the number of subjects with treatment‐emergent adverse events ranged from 0 to 3 per group with no dependency on dose. All treatment‐emergent adverse events except two were mild in intensity; there were no serious adverse events or deaths. Single oral administration of imarikiren from 5 to 200 mg was safe and well tolerated. These findings suggest that further clinical development of a once‐daily imarikiren regimen is warranted.
Reappraisal of nodal Epstein‐Barr Virus‐negative cytotoxic T‐cell lymphoma: Identification of indolent CD5+ diseases
Authors: Yamashita Daisuke , Shimada Kazuyuki , Takata Katsuyoshi , Miyata‐Takata Tomoko , Kohno Kei , Satou Akira , Sakakibara Ayako , Nakamura Shigeo , Asano Naoko , Kato Seiichi
Published: May 2018

Nodal cytotoxic molecule (CM)‐positive peripheral T‐cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein‐Barr virus (EBV)‐negative CTL to 48 patients with EBV‐positive CTL. The two groups did not differ in histopathology, T‐cell receptor (TCR) expression or rearrangement incidences, or survival curves. However, patients with EBV‐negative CTL less frequently showed hepatic involvement (P = .007), B symptoms (P = .020), hemophagocytosis (P = .024), and detectable CD4 (P = .002) and CD5 (P = .009). Univariate and multivariate analyses identified three factors that independently predicted favorable survival, onset age <60 years (P = .002), CD5 expression (P = .002), and mixed morphology (P = .013), TCRαβ was not an independent predictor (P = .30), but was strongly linked with long survivorship among patients younger than 60 years old. A prognostic model incorporating these factors worked well for prognostic delineation, independently of the International Prognostic Index (P = .007 vs P = .082) and Prognostic Index for PTCL (P = .020 vs P = .15). Moreover, this constellation of findings indicated two nodal indolent diseases: CD5+TCRαβ (n = 13), and CD5+ NK‐cell type lacking TCR expression or clonal TCRγ rearrangement (n = 4). The survival curves for these two groups were significantly superior to others (n = 29, P < .001). These diseases appear to be unique in their indolent clinical behavior, and should be managed differently from other diseases.
CXCR4‐mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA‐613
Authors: Zhu Yong , Tang Lanhua , Zhao Shushan , Sun Buhua , Cheng Liang , Tang Yifu , Luo Zhongwei , Lin Zhangyuan , Zhu Jianxi , Zhu Weihong , Zhao Ruibo , Lu Bangbao , Long Haitao
Published: May 2018

Osteosarcoma is the most common primary bone malignancy. Recently, studies showed chemokine receptor 4 (CXCR4) played a critical role in osteosarcoma. However, the regulation of CXCR4 is not fully understood. microRNAs are short, non‐coding RNAs that play an important roles in post‐transcriptional regulation of gene expression in a variety of diseases including osteosarcoma. miR‐613 is a newly discovered miRNA and has been reported to function as a tumor suppressor in many cancers. In this study, we confirmed that both Stromal Cell‐Derived Factor (SDF‐1) and CXCR4 could be prognostic markers for osteosarcoma. Meanwhile this study found that SDF‐1/CXCR4 pathway regulated osteosarcoma cells proliferation, migration and reduced apoptosis. Besides, we demonstrated that miR‐613 was significantly downregulated in osteosarcoma patients. Elevated expression of miR‐613 directly suppressed CXCR4 expression and then decreased the proliferation, migration and induced apoptosis of osteosarcoma cells. Moreover, our study found that CXCR4 promoted the development of lung metastases and inhibition of CXCR4 by miR‐613 reduced lung metastases. These data indicated that CXCR4 mediated osteosarcoma cell growth and lung metastases and this effect can be suppressed by miR‐613 through directly downregulating CXCR4.
Human T‐cell lymphotropic/leukemia virus type 1 (HTLV‐1) Tax‐specific T‐cell exhaustion in HTLV‐1‐infected individuals
Authors: Masaki Ayako , Ishida Takashi , Suzuki Susumu , Ito Asahi , Narita Tomoko , Kinoshita Shiori , Ri Masaki , Kusumoto Shigeru , Komatsu Hirokazu , Inagaki Hiroshi , Ueda Ryuzo , Iida Shinsuke
Published: May 2018

Adult T‐cell leukemia/lymphoma (ATL) is caused by Human T‐cell lymphotropic/leukemia virus type 1 (HTLV‐1), and a higher HTLV‐1 provirus load in PBMC is a risk factor for ATL development. Here, we document a significant inverse correlation between the function of HTLV‐1 Tax‐specific CTL (Tax‐CTL), as assessed by ex vivo cytokine production in response to cognate peptide, and the HTLV‐1 provirus load in PBMC in both HTLV‐1 asymptomatic carriers (AC) (Spearman rank correlation coefficient [Rs] = −0.494, P = .037, n = 18) and ATL patients (Rs = −0.774, P = .001, n = 15). There was also a significant correlation between the HTLV‐1 provirus load and the percentage of PD‐1‐positive Tax‐CTL in both HTLV‐1 AC (Rs = 0.574, P = .013) and ATL patients (Rs = 0.676, P = .006). Furthermore, the percentage of PD‐1‐positive Tax‐CTL was inversely correlated with their function in HTLV‐1 AC (Rs = −0.542, P = .020), and ATL patients (Rs = −0.639, P = .010). These findings indicate that the function of Tax‐CTL decreased as their programmed cell death protein 1 (PD‐1) levels increased, parallel to the increased HTLV‐1 provirus load in PBMC. We propose that functional Tax‐CTL are crucial for determining the HTLV‐1 provirus load in PBMC, not only in HTLV‐1 AC, but also in ATL, and that PD‐1 expression levels are reliable markers of Tax‐CTL function. Thus, modulating the immunological equilibrium between Tax‐CTL and HTLV‐1‐infected cells to achieve dominance of functional effectors could represent an ideal strategy for controlling HTLV‐1‐associated disease.
Mild subclinical hypothyroidism is associated with paediatric dyslipidaemia
Authors: Dahl Amanda R. , Iqbal Anoop Mohamed , Lteif Aida N. , Pittock Siobhan T. , Tebben Peter J. , Kumar Seema
Published: May 2018

Background

There is a lack of consensus on the cardiometabolic consequences of mild subclinical hypothyroidism (SCH) among children. The objective of the current study was to compare lipid profiles in children with mild SCH with those of euthyroid children.

Study Design

Retrospective medical record review.

Patients

Children (ages 2‐18 years) who had undergone simultaneous measurement of TSH, free thyroxine (T4) and lipids. Lipids in children with mild SCH (TSH 5‐<10 mIU/L and normal free T4, n = 228) were compared with those in euthyroid children (n = 1215).

Results

TSH level was positively associated with total cholesterol and nonhigh density lipoprotein (non‐HDL) cholesterol [β 0.05(0.03‐0.08), P < .0001 and β 0.05(0.03‐0.08), P < .0001, respectively]. Total cholesterol was significantly higher in children and adolescents with mild SCH compared with euthyroid children (4.43 ± 1.14 mmol/L vs 4.2 ± 0.85 mmol/L, P = .0005). Similarly, non‐HDL cholesterol level was also higher in children with mild SCH relative to euthyroid children (3.08 ± 1.14 mmol/L vs 2.91 ± 0.8 mmol/L, P = .001). The adjusted odds ratio of having elevated total cholesterol and elevated non‐HDL cholesterol was greater in children with mild SCH compared with euthyroid children (OR 1.88, 95% CI; 1.28‐2.73; P = .001 and 1.72, 95% CI 1.2‐2.5; P = .003, respectively). The presence of thyroid autoimmunity was not associated with higher rates of dyslipidaemia.

Conclusions

Mild SCH in children and adolescents was associated with higher rates of elevated total cholesterol and elevated non‐HDL cholesterol. Randomized placebo controlled studies are warranted to determine if treatment of mild SCH in children leads to improvement in lipid profile.
Pharmacological and surgical treatment of nonreproductive outcomes in polycystic ovary syndrome: An overview of systematic reviews
Authors: Tay Chau T. , Joham Anju E. , Hiam Danielle S. , Gadalla Moustafa A. , Pundir Jyotsna , Thangaratinam Shakila , Teede Helena J. , Moran Lisa J.
Published: May 2018

Background

Polycystic ovary syndrome (PCOS) affects up to 13% women and is associated with significant complications. The quality of evidence supporting the recommendations on treatment of nonreproductive outcomes in PCOS is unknown.

Objective

To summarize and appraise the methodological quality of systematic reviews and meta‐analyses evaluating pharmacological and surgical treatments for nonreproductive outcomes in PCOS.

Methods

A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed from inception until 15th of September 2017. Article selection, data extraction and quality appraisal of included reviews were performed in duplicate. A narrative synthesis of the findings was conducted.

Results

This overview included 31 reviews. The quality was low for 7 (23%), moderate for sixteen (52%) and high for 8 reviews (26%). Two reviews assessed psychological outcomes. Metformin improved anthropometric (7 of 10 reviews), metabolic (4 of 14 reviews) and endocrine outcomes (3 of twelve reviews). Thiazolidinediones improved metabolic (2 of 5 reviews) and endocrine outcomes (one of 5 reviews) but worsened weight gain (5 of 5 reviews). Combined oral contraceptive pill (COCP) improved clinical hyperandrogenism (2 of 2 reviews). Statins improved lipid profile (3 of 3 reviews) and testosterone level (2 of 3 reviews). There was no conclusive evidence from included systematic reviews regarding the use of other interventions.

Conclusions

There is reliable evidence regarding the use of metformin for anthropometric outcomes and COCPs for hyperandrogenism in women with PCOS but not for other interventions. There is significant gap in knowledge regarding the management of psychological outcomes in women with PCOS which needs further evaluation.
International Classification of Functioning, Disability and Health Core Sets for cerebral palsy, autism spectrum disorder, and attention‐deficit–hyperactivity disorder
Authors: Schiariti Verónica , Mahdi Soheil , Bölte Sven
Published: May 2018

Aim

Capturing functional information is crucial in childhood disability. The International Classification of Functioning, Disability and Health (ICF) Core Sets promote assessments of functional abilities and disabilities in clinical practice regarding circumscribed diagnoses. However, the specificity of ICF Core Sets for childhood‐onset disabilities has been doubted. This study aimed to identify content commonalities and differences among the ICF Core Sets for cerebral palsy (CP), and the newly developed Core Sets for autism spectrum disorder (ASD) and attention‐deficit–hyperactivity disorder (ADHD).

Method

The categories within each Core Set were aggregated at the ICF component and chapter levels. Content comparison was conducted using descriptive analyses.

Results

The activities and participation component of the ICF was the most covered across all Core Sets. Main differences included representation of ICF components and coverage of ICF chapters within each component. CP included all ICF components, while ADHD and ASD predominantly focused on activities and participation. Environmental factors were highly represented in the ADHD Core Sets (40.5%) compared to the ASD (28%) and CP (27%) Core Sets.

Interpretation

International Classification of Functioning, Disability and Health Core Sets for CP, ASD, and ADHD capture both common but also unique functional information, showing the importance of creating condition‐specific, ICF‐based tools to build functional profiles of individuals with childhood‐onset disabilities.

What this paper adds

The International Classification of Functioning, Disability and Health (ICF) Core Sets for cerebral palsy (CP), autism spectrum disorder (ASD), and attention‐deficit–hyperactivity disorder (ADHD) include unique functional information.

The ICF‐based tools for CP, ASD, and ADHD differ in terms of representation and coverage of ICF components and ICF chapters.

Representation of environmental factors uniquely influences functioning and disability across ICF Core Sets for CP, ASD and ADHD.
First record of habitat of Daulocoris formosanus (Hemiptera: Aradidae): Colonies discovered in nests of Salganea taiwanensis ryukyuanus (Dictyoptera: Blaberidae)
Authors: Osaki Haruka , Shimamoto Shusuke , Kasuya Eiiti
Published: May 2018

We collected colonies of Daulocoris formosanus from nests of the subsocial wood‐feeding cockroach Salganea taiwanensis ryukyuanus for the first time. To understand the ecology of D. formosanus, we observed and characterized their behavior in a laboratory setting. We provide the first detailed record of the habitat, colony structure and feeding behavior of D. formosanus.
The ghost of introduction past: Spatial and temporal variability in the genetic diversity of invasive smallmouth bass
Authors: Diedericks Genevieve , Henriques Romina , von der Heyden Sophie , Weyl Olaf L. F. , Hui Cang
Published: May 2018

Understanding the demographic history of introduced populations is essential for unravelling their invasive potential and adaptability to a novel environment. To this end, levels of genetic diversity within the native and invasive range of a species are often compared. Most studies, however, focus solely on contemporary samples, relying heavily on the premise that the historic population structure within the native range has been maintained over time. Here, we assess this assumption by conducting a three‐way comparison of the genetic diversity of native (historic and contemporary) and invasive (contemporary) smallmouth bass (Micropterus dolomieu) populations. Analyses of a total of 572 M. dolomieu samples, representing the contemporary invasive South African range, contemporary and historical native USA range (dating back to the 1930s when these fish were first introduced into South Africa), revealed that the historical native range had higher genetic diversity levels when compared to both contemporary native and invasive ranges. These results suggest that both contemporary populations experienced a recent genetic bottleneck. Furthermore, the invasive range displayed significant population structure, whereas both historical and contemporary native US populations revealed higher levels of admixture. Comparison of contemporary and historical samples showed both a historic introduction of M. dolomieu and a more recent introduction, thereby demonstrating that undocumented introductions of this species have occurred. Although multiple introductions might have contributed to the high levels of genetic diversity in the invaded range, we discuss alternative factors that may have been responsible for the elevated levels of genetic diversity and highlight the importance of incorporating historic specimens into demographic analyses.
Scaling the nexus: Towards integrated frameworks for analysing water, energy and food
Authors: McGrane Scott J. , Acuto Michele , Artioli Francesca , Chen Po‐Yu , Comber Robert , Cottee Julian , Farr‐Wharton Geremy , Green Nicola , Helfgott Ariella , Larcom Shaun , McCann Julie A. , O'Reilly Patrick , Salmoral Gloria , Scott Marian , Todman Lindsay C. , van Gevelt Terry , Yan Xiaoyu
Published: May 2018

The emergence of the water–energy–food (WEF) nexus has resulted in changes to the way we perceive our natural resources. Stressors such as climate change and population growth have highlighted the fragility of our WEF systems, necessitating integrated solutions across multiple scales. While a number of frameworks and analytical tools have been developed since 2011, a comprehensive WEF nexus tool remains elusive, hindered in part by our limited data and understanding of the interdependencies and connections across the WEF systems. To achieve this, the community of academics, practitioners and policy‐makers invested in WEF nexus research are addressing several critical areas that currently remain as barriers. First, the plurality of scales (e.g., spatial, temporal, institutional, jurisdictional) necessitates a more comprehensive effort to assess interdependencies between water, energy and food, from household to institutional and national levels. Second, and closely related to scale, a lack of available data often hinders our ability to quantify physical stocks and flows of resources. Overcoming these barriers necessitates engaging multiple stakeholders, and using experiences and local insights to better understand nexus dynamics in particular locations or scenarios, and we exemplify this with the inclusion of a UK‐based case study on exploring the nexus in a particular geographical area. We elucidate many challenges that have arisen across nexus research, including the impact of multiple scales in operation, and concomitantly, what impact these scales have on data accessibility. We assess some of the critical frameworks and tools that are applied by nexus researchers and articulate some of the steps required to develop from nexus thinking to an operationalisable concept, with a consistent focus on scale and data availability.
Critical role of the Ror‐family of receptor tyrosine kinases in invasion and proliferation of malignant pleural mesothelioma cells
Authors: Saji Takeshi , Nishita Michiru , Ogawa Hiroyuki , Doi Takefumi , Sakai Yasuhiro , Maniwa Yoshimasa , Minami Yasuhiro
Published: May 2018

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor prognosis and closely related to exposure to asbestos. MPM is a heterogeneous tumor with three main histological subtypes, epithelioid, sarcomatoid, and biphasic types, among which sarcomatoid type shows the poorest prognosis. The Ror‐family of receptor tyrosine kinases, Ror1 and Ror2, is expressed in various types of tumor cells at higher levels and affects their aggressiveness. However, it is currently unknown whether they are expressed in and involved in aggressiveness of MPM. Here, we show that Ror1 and Ror2 are expressed in clinical specimens and cell lines of MPM with different histological features. Studies using MPM cell lines indicate that expression of Ror2 is associated tightly with high invasiveness of MPM cells, whereas Ror1 can contribute to their invasion in the absence of Ror2. However, both Ror1 and Ror2 promote proliferation of MPM cells. We also show that promoted invasion and proliferation of MPM cells by Ror signaling can be mediated by the Rho‐family of small GTPases, Rac1, and Cdc42. These findings elucidate the critical role of Ror signaling in promoting invasion and proliferation of MPM cells.
Job search inefficiency and optimal policies in the presence of an informal sector
Authors: Flórez Luz A.
Published: May 2018

In this paper I use a search and matching model to analyze efficiency in an economy with an informal sector, defined as unregulated self‐employment that cannot be observed by the government. Initially I show that the market solution for this kind of economy is inefficient. Subsequently I introduce various government policies that could correct this inefficiency. These policies include social security payments, severance payments, formal taxes, and job creation subsidies. According to this analysis the most effective policy, which restores efficiency while at the same time reducing informality levels in the labor market, is a tax credit. In this model a tax credit provides incentives for informal workers to participate in the formal sector by reducing the tax burden they have to pay as formal employees. As a consequence these workers have a higher probability of finding a higher‐productivity job in the formal sector, which in turn increases the overall efficiency of the economy. This finding is interesting in so far as it provides a theoretical rationale for anti‐informality policies that reduce informality through more rather than less social protection. The paper is therefore a modest contribution toward a policy paradigm in which reducing levels of informality and poverty and providing social protection for workers are seen as complementary rather than contradictory goals.
Promoting exercise behaviour in a secure mental health setting: Healthcare assistant perspectives
Authors: Kinnafick Florence‐Emilie , Papathomas Anthony , Regoczi Dora
Published: May 2018

Individuals with severe mental illness engage in significantly less amounts of physical activity than the general population. A secure mental health setting can exacerbate barriers to exercise, and facilitate physical inactivity and sedentary behaviour. Healthcare assistants are intimately involved in the daily lives of patients and, therefore, should be considered integral to exercise promotion in secure mental health settings. Our aim was to explore healthcare assistants’ perceptions of exercise and their attitudes to exercise promotion for adult patients in a secure mental health hospital. Qualitative semi‐structured interviews were conducted with 11 healthcare assistants from a large UK‐based secure mental health hospital. Topics included healthcare assistants’ personal experiences of exercise within a secure facility, their perceptions of exercise as an effective treatment tool for mental health, and their perceived roles and responsibilities for exercise promotion. Thematic analysis was used to analyse the data. Three main themes were identified: (i) exercise is multi‐beneficial to patients, (ii) perceived barriers to effective exercise promotion, and (iii) strategies for effectives exercise promotion. Healthcare assistants considered exercise to hold patient benefits. However, core organizational and individual barriers limited healthcare assistants’ exercise promotion efforts. An informal approach to exercise promotion was deemed most effective to some, whereas others committed to more formal strategies including compulsory sessions. With education and organizational support, we propose healthcare assistants are well placed to identify individual needs for exercise promotion. Their consultation could lead to more efficacious, person‐sensitive interventions.
Bioenergetic modulators hamper cancer cell viability and enhance response to chemotherapy
Authors: Tavares‐Valente Diana , Granja Sara , Baltazar Fátima , Queirós Odília
Published: May 2018

Gliomas are characterized by a marked glycolytic metabolism with a consequent production of massive amounts of lactate, even in the presence of normal levels of oxygen, associated to increased invasion capacity and to higher resistance to conventional treatment. This work aimed to understand how the metabolic modulation can influence tumour aggressive features and its potential to be used as complementary therapy. We assessed the effect of bioenergetic modulators (BMs) targeting different metabolic pathways in glioma cell characteristics. The in vivo effect of BMs was evaluated using the chicken chorioallantoic membrane model. Additionally, the effect of pre‐treatment with BMs in the response to the antitumour drug temozolomide (TMZ) was analysed in vitro. Cell treatment with the BMs induced a decrease in cell viability and in migratory/invasion abilities, as well as modifications in metabolic parameters (glucose, lactate and ATP) and increased the cytotoxicity of the conventional drug TMZ. Furthermore, all BMs decreased the tumour growth and the number of blood vessels in an in vivo model. Our results demonstrate that metabolic modulation has the potential to be used as therapy to decrease the aggressiveness of the tumours or to be combined with conventional drugs used in glioma treatment.
Reflectance confocal microscopy: a crucial role for actinic keratosis treatment monitoring
Authors: Pellacani G. , Longo C.
Published: May 2018

Linked article: This is a commentary on P. Ishioka et al., pp. 1155–1163 in this issue. To view this article visit https://doi.org/10.1111/jdv.14716
Secukinumab significantly reduces psoriasis‐related work impairment and indirect costs compared with ustekinumab and etanercept in the United Kingdom
Authors: Warren R.B. , Halliday A. , Graham C.N. , Gilloteau I. , Miles L. , McBride D.
Published: May 2018

Background

Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown.

Objective

To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK).

Methods

This was a post hoc analysis of work impairment data collected in theCLEARstudy (secukinumab vs. ustekinumab) and applied to theFIXTUREstudy (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (i) overall work impairment derived from Work Productivity and Activity Impairment data collected inCLEARat 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (ii) weekly/annual work productivity loss byPASIresponse level; (iii) weekly and annual indirect costs byPASIresponse level, based on hours of work productivity loss; and (iv) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients inCLEARat Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different time points and with patient cohorts, includingFIXTURE.

Results

InCLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higherPASI:PASI < 50: 22.8%/7.60 h;PASI50–74: 13.3%/4.45 h;PASI75–89: 6.4%/2.14 h;PASI ≥ 90: 4.9%/1.65 h. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12;P = 0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17;Ρ<0.0001). Average annual indirect cost savings with secukinumab were £355 vs. ustekinumab and £1061 versus etanercept. Results at 52 weeks were similar.

Conclusions

Secukinumab significantly reduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the United Kingdom.
Hyperspectral imaging system in the delineation of Ill‐defined basal cell carcinomas: a pilot study
Authors: Salmivuori M. , Neittaanmäki N. , Pölönen I. , Jeskanen L. , Snellman E. , Grönroos M.
Published: May 2018

Background

Basal cell carcinoma (BCC) is the most common skin cancer in the Caucasian population. Eighty per cent of BCCs are located on the head and neck area. Clinically ill‐defined BCCs often represent histologically aggressive subtypes, and they can have subtle subclinical extensions leading to recurrence and the need for re‐excisions.

Objectives

The aim of this pilot study was to test the feasibility of a hyperspectral imaging system (HIS) in vivo in delineating the preoperatively lateral margins of ill‐defined BCCs on the head and neck area.

Methods

Ill‐defined BCCs were assessed clinically with a dermatoscope, photographed and imaged with HIS. This was followed by surgical procedures where the BCCs were excised at the clinical border and the marginal strip separately. HIS, with a 12‐cm2 field of view and fast data processing, records a hyperspectral graph for every pixel in the imaged area, thus creating a data cube. With automated computational modelling, the spectral data are converted into localization maps showing the tumour borders. Interpretation of these maps was compared to the histologically verified tumour borders.

Results

Sixteen BCCs were included. Of these cases, 10 of 16 were the aggressive subtype of BCC and 6 of 16 were nodular, superficial or a mixed type. HIS delineated the lesions more accurately in 12 of 16 of the BCCs compared to the clinical evaluation (4 of 16 wider and 8 of 16 smaller by HIS). In 2 of 16 cases, the HIS‐delineated lesion was wider without histopathological confirmation. In 2 of 16 cases, HIS did not detect the histopathologically confirmed subclinical extension.

Conclusions

HIS has the potential to be an easy and fast aid in the preoperative delineation of ill‐defined BCCs, but further adjustment and larger studies are warranted for an optimal outcome.
Successful despite poor flight performance: range expansion is associated with enhanced exploratory behaviour and fast development
Authors: Reim Elisabeth , Blesinger Simone , Förster Lisa , Fischer Klaus
Published: May 2018

Anthropogenic interference forces species to respond to changing environmental conditions. One possible response is dispersal and concomitant range shifts, allowing individuals to escape unfavourable conditions or to track the shifting climate niche. Range expansions depend on both dispersal capacity and the ability to establish populations beyond the former range. We here compare well‐established core populations with recently established edge populations in the currently northward expanding butterflyLycaena tityrus. Edge populations were characterized by shorter development times and smaller size, a higher sensitivity to high temperature and an enhanced exploratory behaviour. The differences between core and edge populations found suggest adaptation to local climates and an enhanced dispersal ability in edge populations. In particular, enhanced exploratory behaviour may be advantageous in all steps of the dispersal process and may have facilitated the current range expansion. This study describes differences associated with a current range expansion, knowledge which might be useful for a better understanding of species responses to environmental change. We further report on variation between males and females in morphology and flight behaviour, with males showing a longer flight endurance and more pronounced exploratory behaviour than females.
The Risk‐Taking Channel of Monetary Policy: Exploring All Avenues
Authors: BONFIM DIANA , SOARES CARLA
Published: May 2018

The literature on the risk‐taking channel of monetary policy grew quickly, leading to scattered evidence. We examine this channel through different angles, exploring detailed information on loan origination and performance. Ex ante riskier borrowers receive more funding at the extensive margin when interest rates are lower. Ex post performance is independent of the level of interest rates at origination. Still, loans granted in periods of very low and stable interest rates show higher default rates once interest rates start to increase. Risk‐taking is stronger among banks with lower capital ratios, suggesting that this channel may be linked to managerial incentives for risk‐shifting.
A Phillips Curve with Anchored Expectations and Short‐Term Unemployment
Authors: BALL LAURENCE , MAZUMDER SANDEEP
Published: May 2018

This paper examines the behavior of U.S. core inflation, as measured by the weighted median of industry price changes. We find that core inflation since 1985 is well‐explained by an expectations‐augmented Phillips curve in which expected inflation is measured with professional forecasts and labor‐market slack is captured by the short‐term unemployment rate. We also find that expected inflation was backward‐looking until the late 1990s, but then became strongly anchored at the Federal Reserve's target. This shift in expectations changed the relationship between inflation and unemployment from an accelerationist Phillips curve to a level‐level Phillips curve. Our specification explains why high unemployment during the Great Recession did not reduce inflation greatly: partly because inflation expectations were anchored, and partly because short‐term unemployment rose less sharply than total unemployment.
Obstetric outcomes in pregnancy with pulmonary hypertension: A retrospective study of 78 cases at one center
Authors: Zhu Cai‐xia , Xiong Wei , Chen Han‐qing , Niu Gang , Wang Zi‐lian
Published: May 2018

Objective

To identify the vary of obstetric outcomes by the severity of pulmonary hypertension (PH).

Methods

A retrospective study involved pregnancies with PH in one certain academic institution. Total 78 pregnancies with PH were classified into three groups according the mean pulmonary arterial systolic pressure: mean pulmonary arterial systolic pressure 30–49 mm Hg (mild‐PH group), mean pulmonary arterial systolic pressure 50–69 mm Hg (moderate‐PH group) and mean pulmonary arterial systolic pressure ≥ 70 mm Hg (severe‐PH group). The clinical features and obstetric outcomes were described and compared among three groups.

Results

The incidence of PH was 0.23%, including 57 cases in mild‐PH group, 10 cases in moderate‐PH group and 11 cases in severe‐PH group. Meanwhile, pregnancies with mild PH present NYHA class I/II (P < 0.001). General anesthesia (P < 0.001) and advanced intensive care (P = 0.011) were supplied for pregnancies with severe PH. There was no significant difference in rate of caesarean delivery. Furthermore, severity of PH increased the risk of neonatal death (P = 0.040).

Conclusion

The severity of PH seems to be a poor prognosis of neonatal death. Intensive care should be provided for pregnancies with severe PH.
Long‐term dienogest administration in patients with symptomatic adenomyosis
Authors: Neriishi Kazuaki , Hirata Tetsuya , Fukuda Shinya , Izumi Gentaro , Nakazawa Akari , Yamamoto Naoko , Harada Miyuki , Hirota Yaushi , Koga Kaori , Wada‐Hiraike Osamu , Fujii Tomoyuki , Osuga Yutaka
Published: May 2018

Aim

Adenomyosis is a common gynecological disorder that causes dysmenorrhea, hypermenorrhea and metrorrhagia. Previously, we reported that 24 weeks of dienogest treatment is highly effective for pain in symptomatic adenomyosis. Up to present, there is no report that describes treatment of adenomyosis with long‐term dienogest administration for more than 2 years. In this retrospective cohort study, we investigated the course of long‐term dienogest treatment in patients with symptomatic adenomyosis.

Methods

This is a retrospective cohort study. Dienogest was continuously administered at a dose of 2 mg daily for patients with symptomatic adenomyosis. The outcome of long‐term administration of dienogest was investigated, and the characteristics of patients were compared between discontinued cases and long‐term administration cases.

Results

Two patients were excluded from this study because of transfer to another hospital or discontinuation due to infertility treatment. Twelve of 18 patients (66.7%) received dienogest until menopause or for a period of >80 months. Four cases (22.2%) discontinued dienogest treatment because of severe metrorrhagia. In the discontinued cases because of severe metrorrhagia, the pain score for dysmenorrhea and serum CA125 level at baseline significantly elevated, and the hemoglobin level at baseline and the frequency of type 2 adenomyosis significantly decreased, compared to those with long‐term use. Moreover, long‐term dienogest use did not decrease the serum estradiol level.

Conclusion

Our report suggests that dienogest is tolerable for long‐term use until menopause and can be an alternative treatment option in some patients, especially those with type 2 adenomyosis, to avoid hysterectomy.
Recurrence of diet‐treated gestational diabetes in primiparous women in northern Zhejiang, China: Epidemiology, risk factors and implications
Authors: Wang Na , Lu Weina , Xu Yongliang , Mao Shuhui , He Man , Lin Xihua , Zhou Jiaqiang
Published: May 2018

Aim

This study sought to determine the rate of recurrence of gestational diabetes mellitus (GDM) recurrence during the second pregnancies of women who were diagnosed with GDM during their first pregnancies, to identify risk factors associated with the probability of such recurrence and to evaluate the influence of GDM recurrence on pregnancy outcomes in north Zhejiang, China, after the recent adjustment to the nation's childbirth policy.

Methods

A retrospective longitudinal study was performed in north Zhejiang, China (at Jiaxing Maternal and Child Health Hospital). A total of 128 women who delivered two sequential live singleton infants and were diagnosed with diet‐treated GDM during their first pregnancies were included.

Results

According to the 2013 World Health Organization diagnostic criteria for diabetes during pregnancy, the prevalence of gestational diabetes was 11.02% in northern Zhejiang. The recurrence rate of GDM in northern Zhejiang was 43.75% (56/128). The age at second pregnancy, weight gain during pregnancy, interpregnancy interval and macrosomia during the index pregnancy were risk factors for GDM recurrence. Among those women with recurrent GDM, GDM developed earlier and caesarean section was more frequently required during the second pregnancy; in addition, the second pregnancy was associated with more premature and low birthweight infants but less macrosomia.

Conclusion

The recurrence rate of GDM is high in northern Zhejiang. Glucose monitoring and management are needed during subsequent pregnancies for patients who previously presented with GDM to improve maternal and fetal outcomes.
Assessing patient satisfaction with the Medication Management Review service delivered in Jordan
Authors: Basheti Iman A. , Tadros Odate K.I. , Alnajjar Munther S. , Aburuz Salah
Published: May 2018

Objective

To investigate the effect of the Medication Management Review (MMR) service on the number of treatment-related problems (TRPs), patient satisfaction and factors affecting patient satisfaction.

Methods

This prospective, randomized controlled trial was conducted at community pharmacies in Amman, Jordan. Eligible patients were randomized into active and control groups. A validated Pharmaceutical Care Manual was used for data collection and to identify TRPs for both groups. Identified TRPs for patients in the active group were resolved at the pharmacist level or sent to the patients’ physicians for approval and implementation. Patients in both groups were followed up at 3 months to determine the number of TRPs end of the study. Patients in the active group completed a validated, Likert scale MMR-satisfaction questionnaire. Factors affecting satisfaction were assessed through multiple regression analysis.

Key findings

Outpatients with chronic conditions (n = 160) were recruited into the study, with mean age 53.01 ± 15.39; mean number of medical conditions of 3.56 ± 1.15 and 4.73 ± 1.79 mean number of medications. A mean number of 5.37 ± 3.01 TRPs per patient was identified, with no significant difference between both groups (active group n = 82, 5.57 ± 2.68; control n = 78, 5.18 ± 3.36, P = 0.412). At follow-up, significantly lower number of TRPs were identified for patients in the active group compared to patients in the control group (1.06 ± 1.30 versus 4.53 ± 3.43, P < 0.001). Majority of patients were satisfied/very satisfied with the service (n = 77, 94.5%). A lower number of TRPs at follow-up (B = −0.438; t = −4.477, P < 0.001) and higher number of TRPs agreed upon and implemented (B = 0.553; t = 6.949, P < 0.001) were significantly associated with higher level of patient satisfaction.

Conclusion

The MMR has proven to be an effective pharmaceutical care service when delivered in a developing country, such as Jordan. It led to high patient satisfaction, which was significantly associated with lower number of TRPs at follow-up.
Osseointegration in osteoporotic‐like condition: A systematic review of preclinical studies
Authors: Dereka X. , Calciolari E. , Donos N. , Mardas N.
Published: May 2018

Osteoporosis is one of the most common skeletal disorders affecting a significant percentage of people worldwide. Research data suggested that systemic diseases such as osteoporosis could act as risk factors for osseointegration, jeopardizing the healing process and thus the predictability of dental implant success on compromised patients. It is well accepted that preclinical studies in animal models reproducing the osteoporotic condition are one of the most important stages in the research of new biomaterials and therapeutic modalities. The aim of this systematic review was to investigate whether osteoporosis compromises dental implant osseointegration in experimental osteoporotic‐like conditions. A 3‐stage systematic literature research was conducted in MEDLINE via OVID and EMBASE up to and including March 2017. Experimental studies reporting on dental implant osseointegration on different osteoporotic animal models were assessed. The studies had to report on the percentage of bone‐to‐implant contact (%BIC) as the primary outcome. ARRIVE guidelines for reporting on animal research were applied to evaluate the methodological quality and risk of bias of the studies. Fifty‐seven studies met the inclusion criteria and were assessed qualitatively. The most adopted animal model was the rat. A variability of %BIC values was observed, ranging from 30% to 99% and from 26% to 94% for the healthy and osteoporotic group, respectively. The great majority (47) of the included studies concluded that estrogen deficiency significantly affects BIC values, 9 studies stated that it was not possible to observe statistical differences in BIC between ovariectomized and healthy groups and 1 study did not provide a comparison between the healthy and osteoporotic group. Owing to the great heterogeneity in implant surface, study design, observation time‐points, site of implant placement and reported outcomes, a meta‐analysis could not be performed. An overall high risk of bias was observed, owing to the limited information on animal housing and husbandry, baseline characteristics and health status, ethical statement and allocation to the experimental groups provided. Although the available studies seem to suggest a lower osseointegration in osteoporotic‐like conditions, no robust conclusions can be drawn due to the great heterogeneity and overall low quality of the available studies. Future studies with emphasis on minimizing the possible sources of bias and evaluating osseointegration of dental implants placed into jawbones instead of long bones are warranted.
Optimizing medication management for patients with cirrhosis: Evidence‐based strategies and their outcomes
Authors: Thomson Mary J. , Lok Anna S. , Tapper Elliot B.
Published: May 2018

Cirrhosis is a morbid condition associated with frequent hospitalizations and high mortality. Management of cirrhosis requires complex medication regimens to treat underlying liver disease, complications of cirrhosis and comorbid conditions. This review examines the complexities of medication management in cirrhosis, barriers to optimal medication use, and potential interventions to streamline medication regimens and avoid medication errors. A literature review was performed by searching PUBMED through December 2017 and article reference lists to identify articles relevant to medication management, complications, adherence, and interventions to improve medication use in cirrhosis. The structural barriers in cirrhosis include sheer medication complexity related to the number of medications and potential for cognitive impairment in this population, faulty medication reconciliation and limited adherence. Tested interventions have included patient self‐education, provider driven patient education, intensive case management including medication blister packs and smartphone applications. Initiatives are needed to improve patient, caregiver and provider education on appropriate use of medications in patients with cirrhosis. A multidisciplinary team should be established to coordinate care with close monitoring, address patient and caregiver concerns, and to provide timely access to outpatient evaluation of urgent/complex issues. Future studies evaluating the clinical outcomes and cost effectiveness of interventions are needed.
Relationship between nocturnal polyuria and non‐dipping blood pressure in male patients with lower urinary tract symptoms
Authors: Takayama Misato , Omori So , Iwasaki Kazuhiro , Shiomi Ei , Takata Ryo , Sugimura Jun , Abe Takaya , Obara Wataru
Published: May 2018

Objective

The aim of the present study was to examine factors of nocturnal polyuria and blood pressure variability in male patients with lower urinary tract symptoms (LUTS) who were treated.

Methods

Two hundred and forty‐two male patients with LUTS who were treated recorded frequency volume charts. We investigated their urinary condition and characteristics, medical history, and medications. Thirty‐four of these patients underwent ambulatory blood pressure monitoring (ABPM) for 24 hours to evaluate blood pressure variability.

Results

In the present study, 194 patients (80.2%) had nocturia and 136 (56.2%) had nocturnal polyuria (NP). Among patients with nocturia (≥2 voids/night), 130 (67.0%) had nocturnal polyuria, and 26 of those with nocturia (13.4%) had reduced functional bladder capacity. The use of 2 or more antihypertensive medications was significantly higher in the NP than non‐NP group (22.8% vs. 12.3%; P = .035). Significantly more patients in the NP group had non‐dipping blood pressure (P = .037). Non‐dipping blood pressure was considered a potential factor for NP.

Conclusion

We suggest that treatment of non‐dipping blood pressure may improve NP.