bluuebunny/crossref_metadata_2025 huggingface dataset:
Crizotinib versus platinum‐based double‐agent chemotherapy as the first line treatment in advanced anaplastic lymphoma kinase‐positive lung adenocarcinoma
Authors: Zhang Quan , Qin Na , Wang Jinghui , Lv Jialin , Yang Xinjie , Li Xi , Nong Jingying , Zhang Hui , Zhang Xinyong , Wu Yuhua , Zhang Shucai
Published: April 2015

Background

To explore the efficacy and safety of crizotinib versus platinum‐based double agent chemotherapy as the first‐line treatment in patients with advanced anaplastic lymphoma kinase (ALK)‐positive lung adenocarcinoma.

Method

We retrospectively analyzed data from 19 patients with advanced ALK‐positive lung adenocarcinoma who had received no previous systemic treatment for advanced disease. Seven patients received oral crizotinib at a dose of 250 mg twice daily; 12 patients were administered standard chemotherapy (pemetrexed, paclitaxel, vinorelbine or gemcitabine plus either cisplatin or carboplatin) every three weeks for up to six cycles. The primary endpoint was overall response rate (ORR), disease control rate (DCR), and safety.

Results

The ORR was significantly higher with crizotinib than with chemotherapy (83.3% in the crizotinib vs. 25.0% in the chemotherapy group, P < 0.05); the DCRs were 100% and 75%, respectively (P < 0.05). The common adverse events associated with crizotinib were visual abnormality and diarrhea, whereas those associated with chemotherapy were neutropenia and nausea. In the crizotinib group, liver aminotransferase elevation (adverse events grade 3 or 4) occurred in one patient (14.3%). In the chemotherapy group, the same grade neutropenia adverse event occurred in two patients (16.6%). The incidence of treatment‐related grade 3 or 4 adverse events was similar in both groups. Compared with chemotherapy, crizotinib was associated with a greater reduction in lung cancer symptoms and a greater improvement in quality of life.

Conclusion

As a first‐line treatment, crizotinib was superior to platinum‐based double chemotherapy in patients with previously untreated advanced ALK‐positive lung adenocarcinoma. Therefore, crizotinib is an optimal therapy as a first‐line treatment in these patients.
Cyclic Vomiting Presentations Following Marijuana Liberalization in Colorado
Authors: Kim Howard S. , Anderson John D. , Saghafi Omeed , Heard Kennon J. , Monte Andrew A.
Published: April 2015

Objectives

Case reports have described a syndrome of cyclic vomiting associated with chronic marijuana use, termed cannabinoid hyperemesis syndrome. The primary objective was to determine the prevalence of patients presenting with cyclic vomiting before and after the liberalization of medical marijuana in Colorado in 2009. The secondary objective was to describe the odds of marijuana use among cyclic vomiting visits in these same time periods.

Methods

This was a cross‐sectional study of cyclic vomiting visits to the emergency department (ED) before and after marijuana liberalization. ED visits with International Classification of Diseases, ninth revision, coding for cyclic vomiting or that met diagnostic criteria for cyclic vomiting by the Rome III criteria were included.

Results

The authors reviewed 2,574 visits and identified 36 patients diagnosed with cyclic vomiting over 128 visits. The prevalence of cyclic vomiting visits increased from 41 per 113,262 ED visits to 87 per 125,095 ED visits after marijuana liberalization, corresponding to a prevalence ratio of 1.92 (95% confidence interval [CI] = 1.33 to 2.79). Patients with cyclic vomiting in the postliberalization period were more likely to have marijuana use documented than patients in the preliberalization period (odds ratio = 3.59, 95% CI = 1.44 to 9.00).

Conclusions

The prevalence of cyclic vomiting presentations nearly doubled after the liberalization of medical marijuana. Patients presenting with cyclic vomiting in the postliberalization period were more likely to endorse marijuana use, although it is unclear whether this was secondary to increased marijuana use, more accurate marijuana reporting, or both.
Galanin is Co‐Expressed with Substance P, Calbindin and Corticotropin‐Releasing Factor (CRF) in The Enteric Nervous System of the Wild Boar (Sus scrofa) Small Intestine
Authors: Czujkowska A. , Arciszewski M. B.
Published: April 2015

Galanin is a neuropeptide widely present in the enteric nervous system of numerous animal species and exhibiting neurotransmittery/neuromodulatory roles. Colocalization patterns of galanin with substance P (SP), corticotropin‐releasing factor (CRF) and calbindin were studied in the small intestine of the wild boar using immunofluorescence technique. We demonstrated the presence of SP in substantial populations of galanin‐immunoreactive (IR) submucous neurons. Additionally, different amounts of nerve fibres exhibiting simultaneous presence of galanin and SP were noted in the small intestinal smooth musculature, submucous ganglia, lamina muscularis mucosae and mucosa. In the wild boar duodenum, jejunum and ileum, the co‐expression of galanin and calbindin was limited to minor populations of submucous neurons only. Single galanin‐/CRF‐IR nerve fibres were exclusively present in the duodenal and jejunal (but not ileal) mucosa. These results strongly suggest that galanin participates in neuronal control of the wild boar small intestine also by functional co‐operation with other biologically active neuropeptides.
Enforced abstinence from tobacco during in‐patient dual‐diagnosis treatment improves substance abuse treatment outcomes in smokers
Authors: Stuyt Elizabeth B.
Published: April 2015

Background and Objectives

Although the prevalence of tobacco use in those in substance abuse treatment is known to be quite high, most treatment programs do not address tobacco. The purpose of this study was to determine substance abuse recovery rates a year after treatment in a fully integrated, 90‐day inpatient, dual diagnosis treatment program where patients are required to quit tobacco use in addition to drug and alcohol use for the duration of their 3 month stay. Tobacco is treated in the same way as other drugs and alcohol.

Methods

One hundred fifty‐four patients enrolled in a yearlong follow‐up after treatment study consisting of monthly phone contact to assess recovery from substance abuse.

Results

One hundred forty (n=140) patients completed the year follow‐up. At the time of entry into the program 120 (86%) were using tobacco daily. At the end of the year this decreased to 102 (73%). Patients who were using tobacco were more likely to relapse to other drugs or alcohol (p = .01). Patients who actively attempted to abstain from tobacco after treatment were significantly more likely to remain continuously abstinent throughout the year (p = .03).

Conclusions

This study demonstrates that tobacco use is correlated with relapse and addressing tobacco in treatment as seriously as and in the same fashion as other drugs, improves outcomes.

Scientific Significance

When provided with a tobacco free treatment environment for 90 days, patients with substance abuse and mental illness can and do make the decision to quit tobacco and stay quit, aiding their ability to remain sober. (Am J Addict 2015;24:252–257)
HPV‐DNA sperm infection and infertility: from a systematic literature review to a possible clinical management proposal
Authors: Foresta C. , Noventa M. , De Toni L. , Gizzo S. , Garolla A.
Published: April 2015

The objectives of this study were to investigate the implications of human papillomavirus (HPV) sperm infection on male fertility, impairment of sperm parameters, and possible alteration of sperm nuclear status and to identify a possible effective management of infertile men with HPV sperm infection. We employed a systematic review and clinical management proposal at the Centers for Reproductive and Health care for treating infertile male patients with HPV infection. Literature search was carried out in electronic databases in the last two decades. We focused our attention on: (i) HPV sperm prevalence (ii) HPV‐related alteration of sperm parameters; (iii) molecular mechanisms of HPV semen infection and infertility. The main outcome measures were HPV prevalence in infertile male patients and semen parameters. The prevalence of HPV sperm infection ranges between 2 and 31% in men from general population and between 10 and 35.7% in men affected by unexplained infertility. The presence of HPV in semen is associated with an impairment of sperm motility and the presence of anti‐sperm antibodies. The molecular mechanisms underlying impairment of sperm motility apparatus need further evaluations. A greater attention should be applied to assess HPV sperm infection, particularly in men undergoing assisted reproduction techniques cycle for male infertility or sperm banking. It would be useful to perform HPV test and fluorescent in situ hybridization analysis for HPV in semen from these patients both at first admission, to define the possible presence and localization of semen infection, and after 6 months, to assess the possible virus clearance retrieval on normal sperm parameters.
Impact of visceral obesity on outcomes of laparoscopic colorectal surgery: a meta‐analysis
Authors: Yang Tinghan , Wei Mingtian , He Yazhou , Deng Xiangbing , Wang Ziqiang
Published: April 2015

Background

Excessive visceral fat could influence surgical difficulty of laparoscopic colorectal surgery. With the use of visceral fat area measured by computed tomography, surgeons could quantify the amount of visceral fat. The aim of the present meta‐analysis is to quantitatively combine studies in order to determine the impact of visceral obesity on laparoscopic colorectal surgery.

Methods

A systematic search of literature (PubMed, EMBASE, the Cochrane Library) was performed to identify studies evaluating the impact of visceral obesity on laparoscopic colorectal surgery.

Results

Four studies were included in this meta‐analysis. Meta‐analysis revealed that visceral obesity was associated with longer operative time (weighted mean difference (WMD) 24.42, 95% confidence interval (CI) 12.98–35.86), less lymph nodes harvest (WMD −5.99, 95% CI −8.31 to −3.67), more conversion to open procedure (odds ratio (OR) 2.24, 95% CI 1.05–4.78), higher morbidity (OR 2.33, 95% CI 1.56–3.48), more surgical site infection (OR 3.22, 95% CI 1.95–5.32) and more anastomotic leakage (OR 2.40, 95% CI 1.06–5.44).

Conclusion

The present study shows that visceral obesity is associated with increased surgical difficulty and post‐operative morbidity of laparoscopic colorectal surgery but does not affect post‐operative recovery thanks to laparoscopic procedure.
Systematic review: dietary fibre andFODMAP‐restricted diet in the management of constipation and irritable bowel syndrome
Authors: Rao S. S. C. , Yu S. , Fedewa A.
Published: April 2015

Background

Dietary fibre supplements have been advocated for the management of chronic constipation (CC) and irritable bowel syndrome (IBS). Recently, a fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) restricted diet has been recommended forIBS.

Aim

To systematically examine recent evidence for dietary interventions with fibre inCCandIBSandFODMAP‐restricted diet inIBS, and provide recommendations.

Methods

We searchedPUBMED,MEDLINE,OVIDandCOCHRANEdatabases from 2004 to 2014. Published studies in adults withCCandIBSand constipation‐predominantIBS(IBS‐C) that compared fibre with placebo/alternative andFODMAP‐restricted diet with alternative were included.

Results

Of 550 potentially eligible clinical trials on fibre, 11 studies were found and of 23 potentially eligible studies onFODMAPs, six were found. A meta‐analysis was not performed due to heterogeneity and methodological quality. Fibre was beneficial in 5/7 studies inCCand 3/3 studies inIBS‐C.FODMAP‐restricted diet improved overallIBSsymptoms in 4/4 andIBS‐C symptoms in 1/3 studies and three studies did not meet inclusion criteria. There were significant disparities in subject selection, interventions and outcome assessments in both fibre andFODMAPs studies.

Conclusions

Fibre supplementation is beneficial in mild to moderateCCandIBS‐C, although larger, more rigorous and long‐termRCTs are needed (Fair evidence–LevelII, Grade B). Although theFODMAP‐restricted diet may be effective in short‐term management of selected patients withIBS(Fair evidence–LevelII, Grade C) andIBS‐C (Poor evidence–LevelIII, Grade C), more rigorous trials are needed to establish long‐term efficacy and safety, particularly on colonic health and microbiome.
Clinical characteristics and early treatment outcomes of follicular lymphoma in young adults
Authors: Gangatharan Shane A. , Maganti Manjula , Kuruvilla John G. , Kukreti Vishal , Tiedemann Rodger E. , Gospodarowicz Mary K. , Hodgson David C. , Sun Alex , Tsang Richard W. , Pintilie Melania , Crump Michael
Published: April 2015

Follicular lymphoma (FL) in young adults (YA, <40 years old) is uncommon, and the clinical characteristics and outcomes of this group are not well defined. We conducted a retrospective database review of 427 patients with newly diagnosed FL aged 65 years or less registered at Princess Margaret Cancer Centre between 1995 and 2010. YA (n = 61) and those 40–65 (n = 366) were compared with regards to clinical stage at diagnosis, FL International Prognostic Index (FLIPI) score, and the following clinical outcomes: time to second treatment, cause‐specific survival (CSS) and overall survival (OS). At diagnosis, stage and FLIPI score were similar, as were the proportion of patients requiring therapy (YA 75% versus older adults 71%). Median follow‐up was 8·1 years. Time to second therapy was similar in both age groups (5‐year probability 23% YA versus 27% older adults; Gray's P‐value = 0·76). Ten‐year OS was significantly higher for YA (87% versus older adults 72%; P = 0·029). On multivariate analysis, age <40 years, low FLIPI score and observation as initial management were favourable prognostic factors for OS and CSS. We conclude that YA with FL have a favourable prognosis compared to older patients; whether this reflects competing mortality risks or age‐related differences in lymphoma biology warrants further investigation.
Comprehensive transcriptomic analysis of molecularly targeted drugs in cancer for target pathway evaluation
Authors: Mashima Tetsuo , Ushijima Masaru , Matsuura Masaaki , Tsukahara Satomi , Kunimasa Kazuhiro , Furuno Aki , Saito Sakae , Kitamura Masami , Soma‐Nagae Taeko , Seimiya Hiroyuki , Dan Shingo , Yamori Takao , Tomida Akihiro
Published: April 2015

Targeted therapy is a rational and promising strategy for the treatment of advanced cancer. For the development of clinical agents targeting oncogenic signaling pathways, it is important to define the specificity of compounds to the target molecular pathway. Genome‐wide transcriptomic analysis is an unbiased approach to evaluate the compound mode of action, but it is still unknown whether the analysis could be widely applicable to classify molecularly targeted anticancer agents. We comprehensively obtained and analyzed 129 transcriptomic datasets of cancer cells treated with 83 anticancer drugs or related agents, covering most clinically used, molecularly targeted drugs alongside promising inhibitors of molecular cancer targets. Hierarchical clustering and principal component analysis revealed that compounds targeting similar target molecules or pathways were clustered together. These results confirmed that the gene signatures of these drugs reflected their modes of action. Of note, inhibitors of oncogenic kinase pathways formed a large unique cluster, showing that these agents affect a shared molecular pathway distinct from classical antitumor agents and other classes of agents. The gene signature analysis further classified kinome‐targeting agents depending on their target signaling pathways, and we identified target pathway‐selective signature gene sets. The gene expression analysis was also valuable in uncovering unexpected target pathways of some anticancer agents. These results indicate that comprehensive transcriptomic analysis with our database (http://scads.jfcr.or.jp/db/cs/) is a powerful strategy to validate and re‐evaluate the target pathways of anticancer compounds.
Phase I study of OPB‐51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies
Authors: Ogura Michinori , Uchida Toshiki , Terui Yasuhito , Hayakawa Fumihiko , Kobayashi Yukio , Taniwaki Masafumi , Takamatsu Yasushi , Naoe Tomoki , Tobinai Kensei , Munakata Wataru , Yamauchi Takeshi , Kageyama Akiko , Yuasa Miyuki , Motoyama Masaaki , Tsunoda Takeshi , Hatake Kiyohiko
Published: April 2015

We carried out a multicenter dose‐escalation phase I study of oral OPB‐51602, a signal transducer and activator of transcription 3 phosphorylation inhibitor, in patients with relapsed or refractory hematological malignancies to evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary antitumor activity. Twenty patients were treated with OPB‐51602 at doses of 1, 2, 3, 4, and 6 mg in the “3 + 3” dose escalation design. The most common treatment‐related adverse events included nausea (55%), peripheral sensory neuropathy (45%), and diarrhea (40%). The most frequently observed grade 3 or 4 drug‐related adverse events were neutropenia (20%), leukopenia (15%), lymphopenia (10%), and thrombocytopenia (10%). The MTD was 6 mg, with dose‐limiting toxicities of grade 3 lactic acidosis and increased blood lactic acid levels observed in one of three patients and grade 1–2 peripheral neuropathy in three of three patients. The recommended dose was determined to be 4 mg. OPB‐51602 was rapidly absorbed, and exposure tended to increase in a dose‐dependent manner. Accumulation of OPB‐51602 was seen with 4 weeks of multiple treatments. No clear therapeutic response was observed. Durable stable disease was observed in two patients with acute myeloid leukemia and one with myeloma. In conclusion, the MTD of OPB‐51602 was 6 mg. OPB‐51602 was safe and well tolerated in a dose range of 1–4 mg. However, long‐term administration at higher doses was difficult with the daily dosing schedule, and no response was seen. Therefore, further clinical development of OPB‐51602 for hematological malignancies with a daily dosing schedule was terminated.
Individual Differences in Environmental Sensitivity
Authors: Pluess Michael
Published: April 2015

A fundamental trait found in most organisms is the ability to register, process, and respond to external factors. Although such environmental sensitivity is critical for adapting successfully to contextual conditions, individuals tend to differ in their sensitivity to the environment, with some more sensitive than others. Such differences in environmental sensitivity can be seen across many species, including humans. Although the notion of variability in environmental sensitivity is reflected indirectly in many traditional concepts of human psychology, several new frameworks address individual differences in environmental sensitivity more directly and from a perspective of developmental and evolutionary theory. In this article, I integrate these perspectives into a broad meta‐framework before proposing ideas for research on individual differences in environmental sensitivity. I also emphasize that inter‐individual variability in environmental sensitivity be considered in both theoretical and applied work.
Adverse Consequences of School Mobility for Children in Foster Care: A Prospective Longitudinal Study
Authors: Pears Katherine C. , Kim Hyoun K. , Buchanan Rohanna , Fisher Philip A.
Published: April 2015

Few prospective studies have examined school mobility in children in foster care. This study described the school moves of 86 such children and 55 community comparison children (primarily Caucasian), living in a medium‐sized metropolitan area in the Pacific Northwest who were approximately 3 to 6 years old at the study start. Additionally, the effects of moves from kindergarten through Grade 2 on academic and socioemotional competence in Grades 3 through 5 were examined. A greater number of early school moves was associated with poorer later socoemotional competence and partially mediated the effects of maltreatment and out‐of‐home placement on socioemotional competence. This was the case only for children with poorer early learning skills in kindergarten. Implications for preventive intervention are discussed.
Bidirectionality in Self‐Regulation and Expressive Vocabulary: Comparisons Between Monolingual and Dual Language Learners in Preschool
Authors: Bohlmann Natalie L. , Maier Michelle F. , Palacios Natalia
Published: April 2015

Significant differences in language and self‐regulation skills exist among children when they enter formal schooling. Contributing to these language differences is a growing population of dual language learners (DLLs) in the United States. Given evidence linking self‐regulatory processes and language development, this study explored bidirectional associations between English expressive vocabulary and self‐regulation skills for monolingual English and DLL preschool children (N = 250) from mixed‐income families in Los Angeles. Across three time points, findings provide initial support for bidirectionality between these developing skills for both monolinguals and DLLs. Results provide strong empirical support for vocabulary serving as a leading indicator of self‐regulation skills in preschool. Findings also suggest that early self‐regulation skills play a particularly important role for vocabulary development.
Targeted IgA Fc receptor I (FcαRI) therapy in the early intervention and treatment of pristane-induced lupus nephritis in mice
Authors: Liu C , Kanamaru Y , Watanabe T , Tada N , Horikoshi S , Suzuki Y , Liu Z , Tomino Y
Published: April 2015

The Fc receptor I for IgA (FcαRI) down-regulates humoral immune responses and modulates the risk of autoimmunity. This study aimed to investigate whether FcαRI targeting can affect progression of pristine-induced lupus nephritis. In the first experiment (early intervention), four groups of animals were evaluated: untreated FcαRI/FcRγ transgenic (Tg) mice and Tg mice administered control antibody (Ctr Fab), saline and anti-FcαRI Fab [macrophage inflammatory protein (MIP)-8a], respectively, three times a week for 29 weeks, after being injected once intraperitoneally with 0·5 ml pristane. In the second experiment, antibody injection started after the onset of nephritis and was carried out for 2 months, with similar groups as described above. MIP-8a improved proteinuria, decreased the amounts of glomerular injury markers, serum interleukin (IL)-6, IL-1 and monocyte chemoattractant protein (MCP)-1, and F4/80 macrophages in the interstitium and glomeruli, in both experiments. When MIP-8a was used as early intervention, a decrease in mouse serum anti-nuclear antibody (ANA) titres and reduced deposition of immunoglobulins in glomeruli were observed. This effect was associated with reduced serum titres of immunoglobulin (Ig)G2a but not IgG1, IgG2b and IgG3. Furthermore, pathological analysis showed lower glomerular activity index and less fibronectin in MIP-8a treated mice. This study suggests that FcαRI targeting could halt disease progression and lupus activation by selective inhibition of cytokine production, leucocyte recruitment and renal inflammation. Our findings provide a basis for the use of FcαRI as a molecular target for the treatment of lupus.
A fully digital approach to replicate peri‐implant soft tissue contours and emergence profile in the esthetic zone
Authors: Monaco Carlo , Evangelisti Edoardo , Scotti Roberto , Mignani Giuseppe , Zucchelli Giovanni
Published: April 2015

Objective

This short communication reports on a novel digital technique designated – the “Fully Digital Technique (FDT)” – to take the impression of the peri‐implant soft tissue and emergence profile with an intraoral scanner, digitally capturing both the three dimensional position of the implant platform and the coronal and gingival parts of the provisional retained restoration.

Materials and methods

A first intraoral digital impression, which generated a standard triangulation language file (STL1), was taken using a standardized implant scanbody to detect the position of the implant. A second digital impression (STL2) with the provisional retained restoration in situ was performed in two steps: the first part of the scan captured all details of the vestibular and palatal sides of the provisional retained restoration and the adjacent teeth. The provisional retained restoration was then unscrewed, and the subgingival part of the restoration was scanned directly out of the mouth to determine its subgingival shape. STL1 and STL2 were imported into imaging software and superimposed using the “best fit” algorithm to achieve a new merged file (STL3) with the 3D implant position, the peri‐implant mucosa, and emergence profile. The merged file was used to design the CAD/CAM customized abutment and to realize a stereolithographic model by 3D printing.

Results

The STL superimposition of digital impressions of the implant position and the provisional retained restoration constitute a novel technique to obtain a single STL file with the implant position and its peri‐implant mucosal architecture.

Conclusions

FDT is a rapid digital approach for achieving all information of the peri‐implant soft tissue and emergence profile directly from the provisional retained restoration.
Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1‐associated cancer susceptibility syndrome
Authors: Marušić Zlatko , Buljan Marija , Busam Klaus J.
Published: April 2015

Background

Multiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms.

Methods

We report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1‐associated cancer susceptibility syndrome.

Results

The neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up.

Conclusions

We report two new cases of melanoma arising in a BAP1‐deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1‐deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions.
Safety and efficacy of once‐weekly dulaglutide versus sitagliptin after 2 years in metformin‐treated patients with type 2 diabetes (AWARD‐5): a randomized, phase III study
Authors: Weinstock R. S. , Guerci B. , Umpierrez G. , Nauck M. A. , Skrivanek Z. , Milicevic Z.
Published: April 2015

Aims

To compare the once‐weekly glucagon‐like peptide‐1 (GLP‐1) receptor dulaglutide with the dipeptidyl peptidase‐4 (DPP‐4) inhibitor sitagliptin after 104 weeks of treatment.

Methods

This AWARD‐5 study was a multicentre, double‐blind trial that randomized participants to dulaglutide (1.5 or 0.75 mg) or sitagliptin 100 mg for 104 weeks or placebo (reported separately) for 26 weeks. Change in glycated haemoglobin (HbA1c) concentration from baseline was the primary efficacy measure. A total of 1098 participants with HbA1c concentrations ≥7.0% (≥53.0 mmol/mol) and ≤9.5% (≤80.3 mmol/mol) were randomized, and 657 (59.8%) completed the study. We report results for dulaglutide and sitagliptin at the final endpoint.

Results

Changes in HbA1c at 104 weeks were (least squares mean ± standard error) −0.99 ± 0.06% (−10.82 ± 0.66 mmol/mol), −0.71 ± 0.07% (−7.76 ± 0.77 mmol/mol) and −0.32 ± 0.06% (−3.50 ± 0.66 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg and sitagliptin, respectively (p < 0.001, both dulaglutide doses vs sitagliptin). Weight loss was greater with dulaglutide 1.5 mg (p < 0.001) and similar with 0.75 mg versus sitagliptin (2.88 ± 0.25, 2.39 ± 0.26 and 1.75 ± 0.25 kg, respectively). Gastrointestinal adverse events were more common with dulaglutide 1.5 and 0.75 mg versus sitagliptin (nausea 17 and 15% vs 7%, diarrhoea 16 and 12% vs 6%, vomiting 14 and 8% vs 4% respectively). Pancreatic, thyroid, cardiovascular and hypersensitivity safety were similar across groups.

Conclusions

Dulaglutide doses provided superior glycaemic control and dulaglutide 1.5 mg resulted in greater weight reduction versus sitagliptin at 104 weeks, with acceptable safety.
Patterns of niche filling and expansion across the invaded ranges of an Australian lizard
Authors: Tingley Reid , Thompson Michael B. , Hartley Stephen , Chapple David G.
Published: April 2015

Studies of realized niche shifts in alien species typically ignore the potential effects of intraspecific niche variation and different invaded‐range environments on niche lability. We incorporate our detailed knowledge of the native‐range source populations and global introduction history of the delicate skink Lampropholis delicata to examine intraspecific variation in realized niche expansion and unfilling, and investigate how alternative niche modelling approaches are affected by that variation. We analyzed the realized niche dynamics of L. delicata using an ordination method, ecological niche models (ENMs), and occurrence records from 1) Australia (native range), 2) New Zealand, 3) Hawaii, 4) the two distinct native‐range clades that were the sources for the New Zealand and Hawaii introductions, and 5) the species’ global range (including Lord Howe Island, Australia). We found a gradient of realized niche change across the invaded ranges of L. delicata: niche stasis on Lord Howe Island, niche unfilling in New Zealand (16%), and niche unfilling (87%) and expansion (14%) in Hawaii. ENMs fitted to native‐range data generally identified suitable climatic conditions at sites where the species has established non‐native populations, whereas ENMs based on native‐range source clades and non‐native populations had lower spatial transferability. Our results suggest that the extent to which realized niches are maintained during invasion does not depend on species‐level traits. When realized niche shifts are predominately due to niche unfilling, fully capturing species’ responses along climatic gradients by basing ENMs on native distributions may be more important for accurate invasion forecasts than incorporating phylogenetic differentiation, or integrating niche changes in the invaded range.
The downward spiral: eco‐evolutionary feedback loops lead to the emergence of ‘elastic’ ranges
Authors: Kubisch Alexander , Winter Anna‐Marie , Fronhofer Emanuel A.
Published: April 2015

In times of severe environmental changes and resulting shifts in the geographical distribution of animal and plant species it is crucial to unravel the mechanisms responsible for the dynamics of species’ ranges. Without such a mechanistic understanding, reliable projections of future species distributions are difficult to derive. Species’ ranges may be highly dynamic. One particularly interesting phenomenon is range contraction following a period of expansion, referred to as ‘elastic’ behaviour. It has been proposed that this phenomenon occurs in habitat gradients, which are characterized by a negative cline in selection for dispersal from the range core towards the margin, as one may find, for example, with increasing patch isolation. Using individual‐based simulations and numerical analyses we show that Allee effects are an important determinant of range border elasticity. If only intra‐specific processes are considered, Allee effects are even a necessary condition for ranges to exhibit elastic behavior. The eco‐evolutionary interplay between dispersal evolution, Allee effects and habitat isolation leads to lower colonization probability and higher local extinction risk after range expansions, which result in an increasing amount of marginal sink patches and consequently, range contraction. We also demonstrate that the nature of the gradient is crucial for range elasticity. Gradients which do not select for lower dispersal at the margin than in the core (especially gradients in patch size, demographic stochasticity and extinction rate) do not lead to elastic range behavior. Thus, we predict that range contractions are likely to occur after periods of expansion for species living in gradients of increasing patch isolation, which suffer from Allee effects.
Validation of the composite autonomic symptom scale 31 (COMPASS‐31) in patients with and without small fiber polyneuropathy
Authors: Treister R. , O'Neil K. , Downs H. M. , Oaklander A. L.
Published: April 2015

Background and purpose

The recently developed composite autonomic symptom score 31 (COMPASS‐31) is a questionnaire that assess symptoms of dysautonomia. It was distilled from the well‐established Autonomic Symptom Profile questionnaire. COMPASS‐31 has not yet been externally validated. To do so, its psychometric properties and convergent validity in patients with and without objective diagnosis of small fiber polyneuropathy (SFPN) were assessed.

Methods

Internal validity and reliability of COMPASS‐31 were assessed in participants with or without SFPN spanning the full range of severity of autonomic symptoms. Convergent validity was assessed by comparing results of the COMPASS‐31 with the “gold standard” autonomic function testing that measures cardiovagal, adrenergic and sudomotor functions. Additionally, relationships between COMPASS‐31 and the Short Form McGill Pain Questionnaire, Short Form Health Survey and 0–10 numeric pain scale were measured. COMPASS‐31 and all other questionnaire results were compared between patients with or without evidence of SFPN, objectively confirmed by distal‐leg PGP9.5‐immunolabeled skin biopsy.

Results

Amongst 66 participants (28 SFPN+, 38 SFPN−), COMPASS‐31 total scores had excellent internal validity (Cronbach's α = 0.919), test–retest reliability (rs = 0.886; P < 0.001) and good convergent validity (rs = 0.474; P < 0.001). COMPASS‐31 scores differed between subjects with or without SFPN (Z = −3.296, P < 0.001) and demonstrated fair diagnostic accuracy. Area under the Receiver Operating Characteristic curve was 0.749 (P = 0.01, 95% confidence interval 0.627–0.871).

Conclusions

COMPASS‐31 has good psychometric properties in the population of patients being evaluated for SFPN and thus it might be useful as an initial screening tool for the more expensive SFPN objective tests.
Resilience of mollusc communities of the River Saone (eastern France) and its two main tributaries after the 2003 heatwave
Authors: Mouthon Jacques , Daufresne Martin
Published: April 2015

Global climate change can increase the mean and variability of temperature and may increase the occurrence of extremes such as heatwaves. Both gradual and abrupt warming may perturb freshwater communities, but understanding of ecological resilience to such events is limited.

We report the response of mollusc communities in the River Saone and its two main tributaries to the European heatwave of 2003 and determine the extent of community recovery over 8 years following this rare extreme event, during a period of gradual warming.

The 2003 heatwave had a major impact on the density and species richness of mollusc communities across the study area. After the heatwave, abiotic conditions favoured recolonisation by molluscs, yet full recovery of community states (defined as the combination of structure × density × species richness) was not observed at any site.

Given the profound changes observed in the mollusc community structure in the Saone River and in its two main tributaries and the observed slow pace of recovery relative to that observed elsewhere for pulse disturbances (typically < 3 years), we suggest that global change, including warming, may preclude community recovery from pulse disturbances, such as extreme events, and instead yield communities comprising new combinations of species.
Spatial variation in periphyton fatty acid composition in subtropical streams
Authors: Guo Fen , Kainz Martin J. , Sheldon Fran , Bunn Stuart E.
Published: April 2015

Benthic algae play an important role in many stream food webs, not only serving as a major carbon source but also influencing energy transfer as the primary source of polyunsaturated fatty acids (PUFA). Dietary deficiency inPUFAcan limit animal growth and reproduction. AlgalPUFAcontent can vary considerably in response to abiotic factors.

We conducted a field investigation in streams in South‐East Queensland, Australia, to identify environmental factors affecting the fatty acid composition of periphyton.

Riparian canopy cover andNOx‐Nconcentrations explained most of the observed variation in periphyton fatty acid profiles.NOx‐Nconcentrations showed negative relationships with most saturated fatty acids (SAFA), while mono‐unsaturated fatty acids (MUFA) and the fatty acids 16:0 and 16:1ω7 were negatively correlated with canopy cover. In contrast, the percentage of highly unsaturated fatty acids (HUFA) in periphyton was greater with increasing canopy cover regardless ofNOx‐Nconcentrations.

Variation in riparian canopy cover and nutrients gave rise to opposite outcomes in terms of periphyton food quality and quantity. The highest periphyton food quality, measured byHUFAcontent, occurred in streams with high canopy cover and low nutrients, while the highest periphyton food quantity occurred in streams with low canopy cover.

Our study suggests that changes in riparian vegetation and/or nutrient inputs can significantly alter the fatty acid content of periphyton, with important implications for aquatic consumers. We recommend that future studies on impacts of riparian clearing or nutrient enrichment in stream ecosystems place more attention on the effects of food quality rather than quantity.
Are Depressive Symptomatology, Self‐Efficacy, and Perceived Social Support Related to Disability and Quality of Life in Patients With Chronic Migraine Associated to Medication Overuse? Data From a Cross‐Sectional Study
Authors: D'Amico Domenico , Grazzi Licia , Bussone Gennaro , Curone Marcella , Di Fiore Paola , Usai Susanna , Leonardi Matilde , Giovannetti Ambra Mara , Schiavolin Silvia , Raggi Alberto
Published: April 2015

Background

Chronic migraine with medication overuse (CM‐MO) impairs quality of life (QoL) and causes disability. Psychosocial variables such as depressive symptomatology, self‐efficacy, and social support have been sparingly investigated, and their impact on disability and QoL is unknown.

Methods

Patients with CM‐MO under withdrawal were consecutively enrolled. Standardized measures of disability and QoL were used as outcomes; psychosocial (ie, mood state, self‐efficacy, social support) and clinical (ie, headache frequency and intensity) variables were considered as associated variables. Associations between these variables, disability, and QoL were tested with Pearson's correlations. Hierarchical multiple regression was used to assess the cumulative contribution of psychosocial variables on disability and QoL variation when added to clinical variables.

Results

One hundred ninety‐four patients were enrolled; 82.5% were females and mean age was 43.9. Disability and QoL were moderately or little correlated to clinical and psychosocial variables. Models based on clinical variables explained 7.5‐14.3% of disability and QoL variation, with pain intensity being the only significant predictor; when psychosocial variables were added, the explained variation increased to 21.5‐35.2%, with depressive symptomatology always having independent predictive power and perceived social support having independent predictive power in the regression model over role‐prevention component of QoL.

Conclusions

Adding information on psychosocial variables to headache features improved our ability to understand disability and QoL of CM‐MO patients. We deem that the inclusion of psychosocial variables in standard evaluation protocols may contribute to the global assessment of CM‐MO patients, and eventually to their success in reducing the personal and social impact of this condition. Future longitudinal studies are needed to confirm this hypothesis.
The expression of astrocyte elevated gene‐1 in human non‐small‐cell lung cancer and its relationship with postoperative chemotherapy and radiotherapy
Authors: Lu Shan , Xu Jianyu , Xu Xiangying , Hu Songliu , Li Bin , Li Wenxin
Published: April 2015

Aims

To examine the expression of astrocyte elevated gene‐1 (AEG‐1) in non‐small‐cell lung cancer (NSCLC) and analyse the correlation between AEG‐1 expression and the prognosis of the patients, particularly the relationship between AEG‐1 expression and postoperative chemotherapy and radiotherapy.

Methods

The expression of AEG‐1 was analysed by immunohistochemistry in 225 primary NSCLC specimens and 42 adjacent normal lung tissue specimens. Statistical analyses were performed to evaluate the correlation between AEG‐1 expression and the clinicopathological characteristics of the patients as well as the predictive value of AEG‐1.

Results

The expression of AEG‐1 was associated with the pathological stage (P < 0.001) and lymph node status (P = 0.028). A multivariate analysis indicated that AEG‐1 expression was an independent prognostic factor for both overall survival (OS) and disease‐free survival (DFS). In the postoperative chemotherapy group, the OS (P = 0.014) and DFS (P = 0.009) in the low AEG‐1 expression group were longer than the survival times in the high AEG‐1 expression group. In the postoperative radiotherapy group, the local recurrence‐free survival was significantly shorter in patients whose tumours showed high AEG‐1 expression (P = 0.016).

Conclusions

AEG‐1 expression could be a predictor for OS and DFS in NSCLC patients. Patients with low AEG‐1 expression received the greatest benefit from both postoperative chemotherapy and radiotherapy.
Management of modern agricultural landscapes increases nest predation rates in Black‐tailed Godwits Limosa limosa
Authors: Kentie Rosemarie , Both Christiaan , Hooijmeijer Jos C. E. W. , Piersma Theunis
Published: April 2015

Effective conservation of endangered species requires a solid understanding of the demographic causes of population change. Bird populations breeding on agricultural grasslands have declined because their preferred habitat of herb‐rich meadows has been replaced by grassland monocultures. The timing of agricultural activities in these monocultural grasslands is critical, as they often coincide with the nesting phase of breeding birds. Here, we aim to identify the effect of habitat management and targeted nest protection on nest survival of Black‐tailed Godwits Limosa limosa in the Netherlands, a population that has shown a 70% reduction in breeding population size since the 1970s. To protect nests in monocultures from destruction, farmers are paid to either delay mowing or leave a patch of unmown grass around the nest, a patch which in practice varied in size. In herb‐rich meadows, which are typically managed for bird conservation purposes, mowing occurs after hatching. Nest survival declined as the season advanced, more steeply on monocultures than on meadows. Targeted nest protection was only partially successful, as nest predation was considerably higher on mown grassland monocultures with small unmown patches around the nest than in mown monocultures with large unmown patches and in unmown fields. Increased predator densities over the years have been suggested as an important cause of the trend towards lower nest survival, but here we show that nest survival was higher on herb‐rich meadows than on monocultures, and similar to the 1980s. It thus seems that increased predator densities are an increased threat during the egg stage only if habitat quality is low. High‐quality habitat in the form of herb‐rich meadows therefore provides a degree of protection against predators.
Sensory analysis integrated by palynological and physicochemical determinations plays a key role in differentiating unifloral honeys of similar botanical origins (Myrtaceae honeys from southern Spain)
Authors: Rodríguez Inmaculada , Serrano Salud , Galán‐Soldevilla Hortensia , Piva Giulio , Ubera Jose Luis
Published: April 2015

Myrtaceae honeys produced in Sierra Morena (southern Spain, Andalusia) are obtained from both Eucalyptus camaldulensis and Myrtus communis, and honeys can be easily confused when classified as they come from the same botanical family. The characterisation was intended on the basis of their physicochemical, sensory and palynological properties. Cluster analysis (CA) and principal component analysis (PCA) allowed us to make a distinction between two honey profiles. The first one corresponds to the European sensory profile described for Eucalyptus unifloral honeys. The second profile, which sensory characteristics are absolutely different, has not been previously described. Classification of samples is proposed to be based on their pollen type and content and sensory attributes. Therefore, pollen type and content in E. camaldulensis and M. communis are required to distinguish Eucalyptus honey type from other honeys coming from Myrtaceae family. Sensory analysis identifies honey botanical source as well as palynological analysis: Eucalyptus sensory profile requires over 50% of E. camaldulensis and under 30% of M. communis pollen. Previously undefined sensory profile of myrtle honey is showed under 50% of E. camaldulensis and over 30% of M. communis pollen.
Risk Factors for Ischemic Stroke and its Subtypes in Chinese vs. Caucasians: Systematic Review and Meta-Analysis
Authors: Tsai Chung-Fen , Anderson Niall , Thomas Brenda , Sudlow Cathie L. M.
Published: April 2015

Background

Chinese populations are reported to have a different distribution of ischemic stroke subtypes compared with Caucasians.

Aims

To understand this better, we aimed to evaluate the differences in prevalence of risk factors in ischemic stroke and their distributions among ischemic stroke subtypes in Chinese vs. Caucasians.

Summary or review

We systematically sought studies conducted since 1990 with data on frequency of risk factors among ischemic stroke subtypes in Chinese or Caucasians. For each risk factor, we calculated study-specific and random effects pooled estimates in Chinese and Caucasians separately for: prevalence among ischemic stroke; odds ratios, comparing prevalence for each ischemic stroke subtype vs. all others. We included seven studies among 16 199 Chinese, and eleven among 16 189 Caucasian ischemic stroke patients. Risk factors studied were hypertension, diabetes, atrial fibrillation, ischemic heart disease, hypercholesterolemia, smoking and alcohol. Chinese ischemic stroke patients had younger onset of stroke than Caucasians, similar prevalence of hypertension, diabetes, smoking and alcohol, and significantly lower prevalence of atrial fibrillation, ischemic heart disease and hypercholesterolemia. Risk factor associations with ischemic stroke subtypes were mostly similar among Chinese and Caucasian ischemic stroke patients. Compared with all other ischemic subtypes, diabetes was more common in large artery stroke, atrial fibrillation and ischemic heart disease in cardioembolic stroke, and hypertension and diabetes in lacunar stroke.

Conclusion

Our study showed a lower prevalence of atrial fibrillation, ischemic heart disease and hypercholesterolemia in Chinese, and mostly similar risk factor associations in Chinese and Caucasian ischemic stroke patients. Further analyses of individual patient data to allow adjustment for confounders are needed to confirm and extend these findings.