bluuebunny/crossref_metadata_2025 huggingface dataset:
Leveling the Playing Field in Homozygosity Mapping Using Map Distances
Authors: Li Yi , Cagirici Halise Busra , Horpaopan Sukanya , Ott Jurg , Imai Atsuko , Majewski Jacek , Lathrop Mark
Published: July 2015

Studies of linkage disequilibrium (LD) and its variation in the genome are of central importance for understanding evolutionary history, population structure, and selective sweeps. Extreme forms of the latter may result in runs of homozygosity (ROH). In human gene mapping, long ROHs are the basis for homozygosity mapping (HM) with length measured in terms of Mb (106base pairs physical distance). LD varies greatly over the human genome so that long ROHs tend to occur preferentially in regions of high LD and ROHs of the same length in different regions are not strictly comparable. Thus, in human gene mapping, LD appears as a confounder that needs to be taken into account in the interpretation of ROHs. The effect of varying LD can be mitigated by working on a scale of centimorgans (cM, genetic distance) instead of Mb. We demonstrate this effect for HapMap 3 data on chromosome 19 and show examples with different ROH lengths depending on whether physical or genetic lengths are used. These results suggest that HM should preferably be done on genetic rather than physical distances.
Defect‐specific rectocele repair: medium‐term anatomical, functional and subjective outcomes
Authors: Guzmán Rojas Rodrigo , Kamisan Atan Ixora , Shek Ka Lai , Dietz Hans Peter
Published: July 2015

Background

Rectocele is a herniation of the anterior wall of the rectal ampulla through a defect in the rectovaginal septum causing protrusion of the posterior vaginal wall. Common symptoms include symptoms of prolapse and obstructed defecation.

Aims

To describe subjective, anatomical and functional results of defect‐specific rectocele repair.

Materials and Methods

This is an internal audit of 137 women who underwent defect‐specific rectocele repair. Pre‐ and post‐operative assessment included a standardised interview, clinical examination and 3D/4D transperineal ultrasound. Outcome measures were symptoms of obstructed defecation, recurrent prolapse symptoms, clinical posterior compartment recurrence and rectocele recurrence on ultrasound.

Results

At a mean follow‐up of 1.4 years, 117 (85%) of women considered themselves cured or improved. Thirty‐four (25%) complained of recurrent prolapse symptoms and 47 (34%) symptoms of obstructed defecation, a significant reduction (P < 0.0001). Clinical recurrence (Bp ≥ −1) was seen in 19 women (14%) and recurrence on ultrasound in 27 (20%). The mean depth of recurrence was 16.6 mm (10.3–25.1). We tested multiple potential predictors of recurrence, including age, BMI, vaginal parity, previous hysterectomy and/or prolapse surgery, follow‐up time, pre‐operative clinical and ultrasound findings. Only hiatal area on Valsalva (OR 0.95 for sonographic recurrence, P = 0.01) and enterocele (for clinical and sonographic recurrence, OR 4.03, P = 0.01 and OR 2.72, P = 0.02, respectively) reached significance.

Conclusion

Defect‐specific rectocele repair is effective both in restitution of normal anatomy and in resolving prolapse and obstructed defecation symptoms at a mean follow‐up of 1.4 years.
Usefulness of early post‐operative liver function test monitoring after laparoscopic common bile duct exploration
Authors: Wewelwala Chandika , Cashin Paul , Berry Roger , Blamey Stephen , Jones Gregory E. , Croagh Daniel G.
Published: July 2015

Background

This study examines the usefulness of early post‐operative liver function test (LFT) monitoring in predicting retained choledocholithiasis after laparoscopic common bile duct exploration (LCBDE).

Methods

Data on patients who had LCBDE over a 3‐year period were collected retrospectively. Patients who had ongoing choledocholithiasis after unsuccessful LCBDE were considered for the test group and patients who had successful LCBDE were considered for the control group. Preoperative, day 1 post‐operative and day 2 post‐operative alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), alanine transaminase (ALT) and bilirubin levels were recorded. Proportions of patients who had worsening LFTs were analysed in each group.

Results

Proportions of patient who had worsening LFTs on day 1 were not statistically different between two groups and they were statistically equal on equivalence testing (two one‐sided tests). On day 2, proportions of patient were again not statistically different. Bilirubin and ALT were statistically equivalent (P = 0.022 and P = 0.025 respectively) but GGT and ALP failed to achieve statistical equivalence (P = 0.062 and P = 0.138 respectively) on day 2. Twelve patients with normal appearing final intraoperative cholangiogram needed reintervention due to retained choledocholithiasis diagnosed subsequently. LFTs progressively improved despite presence of choledocholithiasis in eight of these 12 patients (75%) and only four were diagnosed by worsening post‐operative LFTs during index admission.

Conclusion

LFTs in the early post‐operative period are not useful in determining which patients require biliary imaging or intervention after an apparently successful LCBDE.
Cervical spine immobilization following blunt trauma: a systematic review of recent literature and proposed treatment algorithm
Authors: Lukins Timothy R. , Ferch Richard , Balogh Zsolt J. , Hansen Mitchell A.
Published: July 2015

Background

Management of the cervical spine following blunt trauma is commonplace. In 2013, the American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) published practice guidelines drawn from evidence dating to 2011. Since then, further publications have emerged that are reviewed, and a simple management algorithm produced to assist practitioners in Australian trauma centres. These publications attempt to shed light on two controversial scenarios, those being the management of symptomatic patients with negative computed tomography (CT) and management of the obtunded patient.

Methods

The search strategy mirrored that of the AANS/CNS guidelines. A search of the National Library of Medicine (PubMed) database for manuscripts published between January 2011 and October 2014 was conducted. One reviewer extracted data from studies assessing the performance of various imaging modalities in identifying traumatic cervical spine injuries. In clinical scenarios where little evidence has emerged since the AANS/CNS guidelines, key manuscripts published prior to 2011 were identified from bibliographies.

Results

Awake, asymptomatic patients may be ‘cleared’ without further imaging. Awake, symptomatic patients without pathology on CT and without neurological deficit can safely be ‘cleared’ without magnetic resonance imaging. There is no longer a role for flexion–extension films. In the obtunded patient, findings remain conflicting.

Conclusion

Several of these findings represent a departure from previous practices, including clearance of patients with non‐neurological symptoms on the basis of CT and the exclusion of flexion–extension film in detecting injury. Management of the obtunded patient remains controversial.
Synchronous liver resection with cytoreductive surgery for the treatment of liver and peritoneal metastases from colon cancer: results from an Australian centre
Authors: Alzahrani Nayef , Ung Lawson , Valle Sarah J. , Liauw Winston , Morris David L.
Published: July 2015

Background

Treatment of peritoneal metastases (PM) and liver metastases (LM) from colon cancer remains controversial. LM has been viewed as exclusion criterion for cytoreductive surgery (CRS) on the basis that such spread represents systemic disease. CRS and intraperitoneal chemotherapy (IPC) has gained increasing recognition as a treatment modality for selected patients with colon cancer and PM. This study analyses results of CRS and IPC for colon cancer and synchronous resection for treatment of LM and PM.

Methods

Seventy‐eight patients with PM/LM colon cancer were analysed. Forty‐two patients with PM were treated for disease limited to the peritoneum (A), and 36 patients received treatment for both PM and LM (B). Overall survival (OS), disease‐free survival (DFS), morbidity, mortality and recurrence were compared.

Results

Median OS and DFS was 32.8 and 13.5 months. The median OS for A and B were 45.5 and 24.4 months respectively. Within B patients, 18 had a peritoneal carcinomatosis index (PCI) >7 and >3 LM and median survival of 21.8 months compared with 18 patients with PCI ≤7 and LM ≤3 with median survival of 38.4 months. Median DFS for A and B were 17.7 and 8.5 months respectively. Twenty‐seven in total experienced major complications following surgery. Sixty‐one patients recurred. Of A, 71.4% recurred compared with B at 86.1%.

Conclusion

While our study is limited, it has demonstrated encouraging evidence that long‐term survival outcomes can be achieved in this small but significant number of patients treated by CRS/IPC and additional synchronous liver resection with no significant increase in morbidity when compared with CRS/IPC alone.
Serum Metabolomic Profiling of Sulphur Mustard‐Exposed Individuals Using 1HNuclear Magnetic Resonance Spectroscopy
Authors: Zamani Zahra , Ghanei Mostafa , Panahi Yunus , Arjmand Mohammad , Sadeghi Sedigheh , Mirkhani Fatemeh , Parvin Shahram , Salehi Maryam , Sahebkar Amirhossein , Vahabi Farideh
Published: July 2015

Sulphur mustard is an alkylating agent that reacts with different cellular components, causing acute and delayed complications that may remain for decades after exposure. This study aimed to identify differentially expressed metabolites between mustard‐exposed individuals suffering from chronic complications compared with unexposed individuals as the control group. Serum samples were obtained from 15 mustard‐exposed individuals and 15 apparently healthy unexposed individuals. Metabolomic profiling was performed using 1H nuclear magnetic resonance spectroscopy, and analyses were carried out using Chenomex and MATLAB softwares. Metabolites were identified using Human Metabolome Database, and the main metabolic pathways were identified using MetaboAnalyst software. Chemometric analysis of serum samples identified 11 differentially expressed metabolites between mustard‐exposed and unexposed groups. The main pathways that were influenced by sulphur mustard exposure were related to vitamin B6 (down‐regulation), bile acid (up‐regulation) and tryptophan (down‐regulation) metabolism. Metabolism of vitamin B6, bile acids and tryptophan are the most severely impaired pathways in individuals suffering from chronic mustard‐induced complications. These findings may find implications in the monitoring of exposed patients and identification of new therapeutic approaches.
The state of TRUS biopsy sepsis: readmissions to Victorian hospitals with TRUS biopsy‐related infection over 5 years
Authors: Roth Hedley , Millar Jeremy L , Cheng Allen C , Byrne Amanda , Evans Sue , Grummet Jeremy
Published: July 2015

Objectives

To describe the incidence, morbidity and mortality of men who developed infectious complications requiring hospital admission following TRUS prostate biopsy in Victoria, Australia. Further it aimed to report the financial cost of these admissions.

Subjects & Methods

The Department of Health's Victorian Admitted Episodes Data Set was used to identify those patients who underwent TRUS biopsy in Victoria who were subsequently readmitted within 7 days to any Victorian hospital with infective complications from July 2007 to June 2012. All Victorian public and private hospitals were included. Patients were excluded if their biopsy was performed during a multi‐day admission. Financial costing data was obtained where available from the Department Of Health and Human Services for readmissions with post‐TRUS infection where available and adjusted to 2012 prices. Institutional ethics committee approval was granted for this study.

Results

Thirty‐four thousand eight hundred and sixty‐five TRUS biopsies were performed in the 5‐year period. 1276 (3.66%) were readmitted to a Victorian hospital within 7 days. 604 (1.73%) of these were readmitted with a biopsy‐related infection. No significant trend in sepsis rates was seen in 5 years. The median readmission LOS was 4 days. The total burden of readmissions was 3 686 days over 5 years. One patient readmitted with a biopsy related infection died during that episode of care. 20 051 (57.51%) of biopsies resulted in a diagnosis of prostate cancer. Financial costing data was available for 218 (36%) of infectious readmissions with a mean cost per readmission were $7 362 AUD (£4137 or $6844 USD, 95% CI $6219–8505 AUD) or $1 256 AUD per day.

Conclusion

Infection following TRUS biopsy was associated with a readmission rate for infection of 1 in 57 biopsies, an excess of 3 686 bed days required over 5 years with a cost of $1 256 AUD per day. The rate of infection remained stable for the period examined.
Inequality, Distributive Justice and Political Participation: An Analysis of the Case of Chile
Authors: CASTILLO JUAN C. , PALACIOS DIEGO , JOIGNANT ALFREDO , THAM MAXIMILIANO
Published: July 2015

Political participation has frequently been associated with individual resources; that is, individuals with higher incomes, higher educational levels and more time tend to participate in the political process to a greater extent than other individuals do. The present study suggests that in addition to resources, an individual's beliefs about economic distribution are an important determinant of participation both in elections and in protests. Based on the analysis of the Chilean data from the Latin American Public Opinion Project (LAPOP) 2012, the results suggest that distributive beliefs are associated primarily with participation in protests.
Human norovirus infection and the acute serum cytokine response
Authors: Newman K L , Moe C L , Kirby A E , Flanders W D , Parkos C A , Leon J S
Published: July 2015

Noroviruses (NoV) are the most common cause of epidemic gastroenteritis worldwide. The acute immune response to NoV in humans is poorly understood, hindering research on prevention and treatment. To elucidate the acute immune response and test for cytokine predictors of susceptibility to infection, serum samples from two human NoV challenge studies were tested for 16 cytokines. Subjects who became infected (n = 26) were age-matched with subjects who remained uninfected following NoV challenge (n = 26). Samples were tested from prechallenge and days 1-4 post-challenge. Cytokine responses were compared between infected and uninfected groups. Overall, infected individuals exhibited an elevation in T helper type 1 (Th1) and Th2 cytokines, as well as chemokines interleukin (IL)-8 and monocyte chemoattractant protein (MCP-1), compared to uninfected individuals (all P < 0·05). Most cytokines peaked on day 2 post-challenge in infected subjects, and tumour necrosis factor (TNF)-α, IL-8, and IL-10 remained elevated to day 3. The only cytokine elevated significantly among infected subjects to day 4 post-challenge was IL-10 (P = 0·021). Prechallenge cytokine concentrations were not predictive of infection status post-challenge. There were no significant changes in serum cytokines among NoV-challenged subjects who remained uninfected. These results suggest that NoV infection elicits a Th1-type response, with some Th2 activation. Persistent elevation of IL-10 among infected subjects is consistent with activation of adaptive immune responses, such as B cell expansion, as well as down-regulation of Th1 cytokines. This study presents the first comprehensive description of the acute cytokine response to GI.1 NoV in humans.
In silico analysis of a novel MKRN3 missense mutation in familial central precocious puberty
Authors: Neocleous Vassos , Shammas Christos , Phelan Marie M. , Nicolaou Stella , Phylactou Leonidas A. , Skordis Nicos
Published: July 2015

Background

The onset of puberty is influenced by the interplay of stimulating and restraining factors, many of which have a genetic origin. Premature activation of the GnRH secretion in central precocious puberty (CPP) may arise either from gain‐of‐function mutations of the KISS1 and KISS1R genes or from loss‐of‐function manner mutations of the MKRN3 gene leading to MKRN3 deficiency.

Objective

To explore the genetic causes responsible for CPP and the potential role of the RING finger protein 3 (MKRN3) gene.

Design and patients

We investigated potential sequence variations in the intronless MKRN3 gene by Sanger sequencing of the entire 507 amino acid coding region of exon 1 in a family with two affected girls presented with CPP at the age of 6 and 5·7 years, respectively.

Results

A novel heterozygous g.Gly312Asp missense mutation in the MKRN3 gene was identified in these siblings. The imprinted MKRN3 missense mutation was also identified as expected in the unaffected father and followed as expected an imprinted mode of inheritance. In silico analysis of the altered missense variant using the computational algorithms Polyphen2, SIFT and Mutation Taster predicted a damage and pathogenic alteration causing CPP. The pathogenicity of the alteration at the protein level via an in silico structural model is also explored.

Conclusion

A novel mutation in the MKRN3 gene in two sisters with CPP was identified, supporting the fundamental role of this gene in the suppression of the hypothalamic GnRH neurons.
Mentors' attachment dimensions, the quality of mentoring relationship and protégés' adjustment: a moderated mediation model
Authors: Goldner Limor
Published: July 2015

The relationships between mentors' (n = 168) attachment dimensions, the quality of mentoring relationship and protégés' (n = 187) level of adjustment after 8 months of mentoring intervention were explored. Unexpectedly, protégés of mentors with moderately negative childhood experiences and an insecure state of mind had higher levels of adjustment at the end of mentoring, whereas mentors' positive emotional childhood experiences contributed negatively to levels of adjustment. Furthermore, a dependent mother–protégé relationship moderated the relationship between mentors' attachment anxiety or avoidance and the quality of the relationship, such that it mediated the relationship between mentors' attachment anxiety and avoidance and led to a decrease in protégés' level of adjustment at the end of the intervention. The findings suggest that the disadvantages of a dependent mother–protégé relationship as regard protégés' level of adjustment interact with mentors' avoidance or anxiety, and that there may be an advantage in a mentor–protégé mismatch in terms of an anxious/dependent relational history.
Evolutionary analysis identifies multiple genome expansions and contractions in Sepsidae (Diptera) and suggests targets for future genomic research
Authors: Su Kathy F. Y. , Puniamoorthy Jayanthi , Özsu Nesibe , Srivathsan Amrita , Meier Rudolf
Published: July 2015

We here argue that data from comparative studies of genome size and karyotypes provide important information for planning comparative research on genome evolution. We document for 39 species of sepsids that there is a four‐fold difference in genome size (151–618 Mbp). Mapping genome sizes onto a phylogenetic hypothesis identifies that this range is the result of five genome expansions and four genome contractions that we here define as changes in genome size of more than 50 Mbp. We then generate karyotype data for 10 species and find no changes in chromosome number. The study reveals that the “Oriental” clade of sepsids is a promising system for studying genome evolution because it has experienced three genome expansion events. These events can be compared with an expansion in the “Neotropical” clade in order to reveal the mechanisms that underlie genome expansion in Sepsidae. A review of the literature on genome sizes and karyotypes reveals that they have been poorly documented in Metazoa. This means that researchers interested in the evolution of genome expansions and contractions are currently not being able to identify appropriate target taxa for genome sequencing. We thus argue for more comparative research on genome sizes and karyotypes and point out that historically species were chosen for genome sequencing for reasons not related to genome evolution (e.g. small genome size, model species status, phylogenetic position, interesting phenotypes). We believe that it is now time to use a more genome‐centric selection criterion, where species for whole genome sequencing are selected based on their importance for understanding genome evolution.
Phylogenetic analyses elucidate the inter‐relationships of Pamphilioidea (Hymenoptera, Symphyta)
Authors: Wang Mei , Rasnitsyn Alexandr P. , Li Hu , Shih Chungkun , Sharkey Michael J. , Ren Dong
Published: July 2015

The phylogeny of the superfamily Pamphilioidea is reconstructed using morphology and DNA sequence data of living and fossil taxa by employing two phylogenetic methods (maximum parsimony and Bayesian inference). Based on our results, the monophyly of Pamphilioidea and Pamphiliidae are corroborated, whereas two extinct families, Xyelydidae and Praesiricidae, are not monophyletic. Because members of Praesiricidae together with Megalodontes form a monophyletic group, we propose that the paraphyletic Praesiricidae is synonymized under Megalodontesidae (syn. nov.). The origin of Pamphilioidea is hypothesized to be as early as the Early Jurassic. To better understand morphological evolution in the early lineages of Pamphilioidea, ancestral states of the first flagellomere and the first and second abdominal terga are reconstructed on the morphology‐based tree. In addition, three new genera (Medilyda, Brevilyda, Strenolyda) with five new species (Medilyda procera, M. distorta, Brevilyda provecta, Strenolyda marginalis and S. retrorsa) are described based on well‐preserved xyelydid fossils from the Middle Jurassic Jiulongshan Formation of north‐eastern China.
Evaluation of peri‐implant buccal bone by computed tomography: an experimental study
Authors: González‐Martín Oscar , Oteo Carlos , Ortega Ricardo , Alandez Javier , Sanz Mariano , Veltri Mario
Published: July 2015

Objectives

To evaluate the accuracy of measuring peri‐implant buccal bone when using three different computed tomography devices.

Materials and methods

Sixty tissue‐level or bone‐level dental implants were placed in bovine ribs with either buccal bone full coverage, dehiscence or fenestration. For each site, the distance from the bone defect to the implant neck and the buccal bone thickness 1 mm apical to the crest were measured using a calliper. Subsequently, all sites were scanned in a reproducible position using a multi‐slice computed tomography (CT) (Brightspeed, voxel size 0.625 mm) and two cone‐beam computed tomography devices (i‐CAT NG, voxel size 0.3 mm and Newtom VGi, voxel size 0.2 mm). Bone thickness was measured on images from the three systems similar to direct measurements and differences were evaluated. Factors that could influence the buccal bone identification were assessed by multiple binary logistic regression.

Results

Buccal bone ranged from 0.1 mm to 2.75 mm in thickness and was not visible in 68%, 63% and 60% of cases when using CT, i‐CAT and Newtom, respectively. For each mm of bone thickness increment, the odds of radiographic identification increased by 30.6 (P < 0.001). Bone defects negatively affected radiographic visibility (P < 0.05). All devices underestimated bone dimensions although differences among them were not significant.

Conclusions

Within these experimental conditions, the investigated devices have equivalent low accuracy in diagnosing peri‐implant buccal bone. Accuracy was significantly influenced by buccal bone thickness, especially if <1 mm, and in presence of peri‐implant marginal defects.
Effects of threat management interactions on conservation priorities
Authors: Auerbach Nancy A. , Wilson Kerrie A. , Tulloch Ayesha I.T. , Rhodes Jonathan R. , Hanson Jeffrey O. , Possingham Hugh P.
Published: July 2015

Decisions need to be made about which biodiversity management actions are undertaken to mitigate threats and about where these actions are implemented. However, management actions can interact; that is, the cost, benefit, and feasibility of one action can change when another action is undertaken. There is little guidance on how to explicitly and efficiently prioritize management for multiple threats, including deciding where to act. Integrated management could focus on one management action to abate a dominant threat or on a strategy comprising multiple actions to abate multiple threats. Furthermore management could be undertaken at sites that are in close proximity to reduce costs. We used cost‐effectiveness analysis to prioritize investments in fire management, controlling invasive predators, and reducing grazing pressure in a bio‐diverse region of southeastern Queensland, Australia. We compared outcomes of 5 management approaches based on different assumptions about interactions and quantified how investment needed, benefits expected, and the locations prioritized for implementation differed when interactions were taken into account. Managing for interactions altered decisions about where to invest and in which actions to invest and had the potential to deliver increased investment efficiency. Differences in high priority locations and actions were greatest between the approaches when we made different assumptions about how management actions deliver benefits through threat abatement: either all threats must be managed to conserve species or only one management action may be required. Threatened species management that does not consider interactions between actions may result in misplaced investments or misguided expectations of the effort required to mitigate threats to species.
Repetitive injections of botulinum toxin A continuously increase the duration of efficacy in primary axillary hyperhidrosis: A retrospective analysis in 101 patients
Authors: Brehmer Franziska , Lockmann Anike , Grönemeyer Lisa‐Lena , Kretschmer Lutz , Schön Michael P. , Thoms Kai‐Martin
Published: July 2015

Background and objectives

Botulinum toxin type A is an effective, well‐tolerated, albeit temporary treatment for primary axillary hyperhidrosis. However, little is known about the influence of repetitive injections on the duration of efficacy.

Patients and methods

139 patients with primary axillary hyperhidrosis were injected with 50 units of botulinum toxin per axilla. In 101 patients, who received at least three treatments, the duration of efficacy after the first, second, and last treatment was evaluated.

Results

The median duration of efficacy was 4.0 months, 4.5 months, and 5.0 months after the first, second, and last injection, respectively. Overall, the duration of efficacy was significantly longer after the last injection compared to the duration of efficacy after the first injection (p =  0.0055, Wilcoxon matched‐pairs signed‐rank test). Likewise, the difference between the first and second injection (p =  0.0302) as well as the difference between the second and the last injection (p =  0.0381) were significant. In 25.7 % of patients, the duration of efficacy remained unchanged over the entire treatment period.

Conclusions

Repetitive botulinum toxin treatments led to a significantly increased duration of efficacy in axillary hyperhidrosis. While the average duration of efficacy continued to increase with each treatment, there were considerable interindividual differences.
Complications associated with cutaneous aesthetic procedures
Authors: Hartmann Daniela , Ruzicka Thomas , Gauglitz Gerd G.
Published: July 2015

In recent years, a plethora of novel therapeutic approaches to fight signs of aging and to influence external body appearance have become available in aesthetic dermatology. Extensive research in this field has led to advanced understanding of the anatomy and physiology of the aging face. To successfully address the complex age‐related alterations anti‐aging treatment nowadays calls for a multi‐faceted approach. Most frequently utilized aesthetic procedures include the use of botulinum toxin, a variety of filling substances, microneedling (collagen induction therapy), chemical peeling, lasers, radiofrequency, thread facelift and injectional lipolysis with phosphatidylcholine/deoxycholate among others. Unfortunately, many clinicians still lack in‐depth understanding of potential complications, risk factors and side effects associated with minimal‐invasive procedures. The following review aims to give a broad overview of nowadays most frequently used approaches in the dermato‐aesthetic field and their related complications.
Early fasting glucose measurements can predict later glycaemic response to once weekly dulaglutide
Authors: Grunberger G. , Forst T. , Fernández Landó L. , Pechtner V. , Shaginian R. , Jia N. , Gough S.
Published: July 2015

Aims

To assess whether early measures of fasting blood glucose predict later glycaemic response with once‐weekly dulaglutide in patients with Type 2 diabetes mellitus.

Methods

Post hoc analyses were conducted separately for two phase 3 studies (AWARD–5 and AWARD–1) in patients assigned to once‐weekly dulaglutide. Week 2 fasting blood glucose was used as a predictor variable, and glycaemic treatment response was defined by HbA1c response based on a composite efficacy endpoint. The association between fasting blood glucose and the glycaemic response was analysed using chi‐square tests.

Results

There was a strong association between fasting blood glucose < 7.9 mmol/l at week 2 and achieving the HbA1c composite efficacy endpoint at week 26 (P < 0.01). Higher fasting blood glucose at week 2, however, did not predict absence of glycaemic response and requires further assessment.

Conclusions

Fasting blood glucose measured at 2 weeks may be an early and useful predictor of glycaemic response to once‐weekly dulaglutide treatment.
Glycaemic control and lipid concentrations in a cohort of people with diabetes over 7 years of follow‐up: a regional audit of diabetes care in the UK
Authors: Wainwright P. , Oluwatowoju I. , Ryan A. , Abu E. , Byrne C. D.
Published: July 2015

Aim

To determine changes in glycaemic control and lipids over time since the introduction of the Quality and Outcomes Framework.

Methods

In adults with diabetes (Hampshire, UK), HbA1c and lipid measurements were retrieved from a regional National Health Service biochemical database in 2006 and 2013 and analysed using anova and logistic regression modelling.

Results

In 2006, 8568 people with diabetes were identified. In 2013, 5815 had follow‐up data, 1207 people were lost to follow‐up and 1546 had died. At baseline, HbA1c concentrations were 62.1 ± 16.1, 64.7 ± 16.7 and 64.5 ± 17.6 mmol/mol for those with follow‐up data, those lost to follow‐up and those who died, respectively. The mean age was 60.2 ± 14.5, 57.6 ± 18.0 and 73.9 ± 10.5 years, respectively, for the three groups. Total cholesterol, HDL cholesterol and triglyceride concentrations were similar between groups. The mean HbA1c concentration for those with complete follow‐up data was 62.1 ± 16.1 mmol/mol in 2006 and 61.7 ± 17.3 mmol/mol in 2013. Quality and Outcomes Framework targets for cholesterol (< 5 mmol/l) were achieved by 79% of people in 2006 and 83% in 2013 (P < 0.001). Baseline age and HbA1c were associated with death at follow‐up: the odds ratio per year increase in baseline age was 1.10 (95% CI 1.09–1.10; P < 0.001) and per unit increase in HbA1c it was 1.02 (95% CI 1.02–1.03; P < 0.001).

Conclusions

Glycaemic control showed remarkable stability over 7 years of follow‐up, despite increasing patient age and duration of diabetes. More patients achieved lipid targets in 2013 than in 2006. Although baseline HbA1c was a predictor of death at follow‐up, baseline HbA1c differed little between survivors, non‐survivors and those lost to follow‐up.
Efficacy and safety of once‐weekly glucagon‐like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta‐analysis of randomized controlled trials
Authors: Karagiannis T. , Liakos A. , Bekiari E. , Athanasiadou E. , Paschos P. , Vasilakou D. , Mainou M. , Rika M. , Boura P. , Matthews D. R. , Tsapas A.
Published: July 2015

Aim

To assess the efficacy and safety of recently approved once‐weekly glucagon‐like peptide 1 receptor agonists (GLP‐1 RAs) in patients with type 2 diabetes.

Methods

We conducted a systematic review and meta‐analysis of randomized controlled trials comparing any GLP‐1 RA licensed for once‐weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate.

Results

In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was −0.66% [six studies; 95% confidence interval (CI) −1.14 to −0.19; I2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I2 = 65%) with dulaglutide. Based on data from placebo‐controlled trials, we did not detect statistically significant weight‐sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once‐weekly GLP‐1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c‐lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I2 = 40% and −0.28; 95% CI −0.45 to −0.10; I2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions.

Conclusions

Given their dosing scheme and overall efficacy and safety profile, once‐weekly GLP‐1 RAs are a convenient therapeutic option for use as add‐on to metformin.
Vitamin D deficiency and airflow limitation in the Baltimore Longitudinal Study of Ageing
Authors: Moberg Mia , Elango Palchamy , Ferrucci Luigi , Spruit Martijn A. , Wouters Emiel F. , Rutten Erica P. A.
Published: July 2015

Background

Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD) and has also been linked to comorbidities often present in COPD.

Aim

The aim of this study was to investigate whether vitamin D deficiency was related specifically to airflow limitation or whether vitamin D deficiency was determined by conditions that frequently coexist with COPD: insulin resistance, hypertension, anaemia, obesity and hypercholesterolaemia.

Methods

For this cross‐sectional analysis, we included 897 subjects from the Baltimore Longitudinal Study of Aging. Subjects taking vitamin D supplements were excluded. Airflow limitation was defined as FEV1/FVC < lower limit of normal. Logistic regression was used to assess the association between vitamin D deficiency (25‐hydroxy vitamin D < 20 ng/mL) and possible determinants.

Results

Vitamin D deficiency was not specific for subjects with airflow limitation. Body mass index (BMI) (OR: 1·05, P < 0·03) and obesity (BMI > 30 kg/m2) (OR: 1·9, P < 0·002) were significantly associated with vitamin D deficiency in the adjusted multivariate regression analysis. Physical activity was associated with a decreased risk of vitamin D deficiency.

Conclusions

Airflow limitation was not an independent determinant of vitamin D deficiency. The effect of weight loss and increased physical activity on vitamin D levels should be investigated further in intervention studies.
The evolution of larval developmental mode: insights from hybrids between species with obligately and facultatively planktotrophic larvae
Authors: Armstrong Anne Frances , Lessios Harilaos A.
Published: July 2015

Life history characteristics play a pervasive role in the ecology and evolution of species. Transitions between feeding and non‐feeding larval development have occurred many times in both terrestrial and marine phyla, however we lack a comprehensive understanding of how such shifts occur. The sea biscuits Clypeaster rosaceus and Clypeaster subdepressus employ different life history strategies (facultatively feeding larvae and obligately feeding larvae, respectively) but can hybridize. In this study, we examined the development of hybrid larvae between these two species in order to investigate the inheritance of larval developmental mode. Our results show that both reciprocal hybrid crosses developed via the feeding mode of their maternal species. However, as feeding larvae can obtain both energy and hormones from algal food, we tested how hormones alone affected development by setting up a treatment where we added exogenous thyroid hormone, but no food. In this treatment the offspring of all four crosses (two homospecific and two heterospecific crosses) were able to metamorphose without algal food. Therefore we hypothesize that although hybrid developmental mode was inherited from the maternal species, this result was not solely due to energetic constraints of egg size.
Dental and jaw injuries sustained by hooligans
Authors: Sekulic Michel , Kühl Sebastian , Connert Thomas , Krastl Gabriel , Filippi Andreas
Published: July 2015

Aim

The study deals with fighting‐related dental injuries sustained by hooligans and the influence of wearing a mouthguard on fighting‐related dental trauma.

Material and Methods

From 2012 to 2013, standardized multiple‐choice questionnaires were distributed via contacts in the hooligan scene in Switzerland. The survey was conducted with the guarantee of complete anonymity and investigated injury patterns in hooligans from different age groups, of different nationalities as well as educational and income levels.

Results

Of the 95 hooligans surveyed, 82 had sustained a dental injury: 29 were minor and 53 were severe dental injuries. During violent confrontations, 37 of the 95 hooligans wore a mouthguard. The most commonly used mouthguards were custom‐made (19/37) or boil‐and‐bite (10/37). The use of ready‐made mouthguards without an individualized fit (6/37) was less frequent. Hooligans who wore a boil‐and‐bite or a custom‐made mouthguard lost fewer teeth during fights than participants wearing a mouthguard without an individualized fit (P = 0.056).

Conclusion

The risk of trauma during violent confrontations between hooligans is very high, as expected. The injuries range from dental trauma to bruising, lacerations and even serious bone fractures of the face and the extremities. During violent clashes over a third of the hooligans wear a mouthguard that has usually been custom‐made or at least individually fitted; this is a far higher frequency than for most contact sports.
Olfactory responses of western flower thrips (Frankliniella occidentalis) populations to a non‐pheromone lure
Authors: Nielsen M‐C. , Worner S.P. , Rostás M. , Chapman R.B. , Butler R.C. , de Kogel W.J. , Teulon D.A.J.
Published: July 2015

Western flower thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), is a major pest of horticultural crops worldwide. The search for alternative pest management techniques has resulted in increasing interest in the use of kairomones and other behaviour‐modifying chemicals to mitigate the impact of this pest. In this study, we determined whether the origin of populations, feeding history, and/or genotype influence the response of WFT to the thrips kairomone lure methyl isonicotinate (MI) in a Y‐tube olfactometer study. Four New Zealand thrips populations were tested: (1) from a commercial glasshouse capsicum crop, (2) from a long‐established laboratory colony (>222 generations) kept on chrysanthemums, (3) from a laboratory colony (6–9 generations) kept on French dwarf beans, and (4) thought to be a separate cryptic non‐pest species from outdoor yellow tree lupins, Lupinus arboreus Sims (Fabaceae). In the laboratory tests, significantly more WFT from all four populations chose the MI‐laden arm of a Y‐tube olfactometer when it contained 1 μl methyl isonicotinate (61.3–73.2%) compared with the blank no‐odour arm. No differences in response to MI were found between the two laboratory and the one glasshouse WFT populations. Both laboratory populations and the greenhouse population belonged to the ‘glasshouse pest’ genotype of WFT. However, the cryptic non‐pest WFT genotype responded more strongly to MI than any of the other populations, although the response was only significantly stronger than that of the long‐established laboratory population. Significant differences were also found among populations in the average time taken for thrips to make a choice to enter either arm of the Y‐tube olfactometer, with the cryptic non‐pest lupin genotype taking the shortest time, followed by thrips from the capsicum glasshouse. The results are discussed with respect to the variability in olfactory perception and olfactory behaviour within a species and the relevance to the use of such a kairomone lure in pest management programmes.
Metal hyperaccumulation in Brassicaceae mediates defense against herbivores in the field and improves growth
Authors: Kazemi‐Dinan A. , Barwinski A. , Stein R.J. , Krämer U. , Müller C.
Published: July 2015

Several Brassicaceae species are able to hyperaccumulate extraordinarily high levels of heavy metals in their aboveground tissues. This rare and complex trait named metal hyperaccumulation may offer effective protection against antagonists. Several laboratory studies provide evidence that metal hyperaccumulation acts as an elemental defense. Here, we investigated whether this elemental defense can be confirmed in the field and whether plant growth is affected when plants can hyperaccumulate metals from the soil. Plants of Arabidopsis halleri (L.) O'Kane & Al‐Shehbaz, which can hyperaccumulate cadmium (Cd) and zinc (Zn), were cultivated in pots in unamended (control) or metal‐amended soil (test) for 2 months. The pots containing the plants were then transferred to a common garden. Leaf‐damaging insect visitors were monitored over a period of 3 months. Plant size and shoot mass were measured directly before and at the end of the field exposure. Furthermore, before and at the end of the field exposure we determined leaf concentrations of Cd and Zn, as well as glucosinolates, which are characteristic secondary metabolites of the Brassicaceae that are known to act potentially as organic defense compounds. Growth of the test plants on metal‐amended soil led to a significant increase in leaf Cd and Zn concentrations when compared to control plants on unamended soil. After two initial months of growth under standardized greenhouse conditions, plants grown on different soils did not differ in size or biomass. In contrast, by the end of the 3‐month field exposure, test plants were larger than control plants. During field exposure, control plants were visited by more herbivores, suggesting that plants growing on metal‐amended soil were well defended against herbivores. Total glucosinolate concentrations were significantly higher in test compared to control plants only after the initial growth period under standardized conditions, but not by the end of the field exposure, pointing to joint effects of defenses particularly in young plants. Our results demonstrate that metal hyperaccumulation affords an effective elemental defense and enables increased growth under field conditions.
Metabolomics in plant–herbivore interactions: challenges and applications
Authors: Maag Daniel , Erb Matthias , Glauser Gaétan
Published: July 2015

Metabolomics as the study of the entire set of metabolites of a given organism is an important frontier in life sciences. As a tool that captures the ‘front end’ of cellular machineries, metabolomics is particularly suited to investigate biotic interactions, including for instance the interplay between plants and insects. In this review, we discuss the opportunities and challenges of metabolomics to study plant–herbivore interactions. We first present a brief overview of the typical analytical workflows used in metabolomics and their associated issues, in particular those related to metabolome coverage and compound identification. Second, recent advances in the field of plant–herbivore relationships that are promoted by non‐targeted approaches are reviewed, with examples ranging from classical herbivore resistance patterns to plant‐mediated interactions across different spatial scales and volatile‐mediated tritrophic interactions. Through general considerations and the discussion of a few selected case studies, our review highlights the potential and challenges of metabolomics as a research approach to understand biological interfaces.
Herbivory affects male and female reproductive success differently in dioecious Silene latifolia
Authors: Litto Maria , Scopece Giovanni , Fineschi Silvia , Schiestl Florian P. , Cozzolino Salvatore
Published: July 2015

In dioecious plants, reproductive efforts of male and female plants can be differentially affected by herbivory due to sex‐specific allocation and re‐modulation of resources. Here, we investigate the effects of foliar herbivory by the polyphagous species Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae) on male and female reproductive traits of Silene latifolia (Poir.) (Caryophyllaceae). We set up experimental populations of male and female control and Spodoptera‐infested plants and estimated flower morphology and phenology, and plant reproductive success. Herbivory did not affect floral traits involved in visual signalling to pollinators (flower size). Female reproductive success did not differ between Spodoptera‐infested and control plants in terms of seed set and seed germination. On the other hand, Spodoptera‐infested male plants produced fewer flowers than male control plants and maintained fewer flowers during flowering peaks. By experimental reduction in male flower number, we showed that male flower number is directly correlated with male reproductive success (pollen export to female flowers). This strongly suggests that male reproductive success is reduced after herbivory, whereas female reproductive success remains unaffected. The fact that females are more tolerant against herbivory is in accordance with sexual selection theory, which predicts that females, in contrast to males, are not selected for maximum investment in reproductive traits such as floral signalling, and should thus be more flexible in the allocation of resources.
The specific adsorption of organic and inorganic phosphates by variable‐charge oxides
Authors: Barrow N. J. , Feng X. H. , Yan Y. P.
Published: July 2015

We measured the reaction of inorganic phosphate and of four organic phosphates with three aluminium hydroxides or oxides. We compared the fit of the Langmuir equation with that of an equation designed to allow for the feedback effect of adsorption on the electric potential. We also fitted a four‐plane model to describe the effects of pH on adsorption and ζ potential. For inorganic phosphate, the Langmuir equation described adsorption curves poorly, indicating that there was a large feedback effect of adsorption on the electric potential of the adsorption plane. For the organic phosphates, the deviations from the Langmuir equation were not as marked, indicating that there was little feedback effect. Nevertheless, there was a large effect on the ζ potential of the phosphated aluminium (hydr)oxides. We suggest that when a large organic phosphate molecule is adsorbed, the charge conveyed to the surface is repelled electrostatically to the outside of the new surface. There is therefore a large effect on the ζ potential and a small effect on the potential of the adsorption plane. This suggestion was supported by the fit of the four‐plane model, for which, with increasing molecular weight, the mean position of the charge conveyed to the surface by adsorption was moved further from the plane carrying the potential determining ions (H+ and OH−).