bluuebunny/crossref_metadata_2025 huggingface dataset:
Recommendations for the Design and Analysis of Treatment Trials for Alcohol Use Disorders
Authors: Witkiewitz Katie , Finney John W. , Harris Alex H.S. , Kivlahan Daniel R. , Kranzler Henry R.
Published: August 2015

Background

Over the past 60 years, the view that “alcoholism” is a disease for which the only acceptable goal of treatment is abstinence has given way to the recognition that alcohol use disorders (AUDs) occur on a continuum of severity, for which a variety of treatment options are appropriate. However, because the available treatments forAUDs are not effective for everyone, more research is needed to develop novel and more efficacious treatments to address the range ofAUDseverity in diverse populations. Here we offer recommendations for the design and analysis of alcohol treatment trials, with a specific focus on the careful conduct of randomized clinical trials of medications and nonpharmacological interventions forAUDs.

Methods

This paper provides a narrative review of the quality of published clinical trials and recommendations for the optimal design and analysis of treatment trials forAUDs.

Results

Despite considerable improvements in the design of alcohol clinical trials over the past 2 decades, many studies ofAUDtreatments have used faulty design features and statistical methods that are known to produce biased estimates of treatment efficacy.

Conclusions

The published statistical and methodological literatures provide clear guidance on methods to improve clinical trial design and analysis. Consistent use of state‐of‐the‐art design features and analytic approaches will enhance the internal and external validity of treatment trials forAUDs across the spectrum of severity. The ultimate result of this attention to methodological rigor is that better treatment options will be identified for patients with anAUD.
Neural Firing in the Prefrontal Cortex During Alcohol Intake in Alcohol‐Preferring “P” Versus Wistar Rats
Authors: Linsenbardt David N. , Lapish Christopher C.
Published: August 2015

Background

Neural activity within the prefrontal cortex (PFC) is altered by alcohol and alcohol‐associated stimuli and is mediated by genetic susceptibility to alcoholism. However, very little is known about how genetic risk of excessive drinking might mediate neural firing in the PFC during alcohol consumption.

Methods

To determine how genetic risk influences alcohol seeking, intake, and neural activity, a Pavlovian alcohol consumption task was used—the 2‐Way Cued Access Protocol (2CAP). Alcohol‐preferring “P” rats and relatives of their (heterogeneous) founding Wistar population were used for these studies. After acquisition of 2CAP, extinction of responding for alcohol was evaluated by substituting water for alcohol. Following these experiments, in vivo electrophysiological recordings were obtained during 2CAP from the PFC in a separate cohort of Wistar and P rats implanted with moveable tetrode microdrives.

Results

P and Wistar rats increased daily alcohol seeking and intake with P rats consuming roughly twice as much alcohol as Wistar. Both rat populations decreased seeking behavior during extinction. However, P rats displayed persistent increases in seeking after controlling for intake versus Wistar. Higher firing rates (FRs) were observed in P rats prior to 2CAP and throughout alcohol and water consumption compared with Wistars that were matched for alcohol‐drinking history. Differences in FR were driven, in part, by a larger percentage of neurons in P rats versus Wistars that increased FR compared with those that decreased, or did not change.

Conclusions

These data provide additional evidence of increased alcohol consumption and persistent alcohol seeking in P versus Wistar rats. Differences in PFC neural firing observed in P rats prior to drinking could be heritable and/or related to an enhanced response to alcohol‐associated contextual cues. FR differences observed during alcohol drinking might be related to an augmented sensitivity of PFC neurons to orally consumed alcohol.
Time‐Dependent Effects of Ethanol on BK Channel Expression and Trafficking in Hippocampal Neurons
Authors: Palacio Stephanie , Velázquez‐Marrero Cristina , Marrero Héctor G. , Seale Garrett E. , Yudowski Guillermo A. , Treistman Steven N.
Published: August 2015

Background

The large conductance Ca2+‐ and voltage‐activated K+ channel (BK) is an important player in molecular and behavioral alcohol tolerance. Trafficking and surface expression of ion channels contribute to the development of addictive behaviors. We have previously reported that internalization of the BK channel is a component of molecular tolerance to ethanol (EtOH).

Methods

Using primary cultures of hippocampal neurons, we combine total internal reflection fluorescence microscopy, electrophysiology, and biochemical techniques to explore how exposure to EtOH affects the expression and subcellular localization of endogenous BK channels over time.

Results

Exposure to EtOH changed the expression of endogenous BK channels in a time‐dependent manner at the perimembrane area (plasma membrane and/or the area adjacent to it), while total protein levels of BK remain unchanged. These results suggest a redistribution of the channel within the neurons rather than changes in synthesis or degradation rates. Our results showed a temporally nonlinear effect of EtOH on perimembrane expression of BK. First, there was an increase in BK perimembrane expression after 10 minutes of EtOH exposure that remained evident after 3 hours, although not correlated to increases in functional channel expression. In contrast, after 6 hours of EtOH exposure, we observed a significant decrease in both BK perimembrane expression and functional channel expression. Furthermore, after 24 hours of EtOH exposure, perimembrane levels of BK had returned to baseline.

Conclusions

We report a complex time‐dependent pattern in the effect of EtOH on BK channel trafficking, including successive increases and decreases in perimembrane expression and a reduction in active BK channels after 3 and 6 hours of EtOH exposure. Possible mechanisms underlying this multiphasic trafficking are discussed. As molecular tolerance necessarily underlies behavioral tolerance, the time‐dependent alterations we see at the level of the channel may be relevant to the influence of drinking patterns on the development of behavioral tolerance.
CaMKIIα–GluA1 Activity Underlies Vulnerability to Adolescent Binge Alcohol Drinking
Authors: Agoglia Abigail E. , Holstein Sarah E. , Reid Grant , Hodge Clyde W.
Published: August 2015

Background

Binge drinking during adolescence is associated with increased risk for developing alcohol use disorders; however, the neural mechanisms underlying this liability are unclear. In this study, we sought to determine whether binge drinking alters expression or phosphorylation of 2 molecular mechanisms of neuroplasticity, calcium/calmodulin‐dependent kinase II alpha (CaMKIIα) and the GluA1 subunit of AMPA receptors (AMPARs) in addiction‐associated brain regions. We also asked whether activation of CaMKIIα‐dependent AMPAR activity escalates binge‐like drinking.

Methods

To address these questions, CaMKIIαT286 and GluA1S831 protein phosphorylation and expression were assessed in the amygdala and striatum of adolescent and adult male C57BL/6J mice immediately after voluntary binge‐like alcohol drinking (blood alcohol >80 mg/dl). In separate mice, effects of the CaMKIIα‐dependent GluA1S831 phosphorylation (pGluA1S831)‐enhancing drug tianeptine were tested on binge‐like alcohol consumption in both age groups.

Results

Binge‐like drinking decreased CaMKIIαT286 phosphorylation (pCaMKIIαT286) selectively in adolescent amygdala with no effect in adults. Alcohol also produced a trend for reduced pGluA1S831 expression in adolescent amygdala but differentially increased pGluA1S831 in adult amygdala. No effects were observed in the nucleus accumbens or dorsal striatum. Tianeptine increased binge‐like alcohol consumption in adolescents but decreased alcohol consumption in adults. Sucrose consumption was similarly decreased by tianeptine pretreatment in both ages.

Conclusions

These data show that the adolescent and adult amygdalae are differentially sensitive to effects of binge‐like alcohol drinking on plasticity‐linked glutamate signaling molecules. Tianeptine‐induced increases in binge‐like drinking only in adolescents suggest that differential CaMKIIα‐dependent AMPAR activation may underlie age‐related escalation of binge drinking.
Executive Functions and Motivation as Moderators of the Relationship Between Automatic Associations and Alcohol Use in Problem Drinkers Seeking Online Help
Authors: van Deursen Denise S. , Salemink Elske , Boendermaker Wouter J. , Pronk Thomas , Hofmann Wilhelm , Wiers Reinout W.
Published: August 2015

Background

Dual process models posit that problem drinking is maintained by an imbalance between relatively strong automatic processes and weak controlled processes, a combination of executive functions and motivation. Few studies have examined how the interplay between automatic processes and executive functions is affected by motivation to change. This study examined this relationship in problem drinkers seeking online help to change their alcohol use. It was expected that executive functions (i.e., working memory, response inhibition) would moderate the relationship between automatic (valence and approach) associations and alcohol use and that this effect would be stronger in individuals with strong motivation to change.

Methods

A sample of 302 problem drinkers (mean age: 51.7 years) participated in this study as part of the baseline assessment before an Internet intervention. Participants completed an online version of the brief Implicit Association Test (valence and approach associations), the self‐ordered pointing task (working memory), the Stroop task (response inhibition), the Readiness to Change Questionnaire (motivation to change), and the Timeline Follow‐Back Questionnaire (alcohol use). Hierarchical moderated regression analysis was used to test the 4 hypothesized 3‐way interactions.

Results

As expected, the interaction between valence associations and working memory only predicted alcohol use among individuals with strong motivation. This pattern was neither found for response inhibition nor for approach associations.

Conclusions

Results provide partial support for the moderating role of motivation in the interplay between automatic processes and executive functions. Future studies should investigate this relationship in participants with the full range of motivation and alcohol use.
Voter Buying: Shaping the Electorate through Clientelism
Authors: Hidalgo F. Daniel , Nichter Simeon
Published: August 2015

Studies of clientelism typically assume that political machines distribute rewards to persuade or mobilize the existing electorate. We argue that rewards not only influence actions of the electorate, but can also shape its composition. Across the world, machines employ “voter buying” to import outsiders into their districts. Voter buying demonstrates how clientelism can underpin electoral fraud, and it offers an explanation of why machines deliver rewards when they cannot monitor vote choices. Our analyses suggest that voter buying dramatically influences municipal elections in Brazil. A regression discontinuity design suggests that voter audits—which undermined voter buying—decreased the electorate by 12 percentage points and reduced the likelihood of mayoral reelection by 18 percentage points. Consistent with voter buying, these effects are significantly greater in municipalities with large voter inflows, and where neighboring municipalities had large voter outflows. Findings are robust to an alternative research design using a different data set.
Evaluation of Tp‐E Interval and Tp‐E/QT Ratio in Patients with Aortic Stenosis
Authors: Yayla Çağrı , Bilgin Murat , Akboğa Mehmet Kadri , Gayretli Yayla Kadriye , Canpolat Uğur , Dinç Asarcikli Lale , Doğan Mehmet , Turak Osman , Çay Serkan , Özeke Özcan , Akyel Ahmet , Yeter Ekrem , Aydoğdu Sinan
Published: August 2015

Background

The risk of syncope and sudden cardiac death due to ventricular arrhythmias increased in patients with aortic stenosis (AS). Recently, it was shown that Tp‐e interval, Tp‐e/QT, and Tp‐e/QTc ratio can be novel indicators for prediction of ventricular arrhythmias and mortality. We aimed to investigate the association between AS and ventricular repolarization using Tp‐e interval and Tp‐e/QT ratio.

Methods

Totally, 105 patients with AS and 60 control subjects were enrolled to this study. The severity of AS was defined by transthoracic echocardiographic examination. Tp‐e interval, Tp‐e/QT, and Tp‐e/QTc ratios were measured from the 12‐lead electrocardiogram.

Results

Tp‐e interval, Tp‐e/QT, and Tp‐e/QTc ratios were significantly increased in parallel to the severity of AS (P < 0.001, P = 0.001, and P = 0.001, respectively). Also, it was shown that Tp‐e/QTc ratio had significant positive correlation with mean aortic gradient (r = 0.192, P = 0.049). In multivariate logistic regression analysis, Tp‐e/QTc ratio and left ventricular mass were found to be independent predictors of severe AS (P = 0.03 and P = 0.04, respectively).

Conclusions

Our study showed that Tp‐e interval, Tp‐e/QT, and Tp‐e/QTc ratios were increased in patients with severe AS. Tp‐e/QTc ratio and left ventricular mass were found as independent predictors of severe AS.
Systematic review of the impact of sacral neuromodulation on clinical symptoms and gastrointestinal physiology
Authors: Mirbagheri Naseem , Sivakumaran Yogeesan , Nassar Natasha , Gladman Marc A.
Published: August 2015

Background

Sacral neuromodulation (SNM) has emerged as a treatment option for faecal incontinence (FI). However, its objective effect on symptoms and anorectal function is inconsistently described. This study aimed to systematically review the impact of SNM on clinical symptoms and gastrointestinal physiology in patients with FI, including factors that may predict treatment outcome.

Methods

An electronic search of MEDLINE (1946–2014)/EMBASE database was performed in accordance with PRISMA guidelines. Articles that reported the relevant outcome measures following SNM were included. Clinical outcomes evaluated included: frequency of FI episodes, FI severity score and success rates. Its impact on anorectal and gastrointestinal physiology was also evaluated.

Results

Of 554 citations identified, data were extracted from 81 eligible studies. Meta‐analysis of the data was precluded due to lack of a comparison group in most studies. After permanent SNM, ‘perfect’ continence was noted in 13–88% of patients. Most studies reported a reduction in weekly FI episodes (median difference of the mean −7.0 (range: −24.8 to −2.7)) and Wexner scores (median difference of the mean −9 (−14.9 to −6)). A trend towards improved resting and squeeze anal pressures and a reduction in rectal sensory volumes were noted. Studies failed to identify any consistent impact on other physiological parameters or clinicophysiological factors associated with success.

Conclusion

SNM improves clinical symptoms and reduces number of incontinence episodes and severity scores in patients with FI, in part by improving anorectal physiological function. However, intervention studies with standardized outcome measures and physiological techniques are required to robustly assess the physiological impact of SNM.
In the Nature of the Non‐City: Expanded Infrastructural Networks and the Political Ecology of Planetary Urbanisation
Authors: Arboleda Martín
Published: August 2015

This paper proposes extending Urban Political Ecology's (UPE) ideas about the urbanisation of nature in order to include the geographical imprints of expanding, global metabolic flows of matter, energy and capital. It does so through the analysis of Huasco, a small agricultural village in northern Chile that has been overburdened with massive energy undertakings aimed at powering the operations of mines that supply raw materials to international markets. Like the sewage and technological networks that feed the life of cities, the paper argues that Huasco—as a metabolic vehicle of planetary urbanisation—has also been hidden from view, and thus the fetishisation of urban infrastructural networks initially theorised by UPE, has been ratcheted‐up to the global level by the mediating powers of neoliberalising capitalism. Just as the socio‐material arrangements that facilitate the smooth functioning of the modern city and household are riddled with glitches and exclusions, the paper suggests that globally up‐scaled infrastructures reveal even larger contradictions that put into jeopardy the very premises upon which the ongoing commodification of nature is grounded.
Inference from PseudoLikelihoods with Plug‐In Estimates
Authors: Pace Luigi , Salvan Alessandra , Sartori Nicola
Published: August 2015

Effective implementation of likelihood inference in models for high‐dimensional data often requires a simplified treatment of nuisance parameters, with these having to be replaced by handy estimates. In addition, the likelihood function may have been simplified by means of a partial specification of the model, as is the case when composite likelihood is used. In such circumstances tests and confidence regions for the parameter of interest may be constructed using Wald type and score type statistics, defined so as to account for nuisance parameter estimation or partial specification of the likelihood. In this paper a general analytical expression for the required asymptotic covariance matrices is derived, and suggestions for obtaining Monte Carlo approximations are presented. The same matrices are involved in a rescaling adjustment of the log likelihood ratio type statistic that we propose. This adjustment restores the usual chi‐squared asymptotic distribution, which is generally invalid after the simplifications considered. The practical implication is that, for a wide variety of likelihoods and nuisance parameter estimates, confidence regions for the parameters of interest are readily computable from the rescaled log likelihood ratio type statistic as well as from the Wald type and score type statistics. Two examples, a measurement error model with full likelihood and a spatial correlation model with pairwise likelihood, illustrate and compare the procedures. Wald type and score type statistics may give rise to confidence regions with unsatisfactory shape in small and moderate samples. In addition to having satisfactory shape, regions based on the rescaled log likelihood ratio type statistic show empirical coverage in reasonable agreement with nominal confidence levels.
Regularised Manova for High‐Dimensional Data
Authors: Ullah Insha , Jones Beatrix
Published: August 2015

The traditional and readily available multivariate analysis of variance (MANOVA) tests such as Wilks' Lambda and the Pillai–Bartlett trace start to suffer from low power as the number of variables approaches the sample size. Moreover, when the number of variables exceeds the number of available observations, these statistics are not available for use. Ridge regularisation of the covariance matrix has been proposed to allow the use of MANOVA in high‐dimensional situations and to increase its power when the sample size approaches the number of variables. In this paper two forms of ridge regression are compared to each other and to a novel approach based on lasso regularisation, as well as to more traditional approaches based on principal components and the Moore‐Penrose generalised inverse. The performance of the different methods is explored via an extensive simulation study. All the regularised methods perform well; the best method varies across the different scenarios, with margins of victory being relatively modest. We examine a data set of soil compaction profiles at various positions relative to a ridgetop, and illustrate how our results can be used to inform the selection of a regularisation method.
Historic cohort study on mode of delivery of a macrosomic baby: the women's point of view
Authors: Vercellini Paolo , Fumagalli Monica , Consonni Dario , de Braud Lucrezia , Barbara Giussy , Iurlaro Enrico , Mosca Fabio , Fedele Luigi
Published: August 2015

Introduction

A historic cohort study was conducted to evaluate satisfaction with childbirth of a macrosomic baby according to mode of delivery.

Material and methods

All 559 nulliparous women who delivered a neonate weighing >4000 g between 2008 and 2012 were included. The degree of women's satisfaction with childbirth after elective cesarean, vaginal delivery or cesarean during labor was assessed using a five‐level scale. Immediate neonatal and maternal outcomes were retrieved from clinical records. Long‐term maternal outcomes were evaluated using four questionnaires on urinary incontinence, anal incontinence, and sexual functioning.

Results

Ninety‐nine women underwent elective cesarean, whereas 460 attempted a vaginal delivery. In the latter group, 276 women delivered vaginally, whereas 184 underwent a cesarean during labor. Long‐term outcomes were assessed in 273 women (49%; elective cesarean, n = 55; vaginal delivery, n = 135; cesarean in labor, n = 83) after a mean 3‐year follow up. The proportion of long‐term stress or mixed urinary incontinence was, respectively, 8%, 34%, and 12%, whereas that of anal incontinence was 7%, 19%, and 6%. Sexual functioning was similar in the three groups. No major neonatal complications were observed. When pooling the vaginal delivery and the cesarean in labor groups, the likelihood of being satisfied with childbirth was 63% in the “attempted vaginal delivery” group and 85% in the elective cesarean group (adjusted risk ratio, 0.72; 95% CI 0.61–0.84).

Conclusions

About one‐third of women attempting a vaginal delivery of a macrosomic baby, would choose an elective cesarean if they could turn back time.
Impact of obstetric factors on outcome of extremely preterm births in Sweden: prospective population‐based observational study (EXPRESS)
Authors: Källén Karin , Serenius Fredrik , Westgren Magnus , Maršál Karel ,   the EXPRESS Group
Published: August 2015

Introduction

A population‐based observational study investigated the contribution of obstetric factors to the survival and postnatal development of extremely preterm infants.

Material and methods

Mortality up to 1 year and neurodevelopment at 2.5 years (Bayley‐III test, cerebral palsy, vision, hearing) were evaluated in infants born before 27 weeks of gestation in Sweden 2004–2007 (n = 1011), using logistic regression analyses of risk factors.

Results

Of 844 fetuses alive at admission, 8.4% died in utero before labor, 7.8% died intrapartum. Of 707 live‐born infants, 15% died within 24 h, 70% survived ≥365 days, 64% were assessed at 2.5 years. The risk of death within 24 h after birth decreased with gestational age [odds ratio (OR) 0.3; 95% CI 0.2–0.4], antenatal corticosteroids (OR 0.3; 95% CI 0.1–0.6), and cesarean section (OR 0.4; 95% CI 0.2–0.9); it increased with multiple birth (OR 3.0; 95% CI 1.5–6.0), vaginal breech delivery (OR 2.3; 95% CI 1.0–5.1), 5‐min Apgar score <4 (OR 50.4; 95% CI 28.2–90.2), and birth at a level II hospital (OR 2.6; 95% CI 1.2–5.3). The risk of death between 1 and 365 days remained significantly decreased for gestational age and corticosteroids. The risk of mental developmental delay at 2.5 years decreased with gestational age, birthweight and fetal growth; it increased with vaginal breech delivery (OR 2.0; 95% CI 1.2–7.4), male gender, low Apgar score and high Clinical Risk Index for Babies score.

Conclusion

Several obstetric factors, including abdominal delivery, influenced the risk of death within the first day of life, but not later. Antenatal corticosteroids and gestational age decreased the mortality up to 1 year. Mental developmental delay was related to vaginal breech delivery.
Evaluation of postoperative pain at the stoma site in patients who underwent a single‐port Hartmann's procedure
Authors: Tei Mitsuyoshi , Wakasugi Masaki , Akamatsu Hiroki
Published: August 2015

Introduction

The aims of this retrospective study were to evaluate postoperative pain at the stoma site in patients who underwent a single‐port Hartmann's procedure (SPH) and to compare the SPH to the multiport Hartmann's procedure (MPH) in terms of postoperative pain.

Methods

We studied 17 consecutive patients who underwent SPH or MPH for left colon cancer. Postoperative pain was evaluated from postoperative day 1 to 7 with the Numeric Rating Scale.

Results

The postoperative pain score at the stoma site was highest on postoperative day 2 (Numeric Rating Scale score = 3.6). The duration of narcotics use was significantly shorter in the SPH group than in the MPH group (2.1 vs 3.3 days; P = 0.012). The rescue analgesia was administered fewer times in the SPH group than in the MPH group (1.3 vs 4.6; P = 0.012), and the duration of rescue analgesia use was shorter (1.1 vs 3.7 days; P = 0.013). The worst Numeric Rating Scale score in the SPH group was significantly lower than that in the MPH group on postoperative day 3 (1.9 vs 4.1; P = 0.031).

Conclusions

Postoperative pain at the stoma site was highest on postoperative day 2. The SPH was associated with less postoperative pain than the MPH.
Endoscopic interlaminar approach for intracanal L5‐S1 disc herniation: Classification of disc prolapse in relation to learning curve and surgical outcome
Authors: Passacantilli Emiliano , Lenzi Jacopo , Caporlingua Federico , Pescatori Lorenzo , Lapadula Gennaro , Nardone Antonio , Santoro Antonio
Published: August 2015

Introduction

The full endoscopic interlaminar approach (FEILA) is a minimally invasive procedure to treat intracanal lumbar disc herniation not approachable by endoscopic transforaminal access. Disc prolapses have been classified into three categories according to their position and passing nerve root displacement: (i) type A, in which the nerve root is displaced medially; (ii) type B, in which the nerve root is displaced laterally; and (iii) type C, in which the nerve root is ventrally displaced. We focused on the FEILA technique because it was likely to involve few complications and that provided the advantages of the endoscopic approach.

Methods

We prospectively evaluated 100 consecutive cases of L5‐S1 disc herniations operated on with FEILA, including 85 type A cases, 13 type B, and 2 type C. Patients were evaluated at discharge, 3 months, 6 months and 2 years.

Results

The operating time varied from 15 to 40 min. The use of drills and burrs was necessary to treat type B disc herniations; thus, it was preferable that these cases were operated on later in the learning curve. After surgery, 90% of neurological deficits improved. The Oswestry Disability Index and visual analog scale leg at last follow‐up were 15 and 9, respectively. There were no major complications. There were five cases of recurrence; four of which were treated with same technique and with good results.

Conclusion

FEILA is a safe procedure for the removal of intracanal L5‐S1 disc herniations. The late follow‐up confirms the stability of the results. We suggest treating type A prolapse at the beginning of the learning curve and type B herniations after sufficient experience in the use of the burrs has been achieved.
Surgery for synchronous colorectal cancers with double colonic anastomoses: A comparison of laparoscopic and open approaches
Authors: Takatsu Yukiko , Akiyoshi Takashi , Nagata Jun , Nagasaki Toshiya , Konishi Tsuyoshi , Fujimoto Yoshiya , Nagayama Satoshi , Fukunaga Yosuke , Ueno Masashi
Published: August 2015

Introduction

The aim of this study was to evaluate the safety of laparoscopic double colon resection and synchronous anastomosis for synchronous colorectal cancer.

Methods

We reviewed 42 consecutive patients who underwent double colon resection and synchronous anastomosis for synchronous colorectal cancer between 2000 and 2014. Clinical characteristics and short‐term outcomes were compared between laparoscopic (n = 27) and open (n = 15) groups.

Results

There was no conversion to open surgery in the laparoscopic group. Operating time in the laparoscopic group was significantly longer than in the open group (373 vs 292 min), but estimated blood loss was significantly lower (40 vs 179 mL). Time to first flatus (1 vs 3 days) and length of hospital stay (12 vs 17 days) were significantly shorter in the laparoscopic group. The rate of postoperative complications was similar in both groups (19% vs 27%). The anastomotic leakage rate was 3.7% in the laparoscopic group and 20.0% in the open group.

Conclusion

Laparoscopic surgery with double colon resection and synchronous anastomosis for synchronous colorectal cancers is safe and has greater short‐term benefits than open surgery. It should be considered as a treatment option under optimal conditions.
Satellite cells isolated from skeletal muscle will proliferate faster in WENS yellow feather chicks
Authors: Gao Chun‐Qi , Zhang Hao‐Jie , Yan Hui‐Chao , Yuan Li , Dahanayaka Sudath , Li Hai‐Chang , Wang Xiu‐Qi
Published: August 2015

This study was conducted to evaluate the differential proliferation ability of satellite cells (SCs) derived from pectoral muscles (PM) with different fiber characteristics and further to explore the underlying molecular mechanism. WENS Yellow Feather Chicks (WYFC) were chosen as the animal model, with White Plymouth Rock Chicks (WPRC) as a comparison. The results showed that WPRC had higher body and pectoral muscle weight than WYFC at 4 days old (P < 0.05). However, WYFC showed greater fiber numbers/mm2 but smaller fiber cross‐sectional area compared with WPRC in PM (P < 0.05). SCs derived from PM of WYFC had a faster proliferation rate but smaller cell size compared with that from PM of WPRC (P < 0.05). The percentage of cell population in G2/M phase and the messenger RNA abundance of TSC1 (P = 0.08), Rheb (P = 0.07) and target of rapamycin (TOR, P = 0.06) in WYFC were higher than that in WPRC. In conclusion, our results demonstrated that SCs isolated from PM of WYFC had faster proliferation rate but smaller cell size than that in WPRC. The higher SC proliferation in WYFC may be due to higher gene expression of TOR signaling pathway than in WPRC, and the larger cell size of WPRC may be due to higher insulin‐like growth factor‐1 expression than in WYFC.
Mycophenolate mofetil therapy for severe immune thrombocytopenia
Authors: Taylor Alice , Neave Lucy , Solanki Shalini , Westwood John Paul , Terrinonive Ilaria , McGuckin Siobhan , Kothari Jaimal , Cooper Nichola , Stasi Roberto , Scully Marie
Published: August 2015

Severe immune thrombocytopenia purpura (ITP) presents a clinical challenge. Second‐line treatment options are variable without a precise protocol. We present 46 severe ITP patients treated with mycophenolate mofetil (MMF), retrospectively identified from three London teaching hospitals. Data was collected on patient demographics, co‐morbidities and previous treatment strategies. Our key interest was whether there was a sustained response in platelet count to MMF. Patients included 27 males and 19 females whose ages ranged from 19 to 93 years old (median 52·5 years). Twenty‐nine had primary ITP and 17 had secondary ITP, a third of whom had viral‐associated disease. The standard dose of MMF was 1 g/day. Twenty‐four patients (52%) responded with 15 (33%) achieving a complete response. No active viral‐associated ITP patients demonstrated a response to MMF, although numbers were small (n = 4). We were not able to demonstrate a difference between responders and non‐responders based on gender, age, previous therapies or time since diagnosis of ITP. Three of four previously splenectomized patients responded, two achieving complete response. We conclude that MMF is a useful steroid‐sparing immunosuppressant to be considered in the second‐line or later treatment of ITP.
Molecular dynamics and functional studies define a hot spot of crystal contacts essential for PcTx1 inhibition of acid‐sensing ion channel 1a
Authors: Saez Natalie J , Deplazes Evelyne , Cristofori‐Armstrong Ben , Chassagnon Irène R , Lin Xiaozhen , Mobli Mehdi , Mark Alan E , Rash Lachlan D , King Glenn F
Published: August 2015

Background and Purpose

The spider‐venom peptide PcTx1 is the most potent and selective inhibitor of acid‐sensing ion channel (ASIC) 1a. It has centrally acting analgesic activity and is neuroprotective in rodent models of ischaemic stroke. Understanding the molecular details of the PcTx1 : ASIC1a interaction should facilitate development of therapeutically useful ASIC1a modulators. Previously, we showed that several key pharmacophore residues of PcTx1 reside in a dynamic β‐hairpin loop; conclusions confirmed by recent crystal structures of the complex formed between PcTx1 and chicken ASIC1 (cASIC1). Numerous peptide : channel contacts were observed in these crystal structures, but it remains unclear which of these are functionally important.

Experimental Approach

We combined molecular dynamics (MD) simulations of the PcTx1 : cASIC1 complex with mutagenesis of PcTx1 and rat ASIC1a.

Key Results

Crystal structures of the PcTx1 : cASIC1 complex indicated that 15 PcTx1 residues form a total of 57 pairwise intermolecular contacts (<5 Å) with 32 channel residues. MD simulations, however, suggested that about half of these interactions do not persist in solution. Mutation to alanine of only eight of 15 PcTx1 contact residues substantially altered ASIC1a inhibition by PcTx1. Our data reveal that many of the peptide–channel interactions observed in the PcTx1 : cASIC1 crystal structures are not important for PcTx1 inhibition of rat ASIC1a.

Conclusions and Implications

We identified the atomic interactions that are critical for PcTx1 inhibition of ASIC1a. Our data highlight the value of combining structural information, MD and functional experiments to obtain detailed insight into the molecular basis of protein : protein interactions.
Different downstream signalling of CCK1 receptors regulates distinct functions of CCK in pancreatic beta cells
Authors: Ning Shang‐lei , Zheng Wen‐shuai , Su Jing , Liang Nan , Li Hui , Zhang Dao‐lai , Liu Chun‐hua , Dong Jun‐hong , Zhang Zheng‐kui , Cui Min , Hu Qiao‐Xia , Chen Chao‐chao , Liu Chang‐hong , Wang Chuan , Pang Qi , Chen Yu‐xin , Yu Xiao , Sun Jin‐peng
Published: August 2015

Background and Purpose

Cholecystokinin (CCK) is secreted by intestinal I cells and regulates important metabolic functions. In pancreatic islets, CCK controls beta cell functions primarily through CCK1 receptors, but the signalling pathways downstream of these receptors in pancreatic beta cells are not well defined.

Experimental Approach

Apoptosis in pancreatic beta cell apoptosis was evaluated using Hoechst‐33342 staining, TUNEL assays and Annexin‐V‐FITC/PI staining. Insulin secretion and second messenger production were monitored using ELISAs. Protein and phospho‐protein levels were determined by Western blotting. A glucose tolerance test was carried out to examine the functions of CCK‐8s in streptozotocin‐induced diabetic mice.

Key Results

The sulfated carboxy‐terminal octapeptide CCK26‐33 amide (CCK‐8s) activated CCK1 receptors and induced accumulation of both IP3 and cAMP. Whereas Gq‐PLC‐IP3 signalling was required for the CCK‐8s‐induced insulin secretion under low‐glucose conditions, Gs‐PKA/Epac signalling contributed more strongly to the CCK‐8s‐mediated insulin secretion in high‐glucose conditions. CCK‐8s also promoted formation of the CCK1 receptor/β‐arrestin‐1 complex in pancreatic beta cells. Using β‐arrestin‐1 knockout mice, we demonstrated that β‐arrestin‐1 is a key mediator of both CCK‐8s‐mediated insulin secretion and of its the protective effect against apoptosis in pancreatic beta cells. The anti‐apoptotic effects of β‐arrestin‐1 occurred through cytoplasmic late‐phase ERK activation, which activates the 90‐kDa ribosomal S6 kinase‐phospho–Bcl‐2‐family protein pathway.

Conclusions and Implications

Knowledge of different CCK1 receptor‐activated downstream signalling pathways in the regulation of distinct functions of pancreatic beta cells could be used to identify biased CCK1 receptor ligands for the development of new anti‐diabetic drugs.
Forest Fragmentation Drives the Loss of Insectivorous Birds and an Associated Increase in Herbivory
Authors: Peter Franziska , Berens Dana G. , Grieve Graham R. , Farwig Nina
Published: August 2015

Insectivorous birds are known to play a decisive role for the natural control of herbivorous insects. Thus, they enhance the growth, reproduction, and survival of plant individuals and in the long‐term benefit plant regeneration. However, particularly in the tropics, forest fragmentation has been suggested to cause a loss of insectivorous birds. Yet, it is unclear whether this hampers the trophic control of herbivorous insects with potential consequences for plants. Therefore, we investigated the effect of increasing forest fragmentation on tritrophic interactions between insectivorous birds, herbivorous insects, and plants in a subtropical forest landscape, South Africa. We monitored the community composition of birds and estimated insectivorous bird abundances along a gradient of forest fragmentation. In the same sites, we installed bird exclosures on a common plant species (Englerophytum natalense) to assess effects of the trophic control of insectivorous birds on herbivorous insects and leaf area loss (LAL). Forest fragmentation strongly shaped the functional composition of bird communities, particularly through a loss of forest‐dependent insectivorous birds. Moreover, LAL was higher within bird exclosures than on control branches and increased with increasing forest fragmentation on the control branches. Altogether, forest fragmentation seems to hamper the trophic control of herbivorous insects by insectivorous birds through changes in the community composition. This, in turn, may interfere with tritrophic interactions and ecological processes. Thus, conservation efforts aiming at enhancing the natural control of herbivorous insects should focus on the maintenance of continuous indigenous forests that are well‐connected to smaller forest fragments on the landscape scale.
Communicative interactions between visually impaired mothers and their sighted children: analysis of gaze, facial expressions, voice and physical contacts
Authors: Chiesa S. , Galati D. , Schmidt S.
Published: August 2015

Background

Social and emotional development of infants and young children is largely based on the communicative interaction with their mother, or principal caretaker (Trevarthen ). The main modalities implied in this early communication are voice, facial expressions and gaze (Stern ). This study aims at analysing early mother–child interactions in the case of visually impaired mothers who do not have access to their children's gaze and facial expressions.

Methods

Spontaneous play interactions between seven visually impaired mothers and their sighted children aged between 6 months and 3 years were filmed. These dyads were compared with a control group of sighted mothers and children analysing four modalities of communication and interaction regulation: gaze, physical contacts, verbal productions and facial expressions.

Results

The visually impaired mothers' facial expressions differed from the ones of sighted mothers mainly with respect to forehead movements, leading to an impoverishment of conveyed meaning. Regarding the other communicative modalities, results suggest that visually impaired mothers and their children use compensatory strategies to guaranty harmonic interaction despite the mother's impairment: whereas gaze results the main factor of interaction regulation in sighted dyads, physical contacts and verbal productions assume a prevalent role in dyads with visually impaired mothers. Moreover, visually impaired mother's children seem to be able to differentiate between their mother and sighted interaction partners, adapting differential modes of communication.

Conclusions

The results of this study show that, in spite of the obvious differences in the modes of communication, visual impairment does not prevent a harmonious interaction with the child.
Reciprocal Relations Between Student–Teacher Relationship and Children's Behavioral Problems: Moderation by Child‐Care Group Size
Authors: Skalická Věra , Belsky Jay , Stenseng Frode , Wichstrøm Lars
Published: August 2015

In this Norwegian study, bidirectional relations between children's behavior problems and child–teacher conflict and closeness were examined, and the possibility of moderation of these associations by child‐care group size was tested. Eight hundred and nineteen 4‐year‐old children were followed up in first grade. Results revealed reciprocal effects linking child–teacher conflict and behavior problems. Effects of child–teacher closeness on later behavior problems were moderated by group size: For children in small groups only (i.e., ≤ 15 children), greater closeness predicted reduced behavior problems in first grade. In consequence, stability of behavior problems was greater in larger than in smaller groups. Results are discussed in light of regulatory mechanisms and social learning theory, with possible implications for organization of child care.
A Survey of Geometric Analysis in Cultural Heritage
Authors: Pintus Ruggero , Pal Kazim , Yang Ying , Weyrich Tim , Gobbetti Enrico , Rushmeier Holly
Published: August 2015

We present a review of recent techniques for performing geometric analysis in cultural heritage (CH) applications. The survey is aimed at researchers in the areas of computer graphics, computer vision and CH computing, as well as to scholars and practitioners in the CH field. The problems considered include shape perception enhancement, restoration and preservation support, monitoring over time, object interpretation and collection analysis. All of these problems typically rely on an understanding of the structure of the shapes in question at both a local and global level. In this survey, we discuss the different problem forms and review the main solution methods, aided by classification criteria based on the geometric scale at which the analysis is performed and the cardinality of the relationships among object parts exploited during the analysis. We finalize the report by discussing open problems and future perspectives.
Adhesion Properties of Human Oral Epithelial‐Derived Cells to Zirconia
Authors: Okabe Eijiro , Ishihara Yuichi , Kikuchi Takeshi , Izawa Ario , Kobayashi Shuichiro , Goto Hisashi , Kamiya Yosuke , Sasaki Keisuke , Ban Seiji , Noguchi Toshihide , Kawai Tatsushi , Mitani Akio
Published: August 2015

Background

Few studies have examined epithelial attachment to zirconia and the proliferative ability of epithelial cells on zirconia surfaces.

Purpose

To evaluate the adhesion properties of zirconia materials for epithelial cell attachment and compare this with titanium and alumina.

Materials and Methods

Human oral epithelial cells were cultured on smooth‐surfaced specimens of commercially pure titanium (cpTi), ceria‐stabilized zirconia/alumina nano‐composite (P‐NANOZR), yttria‐stabilized zirconia (Cercon), and alumina oxide (inCoris AL). The cell morphology, the cell viability and mRNA of integrin β4, laminin γ2, catenin δ2, and E‐cadherin were evaluated by SEM, Cell‐Counting Kit‐8, and real‐time PCR, respectively.

Results

Morphology of cells attached to specimens was similar among all groups. The viable cell numbers on Cercon and inCoris AL after 24 hours culture were significantly higher than for cpTi. Integrin β4, laminin γ2, and catenin δ2 mRNA expression was not different among all groups. However, at 3 and 24 hours after incubation, E‐cadherin mRNA expression in the P‐NANOZR group was significantly higher than for cpTi.

Conclusion

Zirconia may support binding of epithelial cells through hemidesmosomes comparable with titanium. Furthermore, P‐NANOZR may impart resistance to exogenous stimuli through strong intercellular contacts with peri‐implant mucosal cells when used as an abutment and implant superstructure.
Effect of double conical abutment screw on implant preload
Authors: Arnetzl Gerwin Vincent , Payer Michael , Falkensammer Frank , Arnetzl Gerwin
Published: August 2015

Objective

This study compared the loosening torque of experimental double conical abutment screws to that of conventional conical abutment screws and flat‐head screws in implants with internal connections before and after mechanical loading.

Material and methods

Eighty implant–screw–abutment assemblies were divided into four groups: flat‐head screw (Xive S), conical screw (Straumann), conical screw (Nobel Biocare), and double conical screw (RTB). Abutments were tightened to a torque of 30 Ncm. After 10 min, they were retightened and loosening torque was measured. The same abutments were then retightened with new screws to a torque of 30 Ncm and, again, retightened after 10 min. They were then mechanically loaded for 3 000 000 cycles, and loosening torque was again measured. Data were collected, and an exploratory analysis was performed.

Results

Comparisons before mechanical cycling showed significant differences between groups. After mechanical cycling, only the comparisons of Straumann and Nobel Biocare showed no significant differences. Considering the same group before and after mechanical cycling, all comparisons showed significant differences.

Conclusion

The shape of the abutment screw head significantly influenced loosening torque: Double conical‐head screws showed significantly higher loosening torque values than conical‐head screws. Conical‐head screws showed higher loosening torque values than conventional flat‐head screws before and after loading.
Outpatient‐based injection laryngoplasty for the management of unilateral vocal fold paralysis – clinical outcomes from a UK centre
Authors: Mohammed H. , Masterson L. , Gendy S. , Nassif R.
Published: August 2015

Objective

To assess voice outcomes in patients undergoing vocal fold injection (VFI) augmentation laryngoplasty in a clinic‐based setting.

Methods

A prospective study of patients with unilateral vocal cord palsy undergoing Radiesse® vocal cord augmentation. We used the ten‐item voice handicap index (VHI‐10) as a postal survey before and after the intervention.

Results

A total of 43 patients were referred to our ENT clinic from June 2011 to October 2014 with unilateral vocal cord palsy. The majority were referred from the oncology department with mediastinal tumours. Fifteen patients died of malignant disease. Twenty‐one patients responded to our survey. VHI‐10 scores were analysed using one‐way analysis of variance (anova), and the results suggest a sustained improvement before and after the intervention (pre‐injection versus 3 months post‐injection P < 0.01; pre‐injection versus 6 months post‐injection P < 0.033).

Conclusion

This is the largest case series of patients who had a local anaesthetic vocal cord injection with calcium hydroxylapaptite using the trans‐thyrohyoid approach. Early data would suggest that the results are similar to injections performed under general anaesthesia when performed by an experienced laryngologist. VFI in a clinic‐based (awake) setting has the distinct advantage of providing instant feedback of vocal fold closure and voice outcome during the procedure, avoiding general anaesthesia with its inherent risks and cost and also the limitations of difficult exposure.
A surgical view on the treatment of Madelung's disease
Authors: Sharma N. , Hunter‐Smith D. J. , Rizzitelli A. , Rozen W. M.
Published: August 2015

Benign symmetrical lipomatosis (Madelung's disease) is a rare condition of unclear aetiology characterized by numerous, unencapsulated lipomatous deposits. The only effective treatment is by surgical intervention; however, there is no consensus in the optimal approach. We present the case of a patient who required staged, multi‐modality treatment to achieve disease quiescence. The case highlights the usefulness of magnetic resonance imaging as a tool for assessment as well as preoperative planning.