bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue transformation mold design and stereolithography fabrication
Authors: Zheng Yihao , Wang Yancheng , Chen Roland K. , Deshpande Sagar , Nelson Noah S. , Buchman Steven R. , Shih Albert J.
Published: February 2017

Purpose

To obtain a vascularized autologous bone graft by in-vivo tissue transformation, a biocompatible tissue transformation mold (TTM) is needed. An ideal TTM is of high geometric accuracy and X-ray radiolucent for monitoring the bone tissue formation. The purpose of this study is to present the TTM design and fabrication process, using 3D reconstruction, stereolithography (SLA) and silicone molding.

Design/methodology/approach

The rat mandible, the targeted bone graft, was scanned by micro-computed tomography (CT). From the micro-CT images, the 3D mandible model was identified and used as the cavity geometry to design the TTM. The TTM was fabricated by molding the biocompatible and radiolucent silicone in the SLA molds. This TTM was implanted in a rat for in vivo tests on its biocompatibility and X-ray radiolucency.

Findings

SLA can fabricate the TTM with a cavity shape that accurately replicates that of the rat mandible. The bone formation inside of the silicone TTM can be observed by X-ray. The TTM is feasible for in vivo tissue transformation for vascularized bone reconstruction.

Research limitations/implications

Research of the dimensional and geometrical accuracy of the TTM cavity is required in the future study of this process.

Practical implications

The TTM fabricated in this presented approach has been used for in-vivo tissue transformation. This technique can be implemented for bone reconstruction.

Originality/value

The precision fabrication of the TTMs for in-vivo tissue transformation into autogenous vascularized bone grafts with complex structures was achieved by using SLA, micro-CT and silicone molding.
Development of CNTs-filled photopolymer for projection stereolithography
Authors: Eng Hengky , Maleksaeedi Saeed , Yu Suzhu , Choong Yu Ying Clarrisa , Wiria Florencia Edith , Kheng Ruihua Eugene , Wei Jun , Su Pei-Chen , Tham Huijun Phoebe
Published: February 2017

Purpose

Polymeric parts produced by 3D stereolithography (SL) process have poorer mechanical properties as compared to their counterparts fabricated via conventional methods, such as injection or compression molding. Adding nanofillers in the photopolymer resin for SL could help improve mechanical properties. This study aims to achieve enhancement in mechanical properties of parts fabricated by SL, for functional applications, by using well-dispersed nanofillers in the photopolymers, together with suitable post-processing.

Design/methodology/approach

Carbon nanotubes (CNTs) have high strength and Young’s modulus, making them attractive nanofillers. However, dispersion of CNTs in photopolymer is a critical challenge, as they tend to agglomerate easily. Achieving good dispersion is crucial to improve the mechanical properties; thus, suitable dispersion mechanisms and processes are examined. Solvent exchange process was found to improve the dispersion of multiwalled carbon nanotubes in the photopolymer. The UV-absorbing nature of CNTs was also discovered to affect the curing properties. With suitable post processing, coupled with thermal curing, the mechanical properties of SL parts made from CNTs-filled resin improved significantly.

Findings

With the addition of 0.25 wt.% CNTs into the photopolymer, tensile stress and elongation of the 3D printed parts increased by 70 and 46 per cent, respectively. With the significant improvement, the achieved tensile strength is comparable to parts manufactured by conventional methods.

Practical implications

This allows functional parts to be manufactured using SL.

Originality/value

In this paper, an improved procedure to incorporate CNTs into the photopolymer was developed. Furthermore, because of strong UV-absorption nature of CNTs, curing properties of photopolymer and SL parts with and without CNT fillers were studied. Optimized curing parameters were determined and additional post-processing step for thermal curing was discovered as an essential step in order to further enhance the mechanical properties of SL composite parts.
A digital design methodology for surgical planning and fabrication of customized mandible implants
Authors: Abouel Nasr Emad , Al-Ahmari Abdurahman Mushabab , Moiduddin Khaja , Al Kindi Mohammed , Kamrani Ali K.
Published: February 2017

Purpose

The purpose of this paper is to demonstrate the route to digitize the customized mandible implants consisting of image acquisition, processing, implant design, fitting rehearsal and fabrication using fused deposition modeling and electron beam melting methodologies.

Design/methodology/approach

Recent advances in the field of rapid prototyping, reverse engineering, medical imaging and image processing have led to new heights in the medical applications of additive manufacturing (AM). AM has gained a lot of attention and interest during recent years because of its high potential in medical fields.

Findings

Produced mandible implants using casting, milling and machining are of standard sizes and shapes. As each person’s physique and anatomical bone structure are unique, these commercially produced standard implants are manually bent before surgery using trial and error methodology to custom fit the patient’s jaw. Any mismatch between the actual bone and the implant results in implant failure and psychological stress and pain to the patient.

Originality/value

The novelty in this paper is the construction of the customized mandibular implant from the computed tomography (CT) scan which includes surface reconstruction, implant design with validation and simulation of the mechanical behavior of the design implant using finite element analysis (FEA). There has been few research studies on the design and customization of the implants before surgery, but there had been hardly any study related to customized design implant and evaluating the biomechanical response on the newly designed implant using FEA. Though few studies are related to FEA on the reconstruction plates, but their paper lacks the implant design model and the reconstruction model. In this research study, an integrated framework is developed for the implant design, right from the CT scan of the patient including the softwares involved through out in the study and then performing the biomechanical study on the customized design implant to prove that the designed implant can withstand the biting and loading conditions. The proposed research methodology which includes the interactions between medical practitioners and the implant design engineers can be incorporated to any other reconstruction bone surgeries.
Investigation of additive manufacturing surface smoothing process
Authors: Cunico Marlon Wesley Machado , Cunico Miriam Machado , Cavalheiro Patrick Medeiros , de Carvalho Jonas
Published: February 2017

Purpose

The additive manufacturing technologies have been facing an extraordinary growth along the past years. This phenomenon might be correlated with rise of low-cost FDM technologies into the non-professional market segment. In contrast with that, among the main disadvantages found in this sort of equipment are the final object finishing and low mechanical strength. For that reason, the purpose of this paper is to present and characterise a surface treatment which is based on solvent vapour attack and that is also known as smoothing process. In addition, a concise overview about the theory beneath this process is presented besides an experimental study that evaluates the main effects on the mechanical properties of object.

Design/methodology/approach

To analyse the benefits of this process, the authors preliminarily investigated the working mechanism that supports such surface treatment. It allowed them to identify and select a proper solvent for each material. The authors have also established that the exposure time repetition numbers (passes) were the main variables, whereas temperature, solvent type, drying time, object direction and object shape were constants. The main object dimensions, surface roughness, absorbed solvent mass and mechanical strength were the main study responses.

Findings

As a result of this work, the peak-peak roughness was reduced in 71 per cent, indicating the potential benefit of this process. On the other hand, excessive solvent exposure implied on relevant dimensional distortions and internal disruptures. It was also possible to see that the vapourised solvent penetrate into the object surface and fused layers and filaments. As consequence, the mechanical strength was also improved.

Originality/value

Despite the growth that additive manufacturing market segment has seen along the past years, the finishing and mechanical strength of low-cost equipment still lack for improvements. For that reason, applications like solvent vapour attack or smoothing process new perspectives for this non-professional segment, whereas roughness and mechanical strength are improved after its treatment. As a consequence, it is possible to consider a final object to be obtained directly from low-cost FDM in combination with smoothing process.
Structure and mechanical behavior of Big Area Additive Manufacturing (BAAM) materials
Authors: Duty Chad E. , Kunc Vlastimil , Compton Brett , Post Brian , Erdman Donald , Smith Rachel , Lind Randall , Lloyd Peter , Love Lonnie
Published: February 2017

Purpose

This paper aims to investigate the deposited structure and mechanical performance of printed materials obtained during initial development of the Big Area Additive Manufacturing (BAAM) system at Oak Ridge National Laboratory. Issues unique to large-scale polymer deposition are identified and presented to reduce the learning curve for the development of similar systems.

Design/methodology/approach

Although the BAAM’s individual extruded bead is 10-20× larger (∼9 mm) than the typical small-scale systems, the overall characteristics of the deposited material are very similar. This study relates the structure of BAAM materials to the material composition, deposition parameters and resulting mechanical performance.

Findings

Materials investigated during initial trials are suitable for stiffness-limited applications. The strength of printed materials can be significantly reduced by voids and imperfect fusion between layers. Deposited material was found to have voids between adjacent beads and micro-porosity within a given bead. Failure generally occurs at interfaces between adjacent beads and successive layers, indicating imperfect contact area and polymer fusion.

Practical implications

The incorporation of second-phase reinforcement in printed materials can significantly improve stiffness but can result in notable anisotropy that needs to be accounted for in the design of BAAM-printed structures.

Originality/value

This initial evaluation of BAAM-deposited structures and mechanical performance will guide the current research effort for improving interlaminar strength and process control.
Life‐history strategy determines constraints on immune function
Authors: Parker Benjamin J. , Barribeau Seth M. , Laughton Alice M. , Griffin Lynn H. , Gerardo Nicole M.
Published: February 2017

Determining the factors governing investment in immunity is critical to understanding host–pathogen ecological and evolutionary dynamics. Studies often consider disease resistance in the context of life‐history theory, with the expectation that investment in immunity will be optimized in anticipation of disease risk. Immunity, however, is constrained by context‐dependent fitness costs. How the costs of immunity vary across life‐history strategies has yet to be considered.

Pea aphids are typically unwinged but produce winged offspring in response to high population densities and deteriorating conditions. This is an example of polyphenism, a strategy used by many organisms to adjust to environmental cues. The goal of this study was to examine the relationship between the fitness costs of immunity, pathogen resistance and the strength of an immune response across aphid morphs that differ in life‐history strategy but are genetically identical.

We measured fecundity of winged and unwinged aphids challenged with a heat‐inactivated fungal pathogen, and found that immune costs are limited to winged aphids. We hypothesized that these costs reflect stronger investment in immunity in anticipation of higher disease risk, and that winged aphids would be more resistant due to a stronger immune response. However, producing wings is energetically expensive. This guided an alternative hypothesis – that investing resources into wings could lead to a reduced capacity to resist infection.

We measured survival and pathogen load after live fungal infection, and we characterized the aphid immune response to fungi by measuring immune cell concentration and gene expression. We found that winged aphids are less resistant and mount a weaker immune response than unwinged aphids, demonstrating that winged aphids pay higher costs for a less effective immune response.

Our results show that polyphenism is an understudied factor influencing the expression of immune costs. More generally, our work shows that in addition to disease resistance, the costs of immunity vary between individuals with different life‐history strategies. We discuss the implications of these findings for understanding how organisms invest optimally in immunity in the light of context‐dependent constraints.
Development, histological observations and Grapevine leafroll‐associated virus‐3 localisation in in vitro grapevine micrografts
Authors: Hao X.‐Y. , Bi W.‐L. , Cui Z.‐H. , Pan C. , Xu Y. , Wang Q.‐C.
Published: February 2017

Development, histological process and Grapevine leafroll‐associated virus‐3 localisation were studied in micrografts of three scion/rootstock combinations: healthy/healthy, healthy/infected and infected/healthy. Earlier bud break and faster growth in scions of micrografts were obtained when the healthy shoot segments were used as scions, while earlier bud break in rootstocks and greater fresh weight of roots in micrografts were produced when the healthy shoot segments were used as rootstocks. All histological processes including callus initiation and formation in micrografting conjunctions, and initiation of new cambial cells followed by vascular bundle development connecting scions and rootstocks were similar in micrografts, regardless of the sanitary status of the scions and rootstocks used for micrografting. Virus infection in micrografting conjunctions and systematic infection in micrografts were much more efficient and faster in micrografting combination of the infected scions/healthy rootstocks than in the healthy scions/infected rootstocks. To the best of our knowledge, this is the first report addressing histological process of micrograft development and virus localisation in micrografts. In vitro culture system established in this study facilitates studies on the ‘pure’ impact of the viral infection on micrografting.
Oxytocin Reduces Ethanol Self‐Administration in Mice
Authors: King Courtney E. , Griffin William C. , Luderman Lauryn N. , Kates Malcolm M. , McGinty Jacqueline F. , Becker Howard C.
Published: February 2017

Background

Excessive ethanol (EtOH) consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces EtOH consumption.

Methods

Male C57BL/6J mice were given access to EtOH (20% v/v) using a model of binge‐like drinking (“drinking in the dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2‐bottle choice drinking in the home cage. In addition, EtOH (12% v/v) and sucrose (5% w/v) self‐administration on fixed‐ and progressive‐ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models.

Results

Oxytocin (0, 0.3, 1, 3, or 10 mg/kg) dose dependently reduced EtOH consumption (maximal 45% reduction) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist, and the pattern of contacts (licks) at the EtOH bottle suggested a reduction in motivation to drink EtOH. Oxytocin decreased 2‐bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for EtOH and sucrose in a dose‐related manner. However, oxytocin decreased responding and motivation (breakpoint values) for EtOH at doses that did not alter responding for sucrose.

Conclusions

These results indicate that oxytocin reduces EtOH consumption in different models of self‐administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for EtOH at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Nevertheless, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder.
Relationship between QT and JT peak interval variability in prepubertal children
Authors: Takeuchi Yuka , Omeki Yumi , Horio Kayo , Nishio Miki , Nagata Rina , Oikawa Shota , Mizutani Yuri , Nagatani Arisa , Funamoto Yuri , Uchida Hidetoshi , Fujino Masayuki , Eryu Yoshihiko , Boda Hiroko , Miyata Masafumi , Hata Tadayoshi
Published: February 2017

Background

The QT variability index (QTVI) is a noninvasive index of repolarization lability that has been applied to subjects with cardiovascular disease. QTVI provides a ratio of normalized QT variability to normalized heart rate variability, and therefore includes an assessment of autonomic nervous activity. However, measurement of QT time is particularly difficult in children, who exhibit physiologically high heart rates compared with adults. In this study, we developed a set of standard values of J‐point to Tpeak interval (JTp) for infants by age, and assessed the correlation of QTVI with the JTp variability index (JTpVI).

Methods

Subjects included 623 infants and children (0–7 years of age) without heart disease and 57 healthy university students. All subjects were divided into three groups by age. QTVI and JTpVI were calculated based on an electrocardiogram, and age‐specific standard values, a gender‐specific classification, and a standard growth curve were constructed.

Results

JTpVI markedly decreased in infancy and slowly decreased thereafter, reaching adult values by school age. There was also a strong correlation of JTpVI with QTVI (r = .856).

Conclusions

JTp can be used to evaluate the variability of the repolarization time in healthy infants, and may be useful for detection of early repolarization abnormalities.
The interrelation between hypothyroidism and glaucoma: a critical review and meta‐analyses
Authors: Thvilum Marianne , Brandt Frans , Brix Thomas Heiberg , Hegedüs Laszlo
Published: February 2017

Data on the association between hypothyroidism and glaucoma are conflicting. We sought to shed light on this by conducting a critical review and meta‐analyses. The meta‐analyses were conducted in adherence with the widely accepted MOOSE guidelines. Using the Medical Subject Heading (MeSH) terms: hypothyroidism, myxoedema and glaucoma or intraocular pressure, case–control studies, cohort studies and cross‐sectional studies were identified (PubMed) and reviewed. Using meta‐analysis, the relative risk (RR) of coexistence of glaucoma and hypothyroidism was calculated. Based on the literature search, thirteen studies fulfilled the inclusion criteria and could be categorized into two groups based on the exposure. The designs of the studies varied considerably, and there was heterogeneity related to lack of power, weak phenotype classifications and length of follow‐up. Eight studies had glaucoma (5757 patients) as exposure and hypothyroidism as outcome. Among these, we found a non‐significantly increased risk of hypothyroidism associated with glaucoma (RR 1.65; 95% confidence interval [CI]: 0.97–2.82). Based on five studies (168 006 patients) with hypothyroidism as exposure and glaucoma as outcome, we found the risk of glaucoma to be significantly increased (RR 1.33; 95% CI: 1.13–1.58). Based on these meta‐analyses, there seems to be an association between hypothyroidism and glaucoma, which does not seem to be the case between glaucoma and hypothyroidism. However, larger scale studies with better phenotype classification, longer follow‐up and taking comorbidity and other biases into consideration are needed to address a potential causal relationship.
Monocyte and lymphocyte surface molecules in severe sepsis and non‐septic critically ill Patients
Authors: Jämsä Joel , Syrjälä Hannu , Huotari Virva , Savolainen Eeva‐Riitta , Ala‐Kokko Tero
Published: February 2017

The aim of the present study was to investigate whether expression of monocyte and lymphocyte surface molecules differs between patients with severe sepsis and non‐septic patients treated in the intensive care unit (ICU). The expression of monocyte CD14, CD40, CD80 and HLA‐DR, and lymphocyte CD69 were analyzed using quantitative flow cytometry on three consecutive days in 27 patients with severe sepsis and in 15 non‐septic patients. Receiver operating characteristic analyses were performed and each corresponding area under the curve (AUC) was determined. The results showed that the expression levels of CD40 on monocytes and CD69 on CD4+ T cells and on natural killer (NK) cells were highest in patients with severe sepsis (p < 0.05). Monocyte CD40 and NK cell CD69 expression levels were higher in patients with severe sepsis and positive blood culture compared with those with negative blood culture (p < 0.05). The highest values of AUC for severe sepsis detection were 0.836 for CD40, 0.872 for CD69 on NK cells, and 0.795 for CD69 on CD4+ T cells. These findings suggest that monocyte CD40 and CD69 on NK cells and CD4+ T cells could prove useful for new approaches in the identification of severe sepsis in the ICU.
Editorial: can we get more clinical benefit from thiopurine metabolite testing?
Authors: Fraser A. G.
Published: February 2017

Linked Content

This article is linked to Wong and Coenen et al and Hooymans papers. To view these articles visit https://doi.org/10.1111/apt.13879 and https://doi.org/10.1111/apt.13955.
Letter: refractory coeliac disease and coeliac‐specific serology status – authors’ reply
Authors: Eigner W. , Vogelsang H.
Published: February 2017

Linked Content

This article is linked to Eigner and Bashir et al and Matuchansky papers. To view these articles visit https://doi.org/10.1111/apt.13867 and https://doi.org/10.1111/apt.13941.
Higher infliximab trough levels are associated with perianal fistula healing in patients with Crohn's disease
Authors: Yarur A. J. , Kanagala V. , Stein D. J. , Czul F. , Quintero M. A. , Agrawal D. , Patel A. , Best K. , Fox C. , Idstein K. , Abreu M. T.
Published: February 2017

Background

Infliximab has been found to be efficacious in the treatment of fistulas in the setting of Crohn's disease, even though some patients do not benefit from therapy.

Aim

To assess the correlation between perianal fistula healing and trough levels of infliximab.

Methods

In this cross‐sectional study, we identified patients with Crohn's disease who had perianal fistulas and were treated with infliximab for at least 24 weeks. We excluded patients who underwent a faecal diversion procedure or proctectomy. Predictive variables included demographics, disease phenotype, disease activity, infliximab levels, anti‐infliximab antibodies. The primary outcome was fistula healing defined as the absence of drainage. The secondary outcome was complete fistula closure and mucosal healing.

Results

117 patients were included. Patients with fistula healing had significantly higher median serum infliximab levels when compared to those with active fistulas [15.8 vs. 4.4 μg/mL, respectively (P < 0.0001)]. There was an incremental gain in fistula healing with higher infliximab levels. The AUC for the association between fistula healing and infliximab levels was 0.82 (P < 0.0001), while the AUC for the association of infliximab levels and fistula closure was 0.69 (P = 0.014). Patients with anti‐infliximab antibodies had a lower chance of achieving fistula healing (OR: 0.04 [95%CI: 0.005–0.3], P < 0.001).

Conclusions

There is a significant association between serum infliximab levels and rates of fistula healing. Achieving infliximab levels ≥10.1 mcg/mL in patients with Crohn's disease and perianal fistulas may improve outcomes as part of a treat‐to‐target strategy.
Differential effects of dominant and subordinate plant species on the establishment success of target species in a grassland restoration experiment
Authors: Torrez Vania , Mergeay Joachim , Meester Luc De , Honnay Olivier , Helsen Kenny
Published: February 2017

Questions

We investigated how the establishment of sown target species for ecological restoration is affected by the early introduction of either dominant or subordinate species during the assembly of a restored topsoil‐stripped, nutrient‐poor grassland. Do dominant or subordinate species exert different priority effects on either wanted target species or unwanted pioneer species? If priority effects are detected, are these exerted via niche preemption or niche modification mechanisms? Are the resulting patterns of species establishment related to differences in functional trait composition?

Location

Meerdaal forest, Oud‐Heverlee, Belgium.

Methods

A 2‐yr field experiment on a topsoil‐stripped site of 8.5 ha was carried out. We manipulated the early arrival of dominant and subordinate species. The ‘dominant species’ set consisted of three generalist grass species, and the ‘subordinate species’ set consisted of nine species of forbs and graminoids that often occur in nutrient‐poor grasslands. After 4 wk, we sowed nine target species for ecological restoration. We recorded plant species cover during 2 yr. We used repeated measures ANOVA to test for effects of time (2013, 2014) and treatment (dominant, subordinate and control) on plant species richness, evenness, cover, functional diversity and species and trait composition dissimilarity.

Results

Both dominant and subordinate species successfully suppressed undesirable early colonizing species. Dominants did not exert priority effects on target species. However, subordinate species exerted strong priority effects via niche preemption, and suppressed their establishment of target species.

Conclusions

Manipulating the arrival order of dominant species has potential as a restoration tool that can allow restoration practitioners to enhance the establishment success of target species for restoration. We suggest that seed mixtures for restoration should contain dominant species, because they will not affect the establishment of subordinate (target) species, but will impede the establishment of unwanted pioneer and ruderal species. We also demonstrate that implementing trait‐based measures in restoration projects can help to adequately predict assembly processes.
Neonatal Exposure to Endocrine Disrupting Chemicals Impairs Learning Behaviour by Disrupting Hippocampal Organization in Male Swiss Albino Mice
Authors: Bhaskar Rakesh , Mishra Ashish K. , Mohanty Banalata
Published: February 2017

Hippocampus is highly susceptible to endocrine disrupting chemicals exposure particularly during the critical phase of brain development. In this study, mice offspring were exposed to endocrine disruptors mancozeb (MCZ) and imidacloprid (IMI) individually (40 mg MCZ and 0.65 mg IMI/kg/day) as well as to their equimixture (40 mg MCZ + 0.65 mg IMI/kg/day) through the diet of lactating mothers from post‐natal day (PND) 1 to PND 28. Half of the randomly selected male offspring were killed at PND 29, and the rest half were left unexposed and killed at PND 63. Brain weight, histology, plasma hormone profile and working memory performance were the various end‐points studied. Brain weight was significantly decreased in the mixture‐exposed group at PND 29, which persisted to PND 63. Total thickness of pyramidal cell layers decreased significantly along with misalignment, shrinkage and degeneration of pyramidal neurons in CA1 and CA3 regions of the IMI and mixture‐exposed groups. The length and branch points of dendrites of pyramidal neurons were decreased significantly in mixture‐exposed group at both PND 29 and PND 63. Dendritic spine density was also reduced in mixture‐exposed group offspring. Testosterone level was significantly decreased only at PND 29, but corticosterone level was increased at both PND 29 and PND 63 in mixture‐exposed offspring. T‐maze task performance revealed significantly increased time duration and reduced path efficiency in mixture‐exposed group offspring. The results thus indicate that pesticide mixture exposure could lead to changes in learning behaviour even at doses that individually did not induce any adverse effect on hippocampal organization.
Semiparametric Regression Analysis of Interval-Censored Competing Risks Data
Authors: Mao Lu , Lin Dan-Yu , Zeng Donglin
Published: February 2017

Interval-censored competing risks data arise when each study subject may experience an event or failure from one of several causes and the failure time is not observed directly but rather is known to lie in an interval between two examinations. We formulate the effects of possibly time-varying (external) covariates on the cumulative incidence or sub-distribution function of competing risks (i.e., the marginal probability of failure from a specific cause) through a broad class of semiparametric regression models that captures both proportional and non-proportional hazards structures for the sub-distribution. We allow each subject to have an arbitrary number of examinations and accommodate missing information on the cause of failure. We consider nonparametric maximum likelihood estimation and devise a fast and stable EM-type algorithm for its computation. We then establish the consistency, asymptotic normality, and semiparametric efficiency of the resulting estimators for the regression parameters by appealing to modern empirical process theory. In addition, we show through extensive simulation studies that the proposed methods perform well in realistic situations. Finally, we provide an application to a study on HIV-1 infection with different viral subtypes.
A General Statistical Framework for Subgroup Identification and Comparative Treatment Scoring
Authors: Chen Shuai , Tian Lu , Cai Tianxi , Yu Menggang
Published: February 2017

Many statistical methods have recently been developed for identifying subgroups of patients who may benefit from different available treatments. Compared with the traditional outcome-modeling approaches, these methods focus on modeling interactions between the treatments and covariates while by-pass or minimize modeling the main effects of covariates because the subgroup identification only depends on the sign of the interaction. However, these methods are scattered and often narrow in scope. In this article, we propose a general framework, by weighting and A-learning, for subgroup identification in both randomized clinical trials and observational studies. Our framework involves minimum modeling for the relationship between the outcome and covariates pertinent to the subgroup identification. Under the proposed framework, we may also estimate the magnitude of the interaction, which leads to the construction of scoring system measuring the individualized treatment effect. The proposed methods are quite flexible and include many recently proposed estimators as special cases. As a result, some estimators originally proposed for randomized clinical trials can be extended to observational studies, and procedures based on the weighting method can be converted to an A-learning method and vice versa. Our approaches also allow straightforward incorporation of regularization methods for high-dimensional data, as well as possible efficiency augmentation and generalization to multiple treatments. We examine the empirical performance of several procedures belonging to the proposed framework through extensive numerical studies.
Utah obstetricians’ opinions of planned home birth and conflicting NICE/ACOG guidelines: A qualitative study
Authors: Rainey Emily , Simonsen Sara , Stanford Joseph , Shoaf Kimberley , Baayd Jami
Published: February 2017

Background

The United Kingdom's National Institute for Health and Care Excellence (NICE) recently published recommendations that support planned home birth for low‐risk women. The American College of Obstetricians and Gynecologists (ACOG) remains wary of planned home birth, asserting that hospitals and birthing centers are the safest birth settings. Our objective was to examine opinions of obstetricians in Salt Lake City, Utah about home birth in the context of rising home birth rates and conflicting guidelines.

Methods

Participants were recruited through online searches of Salt Lake City obstetricians and through snowball sampling. We conducted individual interviews exploring experiences with and attitudes toward planned home birth and the ACOG/NICE guidelines.

Results

Fifteen obstetricians who varied according to years of experience, location of medical training, sex, and subspecialty (resident, OB/GYN, maternal‐fetal medicine specialist) were interviewed. Participants did not recommend home birth but supported a woman's right to choose her birth setting. Obstetrician opinions about planned home birth were shaped by misconceptions of home birth benefits, confusion surrounding the scope of care at home and among home birth providers, and negative transfer experiences. Participants were unfamiliar with the literature on planned home birth and/or viewed the evidence as unreliable. Support for ACOG guidelines was high, particularly in the context of the United States health care setting.

Conclusion

Physician objectivity may be limited by biases against home birth, which stem from limited familiarity with published evidence, negative experiences with home‐to‐hospital transfers, and distrust of home birth providers in a health care system not designed to support home birth.
Changing priorities in physical geography: Introduction to the Special Issue
Authors: Tadaki Marc , Slaymaker Olav , Martin Yvonne
Published: February 2017

Key Messages

The disappearance of the sub‐discipline of physical geography is both notable and regrettable.

This Special Issue provides a forum to describe changes across the environmental sciences, and Geography provides a set of values with which to evaluate these changes.

For physical geography to continue to exist, we must produce physical geographers who identify as geographers and who engage in geographical discourse.
Evaluation of the enhanced permeability and retention effect in the early stages of lymph node metastasis
Authors: Mikada Mamoru , Sukhbaatar Ariunbuyan , Miura Yoshinobu , Horie Sachiko , Sakamoto Maya , Mori Shiro , Kodama Tetsuya
Published: February 2017

Most solid cancers spread to new sites via the lymphatics before hematogenous dissemination. However, only a small fraction of an intravenously administered anti‐cancer drug enters the lymphatic system to reach metastatic lymph nodes (LN). Here, we show that the enhanced permeability and retention (EPR) effect is not induced during the early stages of LN metastasis. Luciferase‐expressing tumor cells were injected into the subiliac LN of the MXH10/Mo‐lpr/lpr mouse to induce metastasis to the proper axillary LN (PALN). In vivo biofluorescence imaging was used to confirm metastasis induction and to quantify the EPR effect, measured as PALN accumulation of intravenously injected indocyanine green (ICG) liposomes. PALN blood vessel volume changes were measured by contrast‐enhanced high‐frequency ultrasound imaging. The volume and density of blood vessels in the PALN increased until day 29 after inoculation, whereas the LN volume remained constant. ICG retention was first detected on day 29 post‐inoculation. While CD31‐positive cells increased up to day 29 post‐inoculation, α‐smooth muscle actin‐positive cells were detected on day 29 post‐inoculation for the first time. These results suggest that the EPR effect was not induced in the early stages of LN metastasis; therefore, systemic chemotherapy would likely not be beneficial during the early stages of LN metastasis. The development of an alternative drug delivery system, independent of the EPR effect, is required for the treatment of LN metastasis.
Thirty‐day outcomes for children and adolescents undergoing laparoscopic sleeve gastrectomy at a free‐standing children's hospital
Authors: Speer A. L. , Parekh J. , Qureshi F. G. , Nadler E. P.
Published: February 2017

The obesity epidemic continues to affect millions of children and adolescents. Non‐surgical options do not result in significant or sustained weight loss; thus bariatric surgery has become increasingly utilized. Limited data exist regarding safety for paediatric bariatric surgery, especially outside of National Institutes of Health (NIH)‐funded centres. We hypothesized that the perioperative outcomes of paediatric patients undergoing laparoscopic sleeve gastrectomy (LSG) at our free‐standing children's hospital would provide adequate safety profiles. We retrospectively reviewed demographics, comorbidities and 30‐d outcomes for all patients who underwent LSG from 2010 to 2015 at a free‐standing children's hospital. A total of 105 patients underwent 107 LSG procedures (two revisions). Mean age was 17.2 ± 2.4 years. Male to female ratio was 1:4. The majority were Black (57.1%), followed by White (21.0%) and Hispanic (18.1%). The mean body mass index was 51.0 ± 9.8 kg/m2. Comorbidities included obstructive sleep apnea (59.0%), hypertension (15.2%), polycystic ovarian disease (16.7% of females only), depression (12.4%) and diabetes (11.4%). Median length of stay was 2.0 d (1–7 d). There were no deaths. Major complications occurred in four patients (3.8%); three required reoperation. Four patients (3.8%) experienced minor complications. Laparoscopic sleeve gastrectomy can be safely performed for children and adolescents at a free‐standing children's hospital without NIH‐support.
Sacral neuromodulation compared with injection of bulking agents for faecal incontinence following obstetric anal sphincter injury – a randomized controlled trial
Authors: Rydningen M. , Dehli T. , Wilsgaard T. , Rydning A. , Kumle M. , Lindsetmo R. O. , Norderval S.
Published: February 2017

Aim

The purpose of this trial was to compare the effectiveness of sacral neuromodulation (SNM) with a submucosal injection of collagen (Permacol®) in women with faecal incontinence following obstetric anal sphincter injury (OASIS).

Method

This single‐blinded randomized controlled trial at two hospital units in Norway included women with faecal incontinence following OASIS. Eligible women who had had a successful percutaneous nerve evaluation were randomly assigned to SNM or Permacol®. The primary outcome was the difference in the St Mark's incontinence score between baseline and 6 months. Secondary outcomes were changes in the disease‐specific quality of life (FIQL) and urinary incontinence (ICIQ‐UI‐SF) scores.

Results

Fifty‐eight women were randomly assigned to SNM (n = 30) and Permacol® (n = 28). The reduction in the St Mark's score between baseline and 6 months was 11.2 (SD 5.3) in the SNM group vs 2.3 (SD 5.0) in the Permacol® group, resulting in a difference of 8.9 (95% CI: 6.1–11.7, P < 0.0001). The differences in the four scales of FIQL (lifestyle, coping, depression, embarrassment) were 0.90 (95% CI: 0.50–1.30, P < 0.001), 1.05 (0.62–1.47, P < 0.001), 0.52 (95% CI: 0.16–0.87, P = 0.005) and 0.95 (95% CI: 0.50–1.40, P < 0.001), respectively, in favour of SNM. The difference in the ICIQ‐UI‐SF was 5.0 (95% CI: 1.97–8.02, P = 0.002) in favour of SNM. There were nine minor adverse events in the SNM group compared with seven in the Permacol® group (P = 0.77).

Conclusion

SNM was superior to Permacol® in terms of reduction of St Mark's score, ICIQ‐UI‐SF and the change of the FIQL in women with faecal incontinence following OASIS.
Panda Downlisted but not Out of the Woods
Authors: Swaisgood Ronald R. , Wang Dajun , Wei Fuwen
Published: February 2017

The giant panda (Ailuropoda melanoleuca) is no longer Endangered on the International Union for the Conservation of Nature's (IUCN) storied Red List. The decision to downlist the panda to Vulnerable has its foundation in a systematic assessment of population parameters as determined by China State Forestry Administration's circa decadal national survey and other scientific outputs, compared to standardized criteria used by IUCN to determine the status of all species. This decision has not been without controversy and disagreement, perhaps reflecting disparities between how people view the term “Endangered” and the criteria established by the IUCN. Here, we explore the architecture of recovery of this iconic “Endangered” species, make transparent the process of the IUCN downlisting decision, evaluate emerging threats to pandas on the horizon, and contemplate the meaning of this milestone for endangered species conservation. Through this revelation, we find profound reasons for hope for species conservation everywhere, and a useful example of success in the making. However, this positive message comes with measured caution. The Chinese government and conservation community must maintain its focus and investment on panda conservation, and contend with strategies to address new threats. If they do not, the panda will return to “Endangered” status once again.
Genital folliculo‐sebaceous cystic hamartoma: A claim of the stroma as a clue in the diagnosis of proliferations with follicular differentiation
Authors: Alegría‐Landa Victoria , Jo‐Velasco Margarita , Prieto‐Torres Lucía , Requena Luis
Published: February 2017

Folliculo‐sebaceous hamartomas comprise a series of entities whose boundaries are imprecise. We present the clinical case of a folliculo‐sebaceous cystic hamartoma of genital localization where the diagnosis was established based on the epithelial proliferation, but mostly, on the characteristic stroma. Because this lesion lacked of the cystic component, we mention the most frequent differential diagnoses and review the literature of the few cases published on this infrequent localization.
Smoking prevalence among lesbian, bisexual and queer women in Sydney remains high: Analysis of trends and correlates
Authors: Deacon Rachel M. , Mooney‐Somers Julie
Published: February 2017

Introduction and Aims

To investigate smoking prevalence trends and correlates among lesbian, bisexual and queer‐identifying (LBQ) women in Sydney, Australia.

Design and Methods

Data from 5007 respondents to a repeated cross‐sectional community survey were used to examine smoking trends between 2004 and 2014. Multinomial logistic regression was used to examine smoking correlates.

Results

Thirty percent of respondents were current smokers, including 48% of 16 to 24‐year‐olds. A slight decrease in all‐ages smoking over time was not reflected in the youngest age group. LBQ women who smoke have fewer economic, social and psychological resources than both women who never smoke and ex‐smokers. High levels of alcohol and illicit drug use are also correlated with current smoking.

Discussion and Conclusions

Population‐wide interventions have failed to address the persistently high prevalence of smoking among this sample of LBQ women. Tailored interventions may find utility focusing on personal resilience to deal with general and sexuality‐specific stressors, as well as attending to poly‐substance use. Acknowledgment of LBQ women as a priority group for tobacco reduction is urgently needed. We call on tobacco control agencies to consider sexuality and gender orientation in policy and partner with lesbian, gay, bisexual and transgender community organisations to develop culturally appropriate interventions. [Deacon RM, Mooney‐Somers J Smoking prevalence among lesbian, bisexual and queer women in Sydney remains high: Analysis of trends and correlates Drug Alcohol Rev 2017;36:546‐554]
Comparison of procedural sequences in same‐day painless bidirectional endoscopy: Single‐center, prospective, randomized study
Authors: Cao Yan , Yang Jun , Li Jiao , Ao Xin , Zhang Kai‐Yuan , Shen Xiao‐Chun , Chen Dong‐Feng , Lan Chun‐Hui
Published: February 2017

Background and Aim

To compare the efficacy and safety of esophagogastroduodenoscopy (EGD)‐colonoscopy and colonoscopy‐EGD sequences for patients subjected to same‐day bidirectional endoscopy under remifentanil and propofol sedation.

Methods

A total of 209 eligible outpatients scheduled for diagnostic same‐day bidirectional endoscopy between 16 February 2016 and 30 April 2016 were randomly assigned to the EGD‐colonoscopy (n = 106) and colonoscopy‐EGD (n = 103) sequence groups. Primary endpoint was total dose of propofol required for the procedure. Secondary endpoints included duration of endoscopy, patient satisfaction, adverse effects, endoscopy findings, and cardiopulmonary responses of the patients.

Results

Patients in the two groups were similar in terms of demographic and clinical data (P > 0.05). EGD‐colonoscopy sequence group had lesser requirement of propofol for sedation (P < 0.05), faster recovery (P < 0.001), and lesser influence on mean arterial pressure (MAP) during the endoscopy (P < 0.05). Duration of EGD and colonoscopy, patient satisfaction, adverse effects, and pathological findings did not differ between the two groups.

Conclusions

The EGD‐colonoscopy sequence may be considered the preferred sequence for same‐day bidirectional endoscopy as a result of less cardiovascular stress, lessened need for sedation with propofol, and faster recovery.
From prioritizing objects to prioritizing cues: a developmental shift for cognitive control
Authors: Chevalier Nicolas , Dauvier Bruno , Blaye Agnès
Published: February 2017

Emerging cognitive control supports increasingly adaptive behaviors and predicts life success, while low cognitive control is a major risk factor during childhood. It is therefore essential to understand how it develops. The present study provides evidence for an age‐related shift in the type of information that children prioritize in their environment, from objects that can be directly acted upon to cues signaling how to act. Specifically, gaze patterns recorded while 3‐ to 12‐year‐olds and adults engaged in a cognitive control task showed that whereas younger children fixated on targets that they needed to respond to before gazing at task cues signaling how to respond, older children and adults showed the opposite pattern (which yielded better performance). This shift in information prioritization has important conceptual implications, suggesting that a major force behind cognitive control development may be non‐executive in nature, as well as opening new directions for interventions.