bluuebunny/crossref_metadata_2025 huggingface dataset:
Depth and Patterns of Adnexal Involvement in Primary Extramammary (Anogenital) Paget Disease: A Study of 178 Lesions From 146 Patients
Authors: Konstantinova Anastasia M. , Shelekhova Ksenya V. , Stewart Colin J. , Spagnolo Dominic V. , Kutzner Heinz , Kacerovska Denisa , Plaza Jose A. , Suster Saul , Bouda Jiri , Pavlovsky Michal , Kyrpychova Liubov , Michal Michal , Guenova Emmanuella , Kazakov Dmitry V.
Published: February 2016

Extramammary Paget disease (EMPD) is a rare neoplasm usually presenting in the anogenital area, most commonly in the vulva. Adnexal involvement in primary EMPD is a very common feature and serves as a pathway for carcinoma to spread into deeper tissue. The depth of carcinomatous spread along the appendages and the patterns of adnexal involvement were studied in 178 lesions from 146 patients with primary EMPD. Hair follicles and eccrine ducts were the adnexa most commonly affected by carcinoma cells. The maximal depth of involvement was 3.6 mm in this series. When planning topical therapy or developing novel local treatment modalities for EMPD, this potential for significant deep spread along adnexa should be taken into account.
Syringocystadenocarcinoma Papilliferum In Situ–Like Changes in Extramammary Paget Disease: A Report of 11 Cases
Authors: Konstantinova Anastasia M. , Kacerovska Denisa , Stewart Colin J. R. , Szepe Peter , Pitha Jan , Sulc Miroslav , Bencik Vladimir , Michal Michal , Shideler Barbara , Kerl Katrin , Kazakov Dmitry V.
Published: February 2016

The authors report 11 cases of extramammary Paget disease (EMPD), all of which also demonstrated a combination of histological changes highly reminiscent of syringocystadenocarcinoma papilliferum in situ. In addition to the classical features of EMPD, characterized by the intraepidermal spread of individually dispersed neoplastic cells with ample cytoplasm, many of which contained mucin, there were areas of acanthosis with the substitution of spinous layer keratinocytes by neoplastic cells, whereas the native basal cell layer was intact. In addition to acanthosis (and sometimes papillomatosis), the dermal papillae showed a prominent infiltrate of plasma cells, completing the resemblance to syringocystadenocarcinoma papilliferum in situ; this similarity was further enhanced in 2 cases, which showed conspicuous gland formation. One additional case showed multifocal dermal proliferations compatible with eccrine syringofibroadenoma (syringofibroadenomatous hyperplasia). The changes described herein seem to be relatively rare in EMPD, and they can represent a diagnostic pitfall, as evidenced by 2 cases that were originally misinterpreted as syringocystadenocarcinoma papilliferum in situ. Clinically, these microscopic changes sometimes corresponded to nodular lesions, which were specifically noted to have a papillated erosive surface.
The work-based predictors of job engagement and job satisfaction experienced by community health professionals
Authors: Noblet Andrew J. , Allisey Amanda F. , Nielsen Ingrid L. , Cotton Stacey , LaMontagne Anthony D. , Page Kathryn M.
Published: February 2016

Background:

Job engagement represents a critical resource for community-based health care agencies to achieve high levels of effectiveness. However, studies examining the organizational sources of job engagement among health care professionals have generally overlooked those workers based in community settings.

Purpose:

This study drew on the demand–control model, in addition to stressors that are more specific to community health services (e.g., unrewarding management practices), to identify conditions that are closely associated with the engagement experienced by a community health workforce. Job satisfaction was also included as a way of assessing how the predictors of job engagement differ from those associated with other job attitudes.

Methodology/Approach:

Health and allied health care professionals (n = 516) from two Australian community health services took part in the current investigation. Responses from the two organizations were pooled and analyzed using linear multiple regression.

Findings:

The analyses revealed that three working conditions were predictive of both job engagement and job satisfaction (i.e., job control, quantitative demands, and unrewarding management practices). There was some evidence of differential effects with cognitive demands being associated with job engagement, but not job satisfaction.

Practice Implications:

The results provide important insights into the working conditions that, if addressed, could play key roles in building a more engaged and satisfied community health workforce. Furthermore, working conditions like job control and management practices are amenable to change and thus represent important areas where community health services could enhance the energetic and motivational resources of their employees.
Changes in Tear Film Characteristics in Patients With Idiopathic Dacryoadenitis
Authors: Xue Kang , Ren Hui , Liu Ailin , Qian Jiang
Published: February 2016

Purpose:

To evaluate the tear-film meniscus with optical coherence tomography (OCT) in patients with idiopathic dacryoadenitis and to determine its relationships with the clinical tests.

Methods:

Sixteen patients with unilateral idiopathic dacryoadenitis were included in the study. Patients with idiopathic dacryoadenitis with affected sites (group 1), with contralateral sites (group 2) and healthy participants (group 3) completed the ocular surface disease index before optical coherence tomography determination of tear meniscus height and tear meniscus area. These were followed by measurements of tear breakup time, fluorescein staining, and Schirmer test. Finally, surgical debulking or incisional biopsies were conducted.

Results:

Tear meniscus height and tear meniscus area were the lowest in patients with affected sites (group 1) among the 3 groups (p < 0.05). Breakup time was the shortest in group 1 (p < 0.05). In the group 1, breakup time, fluorescein staining score, and histopathological phases were significantly correlated with tear meniscus height and tear meniscus area (p < 0.05).

Conclusions:

Tear function was significantly disturbed in idiopathic dacryoadenitis. Tear menisci volumes measured by optical coherence tomography may assess the tearing function in patients with idiopathic dacryoadenitis.
Comparison of Two Polypropylene Frontalis Suspension Techniques in 92 Patients With Oculopharyngeal Muscular Dystrophy
Authors: Kalin-Hajdu Evan , Attas-Fox Liat , Huang Xi , Hardy Isabelle , Codère François
Published: February 2016

Purpose:

To compare the functional outcome of the polypropylene trapezoid frontalis suspension with the polypropylene modified Crawford frontalis suspension in a large cohort of patients with oculopharyngeal muscular dystrophy.

Methods:

Retrospective, nonrandomized comparative case series. Patients with oculopharyngeal muscular dystrophy who underwent bilateral polypropylene frontalis suspension were selected for chart review. Main outcome measures were margin reflex distance, duration of surgery, and ptosis recurrence.

Results:

Ninety-two patients qualified for chart review; 39 patients underwent the trapezoid sling and 53 patients the modified Crawford sling. There was no difference in preoperative margin reflex distance or levator function between the 2 surgical groups. Postoperative improvement in margin reflex distance was 2.95 ± 1.56 mm in the trapezoid group compared with 2.85 ± 1.65 mm in the modified Crawford group (p = 0.67). Duration of surgery was 40.49 ± 13.33 minutes in the trapezoid group compared with 53.77 ± 16.04 minutes in the modified Crawford group (p < 0.001). Five percent of eyes in the trapezoid group had ptosis recurrence compared with 13% of eyes in the modified Crawford group (p = 0.07).

Conclusion:

Both polypropylene frontalis suspension techniques generated an equivalent increase in margin reflex distance. However, the trapezoid frontalis suspension required less operative time and trended toward a lower rate of ptosis recurrence.
Compliance With Protective Lens Wear in Anophthalmic Patients
Authors: Neimkin Michael G. , Custer Philip L.
Published: February 2016

Purpose:

To evaluate the frequency of protective lens wear by anophthalmic patients and identify factors that influence compliance.

Methods:

An IRB approved descriptive retrospective chart review of patients undergoing surgery with the senior author (PLC) with an anophthalmic orbit and one remaining sighted eye. Results were tabulated and analyzed using age, indication for procedure, duration of visual symptoms, safety glasses wear, number of postoperative visits, and evidence of new trauma to the remaining eye. All patients underwent counseling on the importance of protective lens wear preoperatively and each subsequent visit.

Results:

Etiologies for loss of the eye in the 132 study patients included trauma (33.3%), blind painful eye (33.3%), congenital disorders (14.4%), adult-onset malignancy (14.4%), and retinoblastoma (4.5%). At the final visit, protective lenses were worn in the following patterns: full-time (55.3%), frequently (11.4%), occasional (6%), and never (28.8%). The regular use of protective eyewear at last visit was more common in patients wearing glasses at presentation (79.7%), than in those who did not (32.9%; p ≤ 0.001). Increased number of office encounters correlated with more frequent use of protective eyewear (p ≤ 0.01). Patient age (p = 0.95), indication for surgery (p = 0.97), and duration of visual loss (p = 0.85) were not predictive of safety glasses wear. Three patients had evidence of subsequent ocular trauma to the remaining eye, with 2 having resultant decrease in acuity; none of these 3 patients wore safety glasses full-time.

Conclusions:

A significant number of anopthalmic patients were not wearing protective lenses at presentation. Overall compliance was poor; but repeated education on the importance of safety glasses appears to improve compliance. Educating referring providers and primary care physicians about the importance of early and repeated counseling is vital to increasing compliance.
Fungus Ball of the Maxillary Sinus Presenting With Epiphora
Authors: Cho Ju Eun , Shim Ji Sung , Kim Jong Yang , Joo Joon Bum , Lee Woo Hyun
Published: February 2016

The authors report a case of fungus ball of the maxillary sinus with bone erosion presenting with epiphora, which was diagnosed after treatment failure using silicone intubation for nasolacrimal duct obstruction. Symptoms of sinus fungus ball are similar to those of chronic bacterial rhinosinusitis, although occasionally asymptomatic. To our knowledge, epiphora has never been reported as a symptom of sinus fungus ball. The purpose of this report is to emphasize the importance of considering sinonasal causes when evaluating epiphora patients, as well as to suggest the use of preoperative CT scans for a more accurate diagnosis and to prevent unnecessary procedures.
Individualized Care in the Radiation Oncology Setting From the Patients’ and Nurses’ Perspectives
Authors: Rose Pauline M.
Published: February 2016

Background:

Radiation oncology nurses engage in individualized supportive care of people undergoing radiotherapy. A primary nursing/collaborative practice framework guides the delivery of individualized care to patients.

Objective:

The aim of this study was to describe and compare patients’ and nurses’ perceptions of individualized care in 2 radiotherapy centers.

Methods:

This cross-sectional, comparative study collected data from patients (n = 173) undergoing curative radiotherapy and their nurses (n = 30), using the Individualized Care scales: patient and nurse.

Results:

Moderate to high levels of individual care were perceived by both patients and nurses. More than a third of the item scores for patients reached the more than 4.5 mean score (13/34 [38.2%]), whereby more than half of the items reached this level for nurses (20/34 [58.8%]). The highest scores for both patients and nurses were in the Decisional Control subscales, and the lowest scores were in the Personal Life subscales. Males rated being treated as individuals significantly higher than did females across the majority of subscales. Patients receiving chemotherapy perceived less acknowledgement of individuality overall. Older nurses (46–70 years) reported acknowledging and supporting patient individuality more than did younger nurses. Nurses perceived greater individualized care than patients for the Personal Life scales (A: p = .001); (B: p = .001) and in the acknowledgement of Decisional Control (p = .001).

Conclusion:

A moderate level of individualized nursing care was perceived by the largely outpatient cohort of patients undergoing radiotherapy.

Implications for Practice:

The model of care in these departments may contribute to patient individuality. Further work into gender differences and those receiving chemotherapy may improve care for these patients.
Conducting a Multisite Education Research Project
Authors: Beischel Kelly P. , Hart Julie , Turkelson Sandra L.
Published: February 2016

Multisite education research projects have many benefits as well as perceived barriers. In this article, we share our experiences with a multisite education research project and the barriers we overcame to reap the benefits. The outcome of our research resulted in increased rigor, role-modeling professional collaboration, and promotion of future multisite education studies. The strategies presented in this article will help alleviate perceived barriers and ameliorate the process of conducting multisite education research studies.
Oligonucleotide-Mediated Genome Editing Provides Precision and Function to Engineered Nucleases and Antibiotics in Plants
Authors: Sauer Noel J. , Narváez-Vásquez Javier , Mozoruk Jerry , Miller Ryan B. , Warburg Zachary J. , Woodward Melody J. , Mihiret Yohannes A. , Lincoln Tracey A. , Segami Rosa E. , Sanders Steven L. , Walker Keith A. , Beetham Peter R. , Schöpke Christian R. , Gocal Greg F.W.
Published: February 2016

Here, we report a form of oligonucleotide-directed mutagenesis for precision genome editing in plants that uses single-stranded oligonucleotides (ssODNs) to precisely and efficiently generate genome edits at DNA strand lesions made by DNA double strand break reagents. Employing a transgene model in Arabidopsis (Arabidopsis thaliana), we obtained a high frequency of precise targeted genome edits when ssODNs were introduced into protoplasts that were pretreated with the glycopeptide antibiotic phleomycin, a nonspecific DNA double strand breaker. Simultaneous delivery of ssODN and a site-specific DNA double strand breaker, either transcription activator-like effector nucleases (TALENs) or clustered, regularly interspaced, short palindromic repeats (CRISPR/Cas9), resulted in a much greater targeted genome-editing frequency compared with treatment with DNA double strand-breaking reagents alone. Using this site-specific approach, we applied the combination of ssODN and CRISPR/Cas9 to develop an herbicide tolerance trait in flax (Linum usitatissimum) by precisely editing the 5′-ENOLPYRUVYLSHIKIMATE-3-PHOSPHATE SYNTHASE (EPSPS) genes. EPSPS edits occurred at sufficient frequency that we could regenerate whole plants from edited protoplasts without employing selection. These plants were subsequently determined to be tolerant to the herbicide glyphosate in greenhouse spray tests. Progeny (C1) of these plants showed the expected Mendelian segregation of EPSPS edits. Our findings show the enormous potential of using a genome-editing platform for precise, reliable trait development in crop plants.
The Whiteway Anarchists in the Twentieth Century: A Transnational Community in the Cotswolds
Authors: Taylor Antony
Published: February 2016

This article traces the later history of the Whiteway anarchist community in Gloucestershire. The sole survivor of the various communal experiments of the latter half of the nineteenth century, the Whiteway colony was a bohemian enclave that attracted political militants, draft‐dodgers, exponents of colonial separatism, and cultural and religious dissidents in exile from Europe. In common with other settlements of this nature in Europe and North America, Whiteway received considerable voyeuristic and prurient attention from the state, police, anti‐vice activists and near neighbours. This article examines the mythology surrounding Whiteway, and considers the arguments about its later significance in the twentieth century. Locating the community in the traditions of political protest, it relates the history of Whiteway to broader debates about the role of alternative cultures within British popular politics and memory. Re‐examining Whiteway's reputation for the exotic and the aberrant, this article unearths previously unused documents about the colony to reassess the changing moral and political attitudes displayed towards the community by reformers and anti‐reformers at the beginning of the twentieth century.
Islam as Europe's ‘Other’ in the Long Term: Some Discontinuities
Authors: Wintle Michael
Published: February 2016

One of the most important aspects of identity – both individual and collective – is the process known as Othering. One of the ways of identifying Europe, then, is through the fact that much of Europe shares its ‘Others’, at least to a degree. There is a partly shared, imagined European heritage of enemies, dangers, different people, alien forces, and threats: prime candidates for this ‘Other’ have been the remaining continents, the colonies, the United States, Communism, and especially Islam. Islam has been a prominent if not dominant ‘Other’ for a very long time, since its rise in the seventh century. It is argued that it has changed radically as an ‘Other’ or type of ‘Other’, and that it is not just an external but an internal ‘Other’. However, longevity (if not continuity) and current pre‐eminence justify the examination of Islam as Europe's ‘Other’ throughout history. A survey of the Islamic European ‘Other’ over the last thirteen centuries or so is followed by two illustrative excursions: the Ottomans as the Islamic ‘Other’, and Islam as an iconic symbol for Asia, which was often Europe's principal ‘Other’ amongst the continents. The article ends with an account of the discontinuities in this process, particularly the difference between Europe as a religious idea in the Middle Ages, and as a civilizational idea since the Renaissance.
Molecular Analysis of the Polymeric Glutenins with Gliadin‐Like Characteristics That Were Produced by Acid Dispersion of Wheat Gluten
Authors: Murakami Tetsuya , Nishimura Takahisa , Kitabatake Naofumi , Tani Fumito
Published: February 2016

We had earlier shown that the dispersion of wheat gluten in acetic acid solution conferred gliadin‐like characteristics to the polymeric glutenins. To elucidate the molecular behavior of its polymeric glutenins, the characteristics of gluten powder prepared from dispersions with various types of acid were investigated in this study. Mixograph measurements showed that the acid‐treated gluten powders, regardless of the type of acid, had dough properties markedly weakened in both resistance and elasticity properties, as though gliadin was supplemented. The polymeric glutenins extracted with 70% ethanol increased greatly in all acid‐treated gluten powders. Size exclusion HPLC and SDS‐PAGE indicated that the behavior of polymeric glutenins due to acid treatment was attributed to their subunit composition rich in high molecular weight glutenin subunit (HMW‐GS) and not their molecular size. The gluten prepared with the addition of NaCl in acid dispersion had properties similar to those of the control gluten. The results suggest that ionic repulsion induced by acid dispersion made the polymeric glutenins rich in HMW‐GS disaggregate, and therefore, act like gliadins.
The Road to NHDPlus — Advancements in Digital Stream Networks and Associated Catchments
Authors: Moore Richard B. , Dewald Thomas G.
Published: February 2016

A progression of advancements in Geographic Information Systems techniques for hydrologic network and associated catchment delineation has led to the production of the National Hydrography Dataset Plus (NHDPlus). NHDPlus is a digital stream network for hydrologic modeling with catchments and a suite of related geospatial data. Digital stream networks with associated catchments provide a geospatial framework for linking and integrating water‐related data. Advancements in the development of NHDPlus are expected to continue to improve the capabilities of this national geospatial hydrologic framework. NHDPlus is built upon the medium‐resolution NHD and, like NHD, was developed by the U.S. Environmental Protection Agency and U.S. Geological Survey to support the estimation of streamflow and stream velocity used in fate‐and‐transport modeling. Catchments included with NHDPlus were created by integrating vector information from the NHD and from the Watershed Boundary Dataset with the gridded land surface elevation as represented by the National Elevation Dataset. NHDPlus is an actively used and continually improved dataset. Users recognize the importance of a reliable stream network and associated catchments. The NHDPlus spatial features and associated data tables will continue to be improved to support regional water quality and streamflow models and other user‐defined applications.
Pediatric rheumatology consultant workforce in Australia and New Zealand: the current state of play and challenges for the future
Authors: Cox Angela , Piper Sue , Singh‐Grewal Davinder
Published: February 2016

Aim

There have been no formal assessments of current levels of the pediatric rheumatology workforce in Australia and New Zealand. Despite this it is felt that we fall well behind international guidelines placing children and adolescents with rheumatic diseases at risk of suboptimal care. Overcoming this shortfall in specialist pediatric rheumatology care requires documentation and recognition of the shortfall and a commitment from the health system to support improvements to supplement the current specialist workforce. The purpose of this survey was to assess the current state of play of the pediatric rheumatology workforce in Australia and New Zealand.

Methods

The Australian Paediatric Rheumatology Group (APRG) conducted a survey, which examined the current pediatric rheumatology workforce in Australia and New Zealand. The survey was sent via email link to a survey hosted by Zoomerang™ to 49 physicians known to treat patients with pediatric rheumatic diseases and they were asked to forward the survey to any others who they knew saw children with rheumatic disease.

Results

Currently there is a shortfall in the pediatric rheumatology workforce of 68% based on minimum requirements and a shortfall of 225% based on an ideal scenario.

Conclusion

Currently in Australia and New Zealand we fail to provide the level of care to children with pediatric rheumatic diseases comparable to other developed health economies worldwide. The current deficiency requires an increase in resource allocation to clinical service and speciality training to overcome this disparity and ensure children in Australia and New Zealand receive internationally recognized standards of care.
Transanal submucosal polyacrylamide gel injection treatment of anal incontinence: a randomized controlled trial
Authors: Altman Daniel , Hjern Fredrik , Zetterström Jan
Published: February 2016

Introduction

The efficacious and safe use of transurethral injections of polyacrylamide hydrogel (Bulkamid®) in women with stress urinary incontinence suggests that it may be suitable also for treatment of anal incontinence. We aimed to determine the effectiveness and safety of polyacrylamide hydrogel when used as a transanal submucosal bulking agent in women with anal incontinence.

Materials and methods

Thirty women with a diagnosis of anal incontinence and a Cleveland Clinic Incontinence Score (CCIS) >10 were randomized to three different techniques of transanal submucosal injections using polyacrylamide hydrogel. Follow up was performed at 2, 6 and 12 months using CCIS and the Fecal Incontinence Quality of Life scale (FIQL).

Results

In all, 29 of the 30 women completed the follow up. Approximately half of the women requested a re‐injection at the 6‐month visit. The overall CCIS improved significantly from baseline (14.7. SD 2.5) to 1 year (12.4. SD 3.1) (p = 0.003). There was a significant improvement with regard to the occurrence of loose fecal incontinence (p = 0.014) but not for solid fecal incontinence (p = 0.28). At 1 year the FIQL domains of coping‐behavior, depression, and embarrassment showed significant improvements (p = 0.012, p = 0.007 and p = 0.007, respectively). We recorded no adverse events related either to the injection technique or the biomaterial. There were no significant differences between the treatment groups in either CCIS or FIQL scores.

Conclusion

Transanal submucosal injection of polyacrylamide hydrogel resulted in a modest although significant overall improvement in anal incontinence symptom scores with corresponding improvements in several domains of quality of life, regardless of injection volume.
Using a wrap skirt to improve the pelvic examination experience
Authors: Neuhaus Lilian R. , Memeti Elza , Schäffer Marie‐Kristin , Zimmermann Roland , Schäffer Leonhard
Published: February 2016

Introduction

The study aims were to analyze the experience of women and their physicians of nakedness when moving between changing room and examination chair and during pelvic examination itself, and to assess the protective benefit of a wrap skirt in alleviating the associated discomfort and vulnerability.

Material and methods

We offered 1000 women a wrap skirt for pelvic examination and asked them to complete a post‐procedure questionnaire. Physicians were invited to complete a similar but separate questionnaire. Data were analyzed using chi‐squared contingency tables.

Results

A total of 425 women (43%, age 15–78 years) completed the questionnaire; 51% felt uncomfortable and embarrassed during the examination, Muslim women significantly more so (p < 0.001). Most women (n = 255; 58%) rated the wrap skirt a significant improvement; 69% requested it for future examinations, significantly more so if the physician was male rather than female (66% vs. 54%, p = 0.003). Even the one‐third of women experiencing no discomfort reported improvement. Most examiners (n = 45; 56%) found the wrap skirt beneficial; 31 (38%) were unconvinced.

Conclusions

Pelvic examination as practiced in many countries, on women naked from the waist down throughout, causes unnecessary embarrassment. A simple protective measure, such as a wrap skirt, significantly alleviates the discomfort and sense of vulnerability associated with nakedness.
An Information-Theoretic Approach for the Evaluation of Surrogate Endpoints Based on Causal Inference
Authors: Alonso Ariel , Van der Elst Wim , Molenberghs Geert , Buyse Marc , Burzykowski Tomasz
Published: February 2016

In this work a new metric of surrogacy, the so-called individual causal association (ICA), is introduced using information-theoretic concepts and a causal inference model for a binary surrogate and true endpoint. The ICA has a simple and appealing interpretation in terms of uncertainty reduction and, in some scenarios, it seems to provide a more coherent assessment of the validity of a surrogate than existing measures. The identifiability issues are tackled using a two-step procedure. In the first step, the region of the parametric space of the distribution of the potential outcomes, compatible with the data at hand, is geometrically characterized. Further, in a second step, a Monte Carlo approach is proposed to study the behavior of the ICA on the previous region. The method is illustrated using data from the Collaborative Initial Glaucoma Treatment Study. A newly developed and user-friendly R package Surrogate is provided to carry out the evaluation exercise.
A Flexible Ratio Regression Approach for Zero-Truncated Capture–Recapture Counts
Authors: Böhning Dankmar , Rocchetti Irene , Alfó Marco , Holling Heinz
Published: February 2016

Capture–recapture methods are used to estimate the size of a population of interest which is only partially observed. In such studies, each member of the population carries a count of the number of times it has been identified during the observational period. In real-life applications, only positive counts are recorded, and we get a truncated at zero-observed distribution. We need to use the truncated count distribution to estimate the number of unobserved units. We consider ratios of neighboring count probabilities, estimated by ratios of observed frequencies, regardless of whether we have a zero-truncated or an untruncated distribution. Rocchetti et al. (2011) have shown that, for densities in the Katz family, these ratios can be modeled by a regression approach, and Rocchetti et al. (2014) have specialized the approach to the beta-binomial distribution. Once the regression model has been estimated, the unobserved frequency of zero counts can be simply derived. The guiding principle is that it is often easier to find an appropriate regression model than a proper model for the count distribution. However, a full analysis of the connection between the regression model and the associated count distribution has been missing. In this manuscript, we fill the gap and show that the regression model approach leads, under general conditions, to a valid count distribution; we also consider a wider class of regression models, based on fractional polynomials. The proposed approach is illustrated by analyzing various empirical applications, and by means of a simulation study.
Technical mentorship during robot‐assisted surgery: a cognitive analysis
Authors: Hussein Ahmed A. , Shafiei Somayeh B. , Sharif Mohamed , Esfahani Ehsan , Ahmad Basel , Kozlowski Justen D. , Hashmi Zishan , Guru Khurshid A.
Published: February 2016

Objective

To investigate cognitive and mental workload assessments, which may play a critical role in defining successful mentorship.

Materials and Methods

The ‘Mind Maps’ project aimed at evaluating cognitive function with regard to surgeon's expertise and trainee's skills. The study included electroencephalogram (EEG) recordings of a mentor observing trainee surgeons in 20 procedures involving extended lymph node dissection (eLND) or urethrovesical anastomosis (UVA), with simultaneous assessment of trainees using the National Aeronautics and Space Administration Task Load index (NASA‐TLX) questionnaire. We also compared the brain activity of the mentor during this study with his own brain activity while actually performing the same surgical steps from previous procedures populated in the ‘Mind Maps’ project.

Results

During eLND and UVA, when the mentor thought the trainee's mental demand and effort were low based on his NASA‐TLX questionnaire (not satisfied with his performance), his EEG‐based mental workload increased (reflecting more concern and attention). The mentor was mentally engaged and concerned while he was engrossed in observing the surgery. This was further supported by the finding that there was no significant difference in the mental demands and workload between observing and operating for the expert surgeon.

Conclusions

This study objectively evaluated the cognitive engagement of a surgical mentor teaching technical skills during surgery. The study provides a deeper understanding of how surgical teaching actually works and opens new horizons for assessment and teaching of surgery. Further research is needed to study the feasibility of this novel concept in assessment and guidance of surgical performance.
Discovery of Novel Allosteric Eg5 Inhibitors Through Structure‐Based Virtual Screening
Authors: Zhang Wei , Zhai Ling , Lu Wenyan , Boohaker Rebecca J. , Padmalayam Indira , Li Yonghe
Published: February 2016

Mitotic kinesin Eg5 is an attractive anticancer drug target. Discovery of Eg5 inhibitors has been focused on targeting the ‘monastrol‐binding site’. However, acquired drug resistance has been reported for such inhibitors. Therefore, identifying new Eg5 inhibitors which function through a different mechanism(s) could complement current drug candidates and improve drug efficacy. In this study, we explored a novel allosteric site of Eg5 and identified new Eg5 inhibitors through structure‐based virtual screening. Experiments with the saturation‐transfer difference NMR demonstrated that the identified Eg5 inhibitor SRI35566 binds directly to Eg5 without involving microtubules. Moreover, SRI35566 and its two analogs significantly induced monopolar spindle formation in colorectal cancer HCT116 cells and suppressed cancer cell viability and colony formation. Together, our findings reveal a new allosteric regulation mechanism of Eg5 and a novel drug targeting site for cancer therapy.
Serum microRNAs as novel biomarkers for primary sclerosing cholangitis and cholangiocarcinoma
Authors: Bernuzzi F , Marabita F , Lleo A , Carbone M , Mirolo M , Marzioni M , Alpini G , Alvaro D , Boberg K M , Locati M , Torzilli G , Rimassa L , Piscaglia F , He X-S , Bowlus C L , Yang G-X , Gershwin M E , Invernizzi P
Published: February 2016

The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC. The levels of 667 miRNAs were evaluated in 90 human serum samples (30 PSC, 30 CC and 30 control subjects) to identify disease-associated candidate miRNAs (discovery phase). The deregulated miRNAs were validated in an independent cohort of 140 samples [40 PSC, 40 CC, 20 primary biliary cirrhosis (PBC) and 40 controls]. Receiver operating characteristic (ROC) curves were established and only miRNAs with an area under the curve (AUC) > 0·70 were considered useful as biomarkers. In the discovery phase we identified the following: 21 miRNAs expressed differentially in PSC, 33 in CC and 26 in both in comparison to control subjects as well as 24 miRNAs expressed differentially between PSC and CC. After the validation phase, miR-200c was found to be expressed differentially in PSC versus controls, whereas miR-483-5p and miR-194 showed deregulated expression in CC compared with controls. We also demonstrate a difference in the expression of miR-222 and miR-483-5p in CC versus PSC. Combination of these specific miRNAs further improved the specificity and accuracy of diagnosis. This study provides a basis for the use of miRNAs as biomarkers for the diagnosis of PSC and CC.
Decision‐making for non‐invasive prenatal testing for Down syndrome: Hong Kong Chinese women's preferences for individual vs relational autonomy
Authors: Lau J.Y.C. , Yi H. , Ahmed S.
Published: February 2016

Individual autonomy in antenatal screening is internationally recognized and supported. Policy and practice guidelines in various countries place emphasis on the woman's right to make her own decision and are related to concepts such as self‐determination, independence, and self‐sufficiency. In contrast, the dominant perspective in Chinese medical ethics suggests that the family is pivotal in making medical decisions, hence providing support for relational autonomy. This study explored Hong Kong Chinese pregnant women's preferences for individual vs relational autonomy for non‐invasive prenatal testing (NIPT) for Down syndrome. A qualitative study was carried out using semi‐structured interviews with 36 women who had undertaken NIPT in Hong Kong. The findings show that most Hong Kong Chinese women valued aspects of both relational and individual autonomy in decision‐making for NIPT. Women expected support from doctors as experts on the topic and wanted to involve their husband in decision‐making while retaining control over the outcome. Somewhat surprisingly, the findings do not provide support for the involvement of family members in decision‐making for NIPT. The adequacy of current interpretations of autonomy in prenatal testing policies as an individual approach needs discussion, where policy developers need to find a balance between individual and relational approaches.
Identification of a founder BRCA1 mutation in the Moroccan population
Authors: Quiles F. , Teulé À. , Martinussen Tandstad N. , Feliubadaló L. , Tornero E. , del Valle J. , Menéndez M. , Salinas M. , Wethe Rognlien V. , Velasco A. , Izquierdo A. , Capellá G. , Brunet J. , Lázaro C.
Published: February 2016

Breast cancer (BC) is the most frequent cancer among women in Morocco. However, the role of the most prevalent BC‐predisposing genes, BRCA1 and BRCA2, has been largely unexplored. To help define the role of BRCA1 in BC in Morocco, we characterized the first potential BRCA1 founder mutation in this population. Genetic testing of BRCA1 and BRCA2 in BC high‐risk families identified mutation BRCA1 c.5309G>T, p.(Gly1770Val) or G1770V in five independent families from Morocco, suggesting a founder effect. To confirm this hypothesis, haplotype construction was performed using seven intragenic and flanking BRCA1 microsatellite markers. Clinical data were also compiled. Clinical data from carriers of mutation G1770V correspond to data from carriers of BRCA1 pathogenic mutations. Microsatellite analysis showed a common haplotype for the five families in a region comprising 1.54 Mb, confirming G1770V as the first specific founder BRCA1 mutation in the Moroccan population. Our findings contribute to a better understanding of BC genetics in the Moroccan population. Nevertheless, comprehensive studies of mutation G1770V in large series of BC patients from Morocco are needed to assess the real prevalence of this mutation and to improve genetic testing and risk assessment in this population.
Advantages of magnifying narrow‐band imaging for diagnosing colorectal cancer coexisting with sessile serrated adenoma/polyp
Authors: Chino Akiko , Osumi Hiroki , Kishihara Teruhito , Morishige Kenjiro , Ishikawa Hirotaka , Tamegai Yoshiro , Igarashi Masahiro
Published: February 2016

Background and Aim

In the present study, we investigated the advantages of narrow‐band imaging (NBI) for efficient diagnosis of sessile serrated adenoma/polyp (SSA/P). The main objective of this study was to analyze the characteristic features of cancer coexisting with serrated lesion by carrying out NBI.

Methods

We evaluated 264 non‐malignant serrated lesions by using three modalities (conventional white light colonoscopy, magnifying chromoendoscopy, and magnifying NBI). Of the evaluated cancer cases with serrated lesions, 37 fulfilled the inclusion criteria.

Results

In diagnosing non‐malignant SSA/P, an expanded crypt opening (ECO) under magnifying NBI is a useful sign. One hundred and twenty‐five lesions (87%) of observed ECO were, at the same time, detected to have type II open pit pattern, which is known to be a valuable indicator when using magnifying chromoendoscopy. ECO had high sensitivity of 80% for identifying SSA/P, with 62% specificity and 83% positive predictive value (PPV). In detecting the cancer with SSA/P, irregular vessels under magnifying NBI were frequently observed with 100% sensitivity and 99% specificity, 86% PPV and 100% negative predictive value.

Conclusions

A focus on irregular vessels in serrated lesions might be useful for identification of cancer with SSA/P. This is an advantage of carrying out magnifying NBI in addition to being used simultaneously with other modalities by switching, and observations can be made by using wash‐in water alone. We can carry out advanced examinations for selected lesions with irregular vessels. To confirm cancerous demarcation and invasion depth, a combination of all three aforementioned modalities should be done.
Leukodystrophies and genetic leukoencephalopathies in childhood: a national epidemiological study
Authors: Stellitano Lesley A , Winstone Anne Marie , van der Knaap Marjo S , Verity Christopher M
Published: February 2016

Aim

To report on the epidemiology of the brain white matter disorders of children identified via a national prospective study.

Method

Since 1997 a study of UK children with progressive intellectual and neurological deterioration (PIND) has used the British Paediatric Surveillance Unit system to identify children with progressive neurodegenerative disease. This paper reports on children in the study with brain white matter disorders.

Results

Between May 1997 and November 2014 the PIND study identified 349 children with diagnosed leukodystrophies, giving an estimated UK lifetime risk of 31/million live births. There were 18 specific diseases in the group and relatively large numbers of affected children came from consanguineous Pakistani families. In addition there were 454 children with genetic leukoencephalopathies – in this group there were 38 diseases. 5.8% of children with scan evidence of brain white matter disorders did not receive a specific diagnosis.

Interpretation

These unique prospectively‐obtained national data avoid the selection bias inherent in reports from single centres. White matter disorders of the central nervous system comprise more than half of UK paediatric neurodegenerative diseases meeting the PIND criteria. This paper reports the lifetime risk/million live births for the commonest leukodystrophies, providing a basis for comparison with future studies.
Comparison of alogliptin and glipizide for composite endpoint of glycated haemoglobin reduction, no hypoglycaemia and no weight gain in type 2 diabetes mellitus
Authors: Del Prato S. , Fleck P. , Wilson C. , Chaudhari P.
Published: February 2016

This was a post hoc analysis of a 2‐year, double‐blind study of 2639 patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin monotherapy, which assessed achievement of a composite endpoint of sustained glycated haemoglobin (HbA1c) reduction (≤7.0% at week 104 or ≥0.5% decrease from baseline) with no weight gain and no hypoglycaemic events with alogliptin 12.5 and 25 mg daily or glipizide (≤20 mg daily), each added to metformin. With an HbA1c target of ≤7.0%, 24.2 and 26.9% of patients treated with alogliptin 12.5 and 25 mg, respectively, achieved the composite endpoint versus 10.7% of patients treated with glipizide (both p < 0.001). With a criterion of ≥0.5% decrease in HbA1c, the composite endpoint was reached in 22.5, 25.2 and 10.4% of patients treated with alogliptin 12.5 mg, alogliptin 25 mg and glipizide, respectively. Odds ratios for achieving the composite endpoint favoured alogliptin in the primary analysis set and in all subgroups of patients. Patients with T2DM failing metformin monotherapy were more likely to achieve sustained glycaemic control with no hypoglycaemia or weight gain at 2 years with alogliptin than with glipizide.
L‐arginine promotes gut hormone release and reduces food intake in rodents
Authors: Alamshah A. , McGavigan A. K. , Spreckley E. , Kinsey‐Jones J. S. , Amin A. , Tough I. R. , O'Hara H. C. , Moolla A. , Banks K. , France R. , Hyberg G. , Norton M. , Cheong W. , Lehmann A. , Bloom S. R. , Cox H. M. , Murphy K. G.
Published: February 2016

Aims

To investigate the anorectic effect of L‐arginine (L‐Arg) in rodents.

Methods

We investigated the effects of L‐Arg on food intake, and the role of the anorectic gut hormones glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY), the G‐protein‐coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents.

Results

Oral gavage of L‐Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet‐induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L‐Arg stimulated GLP‐1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP‐1 and PYY receptors did not influence the anorectic effect of L‐Arg. L‐Arg‐mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L‐Arg suppressed food intake in rats.

Conclusions

L‐Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L‐Arg is unlikely to be mediated by GLP‐1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L‐Arg suppressed food intake in rats, suggesting that L‐Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L‐Arg suppresses food intake and its utility in the treatment of obesity.
Ictal motor sequences: Lateralization and localization values
Authors: Marashly Ahmad , Ewida Amr , Agarwal Rajkumar , Younes Kyan , Lüders Hans O.
Published: February 2016

Objective

To determine the lateralization and localization values of ictal motor sequences in the setting of focal epilepsy ending with a secondarily generalized motor seizure.

Methods

Retrospectively, the ictal motor sequences were analyzed in patients with focal epilepsy ending with a secondarily generalized motor seizure by three readers blinded to all clinical and electrographic data. One representative seizure per patient was selected. Prevalence, positive predictive value (PPV), and Fleiss Kappa for the following motor signs were calculated: version, unilateral limb tonic posturing, unilateral limb clonic seizure, figure‐of‐4, M2e, hand dystonia, clonic asymmetric ending, and Todd's paralysis. Sequences of signs with a PPV ≥ 80% were then analyzed to determine their lateralization and localization values.

Results

A total of 47 seizures were studied. The “reliable” motor signs with a robust lateralizing value (PPV > 80%) were version, unilateral tonic posturing, M2e, unilateral clonic seizure, asymmetric clonic ending, and Todd's paralysis. Figure‐of‐4 and hand dystonia had a relatively low PPV, and therefore were not included in the following sequence analysis, which included only 38 patients with two or more motor signs of high PPV. Multiple combinations of temporal progression of motor signs were seen in these 38 patients, with version being the most common initial motor sign (29 of 38 patients) usually followed by M2e (15 of 29 patients), and/or a focal tonic seizure (7 of 29 patients). Accurate lateralization of the epileptogenic zone (EZ) with a PPV of 100% can be predicted when two or more reliable motor signs point to the same side. However, the various sequences of reliable motor signs did not differentiate between temporal and extratemporal epilepsy.

Significance

The presence of reliable ictal motor signs in focal epilepsy is extremely valuable in lateralizing the EZ, but not in determining the localization of the EZ. This is especially useful when epilepsy surgery is indicated.