bluuebunny/crossref_metadata_2025 huggingface dataset:
novoCaller: a Bayesian network approach for de novo variant calling from pedigree and population sequence data
Authors: Mohanty Anwoy Kumar , Vuzman Dana , Francioli Laurent , Cassa Christopher ,   Brigham Genomic Medicine,   Undiagnosed Diseases Network,   Brigham and Women’s Hospital FaceBase Project, Toth-Petroczy Agnes , Sunyaev Shamil
Published: August 2018

Motivation

De novo mutations (i.e. newly occurring mutations) are a pre-dominant cause of sporadic dominant monogenic diseases and play a significant role in the genetics of complex disorders. De novo mutation studies also inform population genetics models and shed light on the biology of DNA replication and repair. Despite the broad interest, there is room for improvement with regard to the accuracy of de novo mutation calling.

Results

We designed novoCaller, a Bayesian variant calling algorithm that uses information from read-level data both in the pedigree and in unrelated samples. The method was extensively tested using large trio-sequencing studies, and it consistently achieved over 97% sensitivity. We applied the algorithm to 48 trio cases of suspected rare Mendelian disorders as part of the Brigham Genomic Medicine gene discovery initiative. Its application resulted in a significant reduction in the resources required for manual inspection and experimental validation of the calls. Three de novo variants were found in known genes associated with rare disorders, leading to rapid genetic diagnosis of the probands. Another 14 variants were found in genes that are likely to explain the phenotype, and could lead to novel disease-gene discovery.

Availability and implementation

Source code implemented in C++ and Python can be downloaded from https://github.com/bgm-cwg/novoCaller.

Supplementary information

Supplementary data are available at Bioinformatics online.
Can Immune Checkpoint Inhibitors Induce Microscopic Colitis or a Brand New Entity?
Authors: Choi Kati , Abu-Sbeih Hamzah , Samdani Rashmi , Nogueras Gonzalez Graciela , Raju Gottumukkala Subba , Richards David M , Gao Jianjun , Subudhi Sumit , Stroehlein John , Wang Yinghong
Published: August 2018

Background

Microscopic colitis (MC) has been described as 1 pattern of injury in immune checkpoint inhibitor (ICPI)–induced colitis. The main objective of this study was to characterize ICPI-induced MC by exploring the differences in risk factors, colitis treatments, endoscopic features, and clinical outcomes between cancer and noncancer patients with MC with and without exposure to ICPIs.

Methods

A retrospective chart review was conducted among patients diagnosed with MC from our institutional pathology database from January 2012 to January 2018. Patients were categorized into MC in cancer patients with or without ICPI exposure and in noncancer patients. Risk factors (use of tobacco and certain medications), colitis treatments (antidiarrheals and immunosuppressants), endoscopic features (with or without mucosal abnormality), and clinical outcomes (diarrhea recurrence, hospitalization, mortality) were collected and compared among the 3 groups.

Results

Of the 65 eligible patients with MC, 15 cancer patients had exposure to ICPI, 39 cancer patients had no exposure to ICPI, and 11 had no cancer diagnosis. Among the risk factors, proton pump inhibitor was more frequently used in the ICPI-induced MC cohort (P = 0.040). Furthermore, in this population, mucosal abnormality was the most common endoscopic feature compared with normal findings in the non-ICPI-induced MC groups (P = 0.106). Patients with ICPI-induced MC required more treatments with oral and intravenous steroids and nonsteroidal immunosuppressive agents (all P < 0.001) and had a higher rate of hospitalization (P < 0.001).

Conclusion

This study suggests that despite some similarities between MC with and without exposure to ICPIs, ICPI-induced MC has a more aggressive disease course that requires more potent immunosuppressive treatment regimens and greater need for hospitalization.
Harms at the Crossroads of Carework and Irregular Migration
Authors: Cochrane Brandy
Published: August 2018

Refugee and asylum-seeking mothers perform the duties of carework during and after the complex circumstances associated with irregular journeys and settlement in host countries. Utilizing motherhood as a central frame, the article links policies of border securitization with the tangible gendered consequences they produce in the daily carework of mothers. Past literature has explored gendered implications of border crossings and settlement, but rarely have authors examined these themes in tandem and never in the context of mothers and their carework. Based on narrative interviews with refugee and asylum-seeking mothers, I analyse how mothers’ everyday lives and, more specifically, their performance of carework are disrupted during migration, by boat journeys and detention, and after migration, by limited governmental assistance and restricted family reunification in host countries.
Measures of Feigned or Exaggerated Incompetence
Authors: Rubenzer Steve
Published: August 2018

This chapter describes and reviews the published instruments available to assess feigned incompetence to stand trial. The Inventory of Legal Knowledge has already gained considerable acceptance despite having some significant limitations. The ECST-R Atypical Presentation Scales are included as part of the ECST-R competency assessment instrument and are billed as screening tests for feigned incompetence. However, they address only feigned psychopathology, not feigned cognitive impairment or ignorance of the court system, and are billed as suitable only for screening, not diagnostic, purposes. The strengths and weaknesses of the ILK and the ECST-R are discussed in detail, as are emerging instruments and detection strategies.
Report Writing and Testimony
Authors: Rubenzer Steve
Published: August 2018

This chapter examines the purposes of a forensic report and the choices an author faces regarding a report’s structure, content, and tone. The chapter presents suggestions for steps an examiner can take during the information-gathering stage that will benefit the assessment and make report writing more efficient. Prior recommendations for forensic reports in general are reviewed, including means for proactively addressing possible bias. Suggestions for new formats and innovation are advanced, as is a checklist of desirable CST report attributes. The chapter also presents recommendations for testimony, which, in turn, have implications for report length and format. The research on effective testimony is briefly reviewed, and helpful tips are offered.
Clustering of behavioural risk factors for health in UK adults in 2016: a cross-sectional survey
Authors: Birch Jack , Petty Robert , Hooper Lucie , Bauld Linda , Rosenberg Gillian , Vohra Jyotsna
Published: August 2018

Background

Foods high in fat, sugar and salt (HFSS) are known to contribute to overweight and obesity. In addition to overweight and obesity, smoking, alcohol consumption and physical inactivity are known risk factors for non-communicable diseases, including several cancers and cardiovascular disease.

Methods

Secondary analysis of UK-representative cross-sectional survey data of 3293 adults aged 18+. Regression analyses were undertaken to understand the relationship between consumption of HFSS food and soft drinks, alcohol and tobacco and socio-demographics. Clustering analysis identified groupings of health risk factors.

Results

Males, those aged 18–24 and those from the more deprived groups consumed ready meals and fast food most frequently. Most of the sample (77.3%) engaged in at least one health risk behaviour. Six clusters were identified in the clustering analysis. Older (65+) female respondents were more likely to be inactive. Smokers exhibiting additional risk behaviours were more likely to be of working age from more deprived groups, and men over 65 were more likely to consume harmful levels of alcohol with additional risk factors.

Conclusion

Policies and services in the UK tend to focus on changing behaviour to address individual risk factors. This study shows that policies and interventions need to address multiple risk factors.
An extension of orthogonality relations based on norm derivatives
Authors: Zamani Ali , Moslehian Mohammad Sal
Published: August 2018

We introduce the relation ρλ-orthogonality in the setting of normed spaces as an extension of some orthogonality relations based on norm derivatives and present some of its essential properties. Among other things, we give a characterization of inner product spaces via the functional ρλ. Moreover, we consider a class of linear mappings preserving this new kind of orthogonality. In particular, we show that a linear mapping preserving ρλ-orthogonality has to be a similarity, that is, a scalar multiple of an isometry.
Social Norms and Household Savings Rates in China
Authors: Chen Yvonne Jie , Chen Zhiwu , He Shijun
Published: August 2018

We study the effects of Confucian social norms on savings rates in China. In our simple two-period model, parents have the option to invest in either a risk-free asset or their children’s human capital. We assume that the filial piety norms and thus the enforcement mechanisms for supporting old-age parents differ across regions. Consequently, the probability of children’s non-performance of their repayment obligations to parents and the returns parents can expect from investing in their children vary. We test the model predictions using data from the China Household Finance Survey. We find that stronger Confucian social norms reduce the gap in the savings rate between families with sons and with daughters. Modeling default by children as a function of the prevailing social norms gives us the flexibility to study the impacts of declining Confucian influence on consumption–savings trends in China.
RETROSPECTIVE ANALYSIS OF PATIENT RADIATION DOSES IN DIGITAL CORONARY ANGIOGRAPHY AND INTERVENTIONS
Authors: Al-Jabri Amna J , Alzimami Khalid , Alsafi K , Alaamer Abdulaziz S , Al-Rajhi M A , Suliman I I
Published: August 2018

This study sought to assess patient and operator eye lens doses in diagnostic coronary angiography (DCA) and percutaneous coronary interventions (PCI) in a University hospital in Oman. Kerma area product (PkA), cumulative air kerma (CAK) and fluoroscopic time (FT) were retrospectively recorded from the DICOM header for 264 patients. The median (interquartile range) of FT, PKA and CAK were: 5.3 min (2.6–10.5), 60.9 Gy cm2 (41.3–91.4) and 0.86 Gy (0.61–1.29), respectively, for DCA procedures, and they were 20.2 min (13.3–30.1), 174.0 Gy cm2 (113.7–253.3) and 2.6 Gy (1.8–3.9), respectively, for PCI procedures. The results revealed wide variability in patient doses among individual patients. Monitoring and recording patient dose data can be valuable for quality assurance and patient safety purposes. Feedback to the operator may help optimize radiation doses to patients and prompt further action, as needed.
Medicago sativa has Reduced Biomass and Nodulation When Grown with Soil Microbiomes Conditioned to High Phosphorus Inputs
Authors: Kaminsky Laura M. , Thompson Grant L. , Trexler Ryan V. , Bell Terrence H. , Kao-Kniffin Jenny
Published: August 2018

Agricultural over-fertilization may adversely impact plant−microbial interactions affecting crop yield. It is unclear if soil microbiomes respond quickly to changes in fertilizer inputs once conditioned to specific nutrient regimes. We conducted a growth chamber study assessing the compositional and functional resilience of root-associated microbiomes of Medicago sativa to nutrient regime changes, and consequences for plant growth. Plants were grown with a common starting soil microbiome under four nutrient treatments: control (no fertilizer), organic phosphorus (compost added), low inorganic P (low triple superphosphate, TSP) and high inorganic P (high TSP). After several conditioning generations, in which microbiomes from rhizospheres of high biomass plants were transferred forward, microbiome composition was distinct across the four treatments. The resulting microbiomes were then transplanted into each of the nutrient treatments, leading generally to functional changes in hydrolytic enzyme activity and taxonomic convergence with other microbiomes transplanted into the same nutrient regime. However, high inorganic P-conditioned microbiomes were resistant to compositional change. Correspondingly, M. sativa grown with high inorganic P-conditioned microbiomes had lower biomass, fewer nodules, and lower %N than plants grown under the same nutrient regime with other microbiomes. These findings suggest that excessive inorganic P fertilization may change microbiomes such that they negatively affect plant growth.
MPB, a novel berberine derivative, enhances lysosomal and bactericidal properties via TGF‐β–activated kinase 1‐dependent activation of the transcription factor EB
Authors: Liu Xiaojia , Zhang Na , Liu Yang , Liu Lu , Zeng Qingxuan , Yin Mingxiao , Wang Yanxiang , Song Danqing , Deng Hongbin
Published: August 2018

Lysosome has a crucial role in clearance of endocytosed pathogens from the cell. Small molecules that can boost lysosome function and bactericidal ability to cope with subsequent infection are urgently needed. Here, we report that MPB, a novel berberine derivative, induced lysosome‐based degradation and clearance of methicillin‐resistant Staphylococcus aureus and enteroinvasive Escherichia coli in macrophages. MPB caused nuclear translocation of transcription factor EB (TFEB), which boosted expression of lysosome genes. TFEB silencing repressed the MPB‐mediated enhancements in degradation and bacterial eradication. MPB switched on TFEB nuclear translocation by coupling 2 parallel signaling pathways. MPB‐triggered JNK activation led to 14‐3‐3δ being released from TFEB, which, in turn, caused TFEB nuclear translocation. In addition, MPB induced AMPK activation and subsequent inhibition of mechanistic target of rapamycin activity, which also contributed to TFEB nuclear translocation. Importantly, genetical or pharmaceutical inhibition of TGF‐β–activated kinase 1 (TAK1) reduced MPB action remarkably. MPB acted through TAK1 at lysine 158 to activate JNK and AMPK and, thus, induced TFEB‐dependent bactericidal activity in macrophages. Therefore, our study reveals a novel mechanism by which MPB controls JNK and AMPK phosphorylation cascades to activate lysosomal function and bactericidal activity via TAK1 K158–dependent manner, which may offer insight into novel therapeutic strategies to control bacterial infection.—Liu, X., Zhang, N., Liu, Y., Liu, L., Zeng, Q., Yin, M., Wang, Y., Song, D., Deng, H. MPB, a novel berberine derivative, enhances lysosomal and bactericidal properties via TGF‐β–activated kinase 1‐dependent activation of the transcription factor EB. FASEB J. 33, 1468–1481 (2019). www.fasebj.org
Intervention Descriptions in Medical Education: What Can Be Improved? A Systematic Review and Checklist
Authors: Meinema Jennita G. , Buwalda Nienke , van Etten-Jamaludin Faridi S. , Visser Mechteld R.M. , van Dijk Nynke
Published: August 2018

Purpose

Many medical education studies focus on the effectiveness of educational interventions. However, these studies often lack clear, thorough descriptions of interventions that would make the interventions replicable. This systematic review aimed to identify gaps and limitations in the descriptions of educational interventions, using a comprehensive checklist.

Method

Based on the literature, the authors developed a checklist of 17 criteria for thorough descriptions of educational interventions in medical education. They searched the Ovid MEDLINE, Embase, and ERIC databases for eligible English-language studies published January 2014–March 2016 that evaluated the effects of educational interventions during classroom teaching in postgraduate medical education. Subsequently, they used this checklist to systematically review the included studies. Descriptions were scored 0 (no information), 1 (unclear/partial information), or 2 (detailed description) for each of the 16 scorable criteria (possible range 0–32).

Results

Among the 105 included studies, the criteria most frequently reported in detail were learning needs (78.1%), content/subject (77.1%), and educational strategies (79.0%). The criteria least frequently reported in detail were incentives (9.5%), environment (5.7%), and planned and unplanned changes (12.4%). No article described all criteria. The mean score was 15.9 (SD 4.1), with a range from 8 (5 studies) to 25 (1 study). The majority (76.2%) of articles scored 11–20.

Conclusions

Descriptions were frequently missing key information and lacked uniformity. The results suggest a need for a common standard. The authors encourage others to validate, complement, and use their checklist, which could lead to more complete, comparable, and replicable descriptions of educational interventions.
You Belong in the Room: Addressing the Underrepresentation of Physicians With Physical Disabilities
Authors: Schwarz Charlotte M. , Zetkulic Marygrace
Published: August 2018

In this Invited Commentary, the authors use personal experiences to highlight how obstacles for qualified candidates with physical disabilities persist in medical education, especially at entry to and early stages of training. In an era when medical schools and residency programs advocate principles of diversity and inclusion, it is estimated that medical students with physical disabilities still comprise less than 1% of learners. The authors present four constructive actions to address the underrepresentation of individuals with physical disabilities in medical schools: (1) acknowledging biases, (2) building networks, (3) reassessing the undifferentiated model of medical education, and (4) advocating the advantages of physicians with disabilities. Supporting trainees and practicing physicians with physical disabilities requires pragmatic evaluation of the essential functions of contemporary medical education, as well as lateral thinking to approach clinical work in innovative ways.
Prothrombin Complex Concentrates for Perioperative Vitamin K Antagonist and Non–vitamin K Anticoagulant Reversal
Authors: Levy Jerrold H. , Douketis James , Steiner Thorsten , Goldstein Joshua N. , Milling Truman J.
Published: August 2018

Vitamin K antagonist therapy is associated with an increased bleeding risk, and clinicians often reverse anticoagulation in patients who require emergency surgical procedures. Current guidelines for rapid anticoagulation reversal for emergency surgery recommend four-factor prothrombin complex concentrate and vitamin K coadministration. The authors reviewed the current evidence on prothrombin complex concentrate treatment for vitamin K antagonist reversal in the perioperative setting, focusing on comparative studies and in the context of intracranial hemorrhage and cardiac surgery. The authors searched Cochrane Library and PubMed between January 2008 and December 2017 and retrieved 423 English-language papers, which they then screened for relevance to the perioperative setting; they identified 36 papers to include in this review. Prothrombin complex concentrate therapy was consistently shown to reduce international normalized ratio rapidly and control bleeding effectively. In comparative studies with plasma, prothrombin complex concentrate use was associated with a greater proportion of patients achieving target international normalized ratios rapidly, with improved hemostasis. No differences in thromboembolic event rates were seen between prothrombin complex concentrate and plasma, with prothrombin complex concentrate also demonstrating a lower risk of fluid overload events. Overall, the studies the authors reviewed support current recommendations favoring prothrombin complex concentrate therapy in patients requiring vitamin K antagonist reversal before emergency surgery.
Hearing Protector Attenuation and Noise Exposure Among Metal Manufacturing Workers
Authors: Sayler Stephanie K. , Rabinowitz Peter M. , Galusha Deron , Sun Kan , Neitzel Richard L.
Published: August 2018

Objectives:

This study utilized personal noise measurements and fit-testing to evaluate the association between noise exposures and personal attenuation rating (PAR) values among participating workers, and second, to compare the attenuated exposure levels received by the workers and the British Standards Institute’s recommended noise exposure range of 70 to 80 dBA.

Design:

We measured hearing protection device (HPD) attenuation among a sample of 91 workers at 2 US metal manufacturing facilities, through performance of personal noise dosimetry measurements and HPD fit-testing over multiple work shifts. We compared this testing with participant questionnaires and annual audiometric hearing threshold results.

Results:

The average 8-hr time-weighted average noise exposures for study participants was 79.8 dBA (SD = 7.0 dBA), and the average PAR from fit-testing was 20.1 dB (±6.7 dB). While differences existed between sites, 84% of the 251 PAR measurements resulted in effective protection levels below the recommended 70 dBA (indicating overprotection), while workers were underprotected (i.e., effective exposures >80 dBA) during <1% of monitored shifts. Our results also demonstrated a significant positive relationship between measured noise exposure and PAR among non–custom-molded plug users (p = 0.04). Non–custom-molded plug wearers also showed a significant increase in PAR by sequential fit-test interaction (p = 0.01), where on average, subsequent fit-testing resulted in increasingly higher HPD attenuation. Workers at site 1 showed higher PARs. PARs were significantly related to race, even when adjusting for site location. While age, hearing threshold level, task, and self-reported tinnitus showed no significant effect on individual PAR in an unadjusted model, site, race, and sand- or water-blasting activities were significant predictors in adjusted models. Within-worker variability in time-weighted averages and PARs across repeated measurements was substantially lower than variability between workers.

Conclusions:

Careful selection of HPDs is necessary to minimize instances of overprotection to workers in low and moderate occupational noise environments. The use of fit-testing in hearing conservation programs to evaluate PAR is recommended to avoid overprotection from noise exposure while also minimizing instances of under-attenuation.
Effectiveness of Interventions Teaching Cross-Cultural Competencies to Health-Related Professionals With Work Experience: A Systematic Review
Authors: Filmer Tobias , Herbig Britta
Published: August 2018

Introduction:

Because of the increasing diversity in society, health professionals are working with patients from many different cultural backgrounds. Interventions to improve culture-specific competencies in health care have been shown to be successful. However, there is an increasing demand for continuing professional development in general cross-cultural competencies that do not focus on specific cultures. Previous reviews do not differentiate between general cross-cultural and culturally specific competencies. This review assesses the effectiveness of interventions that aim to increase cross-cultural competencies in health professionals.

Methods:

Databases were searched systematically to identify quantitative and qualitative studies that focus on cross-cultural competencies in health care professions. Two independent raters used an assessment tool (Quality Assessment Tool for Studies with Diverse Designs, QATSDD) to rate the quality of the results.

Results:

Thirty-one of 34 identified studies described cross-cultural competency interventions to be effective in terms of participants' satisfaction with the interventions and self-rated knowledge improvement. Nineteen studies relied exclusively on subjective assessment methods. Most of them reported significant findings, whereas results from five studies with independent ratings or objective assessments were mostly not significant. Many studies lacked in providing sufficient data on intervention descriptions.

Discussion:

Cross-cultural competency interventions seem to be effective—according to self-ratings by participants. However, the definitions of cultural competency, the objectiveness of measurements, and the types of study outcomes were varied. To evaluate the success of cross-cultural competency interventions, more evidence from objective, behavioral assessments is needed. Studies should investigate the differential impact of various intervention types and need to provide detailed reporting on methods and outcomes.
Professional Identity Formation in HIV Care: Development of Clinician Scholars in a Longitudinal, Mentored Training Program
Authors: Carlberg-Racich Suzanne , Wagner Cornelia M. J. , Alabduljabbar Salma A. , Rivero Ricardo , Hasnain Memoona , Sherer Renslow , Linsk Nathan L.
Published: August 2018

Introduction:

The Clinician Scholars Program is designed to improve the capacity and quality of HIV care by training clinicians in underserved areas. A mentoring approach is used to deliver individualized educational opportunities over the course of a year focused on preparing clinicians to provide high-quality patient-centered HIV care. Evaluation of the program has illustrated increases in knowledge, skills, and practice behavior, yet critical domains remain unexplored, particularly the potential for the program to affect professional identity formation and networking between individual clinicians.

Methods:

Qualitative exit interviews (N = 50) were conducted over 4 years of the Clinician Scholars Program. Interviews were transcribed and analyzed using an open-coding process with multiple coders. Interrater reliability was assessed. Themes related to professional development and networking emerged.

Results:

Thematic analysis revealed changes in several professional development domains, including self-efficacy, HIV care clinician identity, and career development. In addition, clinicians began to develop key connections with mentors, other clinicians, and health systems—gaining a foundation in the HIV care community, enabled and strengthened by growth in professional confidence and competence within the clinician's care context.

Discussion:

Evaluations of clinical training programs often focus on knowledge and skill gains without addressing professional identity development and place within the care community. This study illustrates that a longitudinal clinician training program has the potential to influence professional identify development, particularly affect how clinicians view themselves as a resource in the HIV care community and begins to facilitate necessary connections to other clinicians and the wider care system.
Developing an Innovative Statewide Infrastructure and Model for Delivering Continuing Interprofessional Education: The North Carolina AHEC Initiative
Authors: Rogers Russet R. , Owen John A. , Lake Donna M. , Durham Carol Fowler , Latham Tina G. , Sherwood Gwen , Golding Christopher S.
Published: August 2018

Introduction:

North Carolina AHEC (NC AHEC) leadership recognized that continuing interprofessional education (CIPE) is vital for improving patient care and outcomes. Rather than train and educate in professional silos, interprofessional education presented an opportunity to reframe continuing education (CE) to improve the integration of care delivery and outcomes.

Methods:

In April 2014, two regional AHECs collaborated to design a statewide initiative for AHEC CE leaders, CE professionals, and CE faculty to learn about integrating interprofessional education into CE planning and implementation. The design of this innovative initiative develops a common knowledge base in CIPE, promotes collaboration, avoids duplication, and creates shared definitions and standards to advance CIPE across the NC AHEC program.

Results:

The NC AHEC CIPE Initiative drew participation from CE leaders, CE professionals, and CE faculty. Immediately after the completion of the Initiative, seven AHECs completed CIPE events. By June 2017, AHECs across the state had offered a total of 36 CIPE events.

Discussion:

The NC AHEC CIPE Initiative demonstrates that it is possible to implement CIPE programming in a regional CE context. The education model promoted changes in knowledge, competence, and performance of CE professionals and faculty. Critical success factors include leadership support, functioning as a community of practice, engaging experts to train CE professionals and faculty, and using technology to span geographic distance of learners.
Chronic clozapine treatment improves the alterations of prepulse inhibition and BDNF mRNA expression in the medial prefrontal cortex that are induced by adolescent social isolation
Authors: Li Man , Wang Weiwen , Sun Lan , Du Wei , Zhou Hao , Shao Feng
Published: August 2018

Isolation rearing produces significant behavioral and neurochemical dysfunctions in rodents, which resemble the symptoms of schizophrenia. Clozapine, one of the atypical antipsychotics, is widely used in the treatment of schizophrenia patients and in experimental studies. In this study, male Sprague Dawley rats were randomly assigned to either group-reared or isolation-reared conditions during postnatal days (PNDs) 21–34. During PNDs 46–55, the rats were subjected to chronic clozapine (1.0 mg/kg for 10 days) or saline treatment. On PND 56, all rats underwent behavioral testing and then were sacrificed for biochemical testing. The results indicated that adolescent social isolation induced impairments in prepulse inhibition and reversal learning, and clozapine injection improved the prepulse inhibition disruption but not reversal learning ability. Furthermore, clozapine administration reversed the increased brain-derived neurotrophic factor (BDNF) mRNA level in the medial prefrontal cortex (mPFC) that was induced by adolescent isolation. However, clozapine decreased the BDNF mRNA level in the mPFC in group-reared rats. Together, our findings provide additional evidence that a low dose of chronic clozapine treatment could improve information filtering/sensorimotor gating and alterations in the BDNF mRNA level in the mPFC induced by adolescent social isolation.
Correlation Between Visual Function and Performance of Simulated Daily Living Activities in Glaucomatous Patients
Authors: Lombardi Marco , Zenouda Ariel , Azoulay-sebban Line , Lebrisse Marie , Gutman Emmanuel , Brasnu Emmanuelle , Hamard Pascale , Sahel José-Alain , Baudouin Christophe , Labbé Antoine
Published: August 2018

Purpose:

To analyze the correlations between functional clinical tests and the performance of glaucoma patients in simulated daily living activities.

Patients and Methods:

Thirty-two patients with chronic glaucoma, followed at the Quinze-Vingts National Ophthalmology Hospital, were included. All patients had a clinical evaluation of visual function including best-corrected visual acuity, contrast sensitivity, and monocular and binocular visual field (VF) tests. Four different simulated activities of daily living were evaluated in standardized artificial platforms (StreetLab and HomeLab): “mobility” and an obstacle avoidance task in an artificial street, “reaching and grasping” large and small objects on a kitchen work surface, “localization of people” and “face orientation recognition.” Patient performance in the different tasks was correlated with VF evaluation including integrated binocular visual field (IVF), VF mean deviation (MD) of the better and the worse eye, Esterman binocular VF, best-corrected visual acuity, and contrast sensitivity.

Results:

The IVF score was significantly correlated with “localization of people” time (r=0.49; P=0.003), “face orientation recognition” time (r=0.50; P=0.002), and “movement onset” for reaching and grasping small objects (r=0.38; P=0.029). The MD of the better eye appeared significantly correlated with “face orientation recognition” time (r=−0.44; P=0.009) and “localization of people” time (r=−0.46; P=0.005). The Esterman score appeared significantly correlated with “mobility time” (r=−0.40; P=0.018), “localization of people” (r=−0.37; P=0.030), “face orientation recognition” times (r=−0.39; P=0.024), and “movement onset” for reaching and grasping large objects (r=−0.43; P=0.015).

Conclusions:

The IVF score and the MD of the better eye appeared to better evaluate “reaching and grasping,” “face orientation recognition,” and “localization of people” simulated tasks, whereas for the “mobility” task, the Esterman VF seemed more useful. The precise evaluation of the glaucoma patient’s ability to perform everyday life tasks is complex and may require both monocular and binocular VF tests.
Relationships Between Specific Functional Abilities and Health-Related Quality of Life in Chronic Traumatic Spinal Cord Injury
Authors: Goulet Julien , Richard-Denis Andréane , Thompson Cynthia , Mac-Thiong Jean-Marc
Published: August 2018

Objective

The objective of this study was to explore the relationships between specific functional abilities assessed from the third version of the Spinal Cord Injury Measure and health-related quality of life after a traumatic spinal cord injury.

Design

A prospective cohort of 195 patients who had sustained a traumatic spinal cord injury from C1 to L1 and consecutively admitted to a single level 1 spinal cord injury–specialized trauma center between April 2010 and September 2016 was studied. Correlation coefficients were calculated between Spinal Cord Injury Measure scores and Short Form 36 version 2 summary scores (physical component score; mental component score).

Results

The total Spinal Cord Injury Measure score correlated moderately with the physical component score in the entire cohort, correlated strongly with physical component score in tetraplegics, did not correlate with physical component score in paraplegics, and did not correlate with mental component score. Mobility subgroup and individual items scores showed the strongest correlations with the physical component score in the entire cohort, followed by self-care and sphincter management.

Conclusions

This work is significant being the first to determine which specific functional abilities are mostly related to health-related quality of life and highlights the differences between tetraplegic and paraplegic patients. Our findings could help clinicians to guide rehabilitation plan based on importance of specific functional abilities in relationship with the health-related quality of life.
Cost-Effectiveness Analysis of Demineralized Bone Matrix and rhBMP-2 versus Autologous Iliac Crest Bone Grafting in Alveolar Cleft Patients
Authors: Mehta Sagar , Blagg Ross , Willcockson James , Gociman Barbu , Yamashiro Duane , Siddiqi Faizi
Published: August 2018

Background:

The standard of care for patients with alveolar cleft deformities is autologous bone grafting using iliac crest bone graft (ICBG). The combination of demineralized bone matrix with recombinant human bone morphogenetic protein-2 (DBX/rhBMP-2), as a substitute for ICGB, has been shown to have similar bony incorporation within the maxilla without donor-site morbidity. It has been argued that one of the drawbacks of using DBX/rhBMP-2 is the higher cost. The aim of this study was to compare the cost, operative time, and hospital length of stay associated with these two treatment modalities.

Methods:

A chart review was conducted for 71 patients who underwent secondary alveolar cleft reconstruction. Forty patients received ICBG and 31 patients underwent reconstruction using DBX/rhBMP-2. Operative costs, operative time, and hospital length of stay were compared between the two groups.

Results:

The average total operative cost was $6892 in the ICBG surgery population versus $4836 in the DBX/rhBMP-2 population (p < 0.01). Statistically significant decreases in anesthesia, pharmacy, and operating room costs were found in patients who underwent the DBX/rhBMP-2 surgery. Operative time decreased from an average of 97.3 minutes to 67.0 minutes (p < 0.01), and length of inpatient stay decreased from an average of 29.8 hours to 9.3 hours (p < 0.01).

Conclusion:

In the treatment of alveolar cleft deformities, operative material costs were greater in the DBX/rhBMP-2 group but—secondary to decreased hospital, anesthesia, pharmacy, and operating room costs—DBX/rhBMP-2 was more cost-effective than ICBG.
Abandoning the Supraorbital Bandeau in Anterior Craniosynostosis Repairs, for a Single-Segment Reconstruction
Authors: Fearon Jeffrey A. , Ditthakasem Kanlaya , Garcia Jose Castro , Herbert Morley
Published: August 2018

Background:

Following correction of anterior sutural fusions, long-term forehead irregularities may arise. Based on the premise that frontal reconstructions using a seamless construct might produce better long-term aesthetic results, the supraorbital bandeau was abandoned for a single-piece frontal reconstruction. The purpose of this review was to compare outcomes and complications between children who underwent reconstruction with the traditional supraorbital bandeau and those who underwent reconstruction with a single bony segment.

Methods:

A retrospective sequential chart review was performed of all children undergoing anterior sutural fusion repairs to compare supraorbital bandeau to single-segment reconstructions. Length of surgery, blood loss, hospital stay, and complications were assessed. Aesthetic outcomes and reoperation rates were also examined.

Results:

Over 10 years, 199 patients with anterior sutural fusions underwent correction: 124 with a single-piece frontal reconstruction and 75 with traditional supraorbital bandeaus. Outcome analyses revealed no significant differences between techniques with respect to blood loss, surgical times, complication rates, and hospital length of stay. A preliminary analysis suggested lower reoperation rates (0 percent versus 2.7 percent) and more favorable aesthetic rankings for those treated with a single segment, although the follow-up for this group was significantly shorter compared with those treated with a supraorbital bandeau (16 months versus 43 months).

Conclusions:

Abandoning the traditional supraorbital bandeau for a simplified single-segment frontal reconstruction has the potential to result in improved forehead aesthetics, although longer term evaluations are needed. This review suggests that this technical variation does not appear to be associated with longer surgical times, increased blood loss, or higher complication rates.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Ankle Arthrodesis with Free Vascularized Fibula Autograft Using Saphenous Vein Grafts: A Case Series
Authors: Piccolo Paulo P. , Ben-Amotz Oded , Ashley Blair , Wapner Keith L. , Levin L. Scott
Published: August 2018

Background:

In select high-risk cases of ankle arthrodesis, conventional techniques may lead to a high incidence of failure because of a combination of multiple operations; high risk of infection; avascular, often bulky allografts; and poor soft-tissue quality. In high-risk distal limb salvage, the authors have performed ankle arthrodesis using a free vascularized fibula graft from the ipsilateral limb with saphenous vein grafts.

Methods:

The authors present data from six patients. The cause of the defect was avascular necrosis of the talus (n = 4), osteomyelitis (n = 1), and failed total ankle replacement (n = 1). The ipsilateral fibula was used in all cases as a free vascularized graft. Nonviable bone and soft tissue were débrided, and the fibula was shortened to size and impacted into the cavitary space spanning the distance between the tibia, talus, and calcaneus. The pedicle distally was anastomosed to saphenous vein grafts and proximally anastomosed to the divided peroneal vessels.

Results:

The flap success rate was 83 percent (n = 5). The complication rate was 83 percent; complications included flap loss (intraoperative arterial thrombosis), loss of skin island, hematoma, and arterial thrombosis. Despite one flap failure and a high complication rate, successful union was obtained in all patients. All patients achieved full weight-bearing status by a mean of 4 months after surgery (range, 3 to 7 months). There were no amputations.

Conclusions:

Vascularized free fibula graft is a reliable option for ankle arthrodesis in complex salvage situations. Using a saphenous vein graft to perform the anastomosis with the divided peroneal vessels proximally should be considered.
Outcomes following Autologous Fat Grafting for Oncologic Head and Neck Reconstruction
Authors: Karmali Riaz J. , Hanson Summer E. , Nguyen Alexander T. , Skoracki Roman J. , Hanasono Matthew M.
Published: August 2018

Background:

The aims of this study were to examine the surgical, oncologic, and aesthetic outcomes of patients undergoing autologous fat grafting for oncologic head and neck reconstruction.

Methods:

A review was performed of 119 consecutive patients undergoing autologous fat grafting for oncologic head and neck reconstruction from 2005 to 2014. Aesthetic outcomes were rated by a group of 10 plastic surgeons and 10 laypersons using a five-point Likert scale.

Results:

A total of 190 fat grafting procedures were performed in 116 patients. Of these, 69 percent had received radiation therapy before their reconstructive surgery. The average number of treatments per patient was 1.6 ± 1 (range, 1 to 6), with a mean injection volume of 24.8 ± 20.2 ml. The mean follow-up time from the first fat grafting procedure was 35.8 ± 23.1 months. Complications occurred in 6 percent, none of which required a return to the operating room or hospital admission. Oncologic recurrence was observed in six patients (three local, one regional, and two distant). Locoregional recurrences were in areas outside of where the fat was grafted. Aesthetic analysis revealed that both plastic surgeons and laypersons thought patients appeared closer to normal following autologous fat grafting.

Conclusion:

This study suggests that autologous fat grafting plays a valuable role in enhancing aesthetic outcomes either by complementing or replacing reconstructive flaps for oncologic head and neck reconstruction while having both low complication rates and no evidence of being associated with cancer recurrence.
Fractional Carbon Dioxide Laser in Patients with Skin Phototypes III to VI and Facial Burn Sequelae: 1-Year Follow-Up
Authors: Salles Alessandra Grassi , Luitgards Bruno Ferreira , Moraes Luciana Borsoi , Remigio Adelina Fátima do Nascimento , Zampieri Ligia Araújo , Gemperli Rolf
Published: August 2018

Background:

Fractional carbon dioxide laser treatment in postburn scars is safe and effective, but high rates of hypochromia (35 percent) have been described in patients with skin phototypes V and VI after 2 months. The authors evaluated the efficacy and safety of fractional carbon dioxide laser treatment of burn scars in skin phototypes III to VI after 1 year, focusing on the incidence of hypochromia.

Methods:

A case series of 20 patients had skin phototypes III to VI with facial burn sequelae. They underwent three sessions of fractional laser. Laser fluence was increased in patients with no hypochromia and reepithelialization time of less than 15 days. Scars were evaluated after 2 months and 1 year by a five-item scale: color, hydration, surface irregularities, volume, and distensibility.

Results:

The mean time for reepithelialization was 13.3 days (range, 2 to 40 days). The average final score of the scale increased from 4.4 before treatment to 7.33 after 1 year for physicians, and from 5.35 to 7.5 for patients. There was also an increase in the subjective score, which patients used to assess their skin. Two months after treatment, 60 percent of patients presented with punctate hypochromia. After 1 year, only 15 percent of patients still had mild hypochromia; all of them had skin phototypes V and VI. Nevertheless, they were satisfied with overall bleaching of the skin.

Conclusions:

Fractional carbon dioxide laser improved skin quality. Late punctate hypopigmentation should be considered a possible complication in patients with skin phototypes V and VI.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Integrated Genomic Analysis of Hypoxia Genes across Cancer Types Identifies Significant Associations with Cancer Hallmarks
Authors: Yang Lingjian , Forker Laura , Fjeldbo Christina S. , Bristow Robert G. , Lyng Heidi , West Catharine M. L.
Published: August 2018

Hypoxia is a generic micro-environmental factor in most solid tumours. While most published literature focused onin vitroor single tumour type investigations, we carried out the first multi-omics pan cancer analysis of hypoxia with the aim of gaining a comprehensive understanding of its implication in tumour biology. A core set of 52 mRNAs were curated based on experimentally validated hypoxia gene sets from multiple cancer types. The 52 mRNAs collectively stratified high- and low-hypoxia tumours from The Cancer Genome Atlas (TCGA) database (9698 primary tumours) in each of the 32 cancer types available. High- hypoxia tumours had high expression of not only mRNA but also protein and microRNA markers of hypoxia. In a pan cancer transcriptomic analysis, ≥70% of the known cancer hallmark pathways were enriched in high-hypoxia tumours, most notably epithelial mesenchymal transition potential, proliferation (G2M checkpoint, E2F targets, MYC targets) and immunology response. In a multi-omics analysis, gene expression-determined high- hypoxia tumours had a higher non-silent mutation rate, DNA damage repair deficiency and leukocyte infiltration. The associations largely remained significant after correcting for confounding factors, showing a profound impact of hypoxia in tumour evolution across cancer types. High-hypoxia tumours determined using the core gene set had a poor prognosis in 16/32 cancer types, with statistical significances remaining in five after adjusting for tumour stage and omics biomarkers. In summary, this first comprehensivein vivomap of hypoxia in cancers highlights the importance of this micro-environmental factor in driving tumour progression.
Methyl-CpG-binding domain 9 (MBD9) is required for H2A.Z incorporation into chromatin at a subset of H2A.Z-enriched regions in the Arabidopsis genome
Authors: Sijacic Paja , Holder Dylan H. , Bajic Marko , Deal Roger B.
Published: August 2018

The SWR1 chromatin remodeling complex, which deposits the histone variant H2A.Z into nucleosomes, has been characterized in yeast and animals but had not been purified from plants. We used the conserved SWR1 subunit ACTIN RELATED PROTEIN 6 (ARP6) as bait in tandem affinity purification experiments to isolate associated proteins from Arabidopsis thaliana. We identified all 11 subunits found in yeast SWR1 and the homologous mammalian SRCAP complexes, demonstrating that this complex is conserved in plants. We also identified several additional proteins not previously associated with SWR1, including Methyl-CpG-BINDING DOMAIN 9 (MBD9). Since mbd9 mutant plants were phenotypically similar to arp6 mutants, we further explored a potential role for MBD9 in H2A.Z deposition. We found that MBD9 is required for proper H2A.Z incorporation at thousands of discrete sites, which represent a subset of the regions normally enriched with H2A.Z. Genetic analyses showed that arp6;mbd9 double mutants have far more severe phenotypes than either single mutant. In conjunction with the finding that MBD9 does not appear to be a core subunit of the Arabidopsis SWR1 complex, this suggests that MBD9 also has important roles beyond H2A.Z deposition. Our data establish the SWR1 complex as being conserved across eukaryotes and also provide new insights into the mechanisms that target H2A.Z to chromatin.