bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness Analysis of a Part-Time Rapid Response System During Operation Versus Nonoperation*
Authors: Kim Youlim , Lee Dong Seon , Min Hyunju , Choi Yun Young , Lee Eun Young , Song Inae , Park Jong Sun , Cho Young-Jae , Jo You Hwan , Yoon Ho Il , Lee Jae Ho , Lee Choon-Taek , Do Sang Hwan , Lee Yeon Joo
Published: March 2017

Objectives:

To evaluate the effect of a part-time rapid response system on the occurrence rate of cardiopulmonary arrest by comparing the times of rapid response system operation versus nonoperation.

Design:

Retrospective cohort study.

Setting:

A 1,360-bed tertiary care hospital.

Patients:

Adult patients admitted to the general ward were screened. Data were collected over 36 months from rapid response system implementation (October 2012 to September 2015) and more than 45 months before rapid response system implementation (January 2009 to September 2012).

Interventions:

None.

Measurements and Main Results:

The rapid response system operates from 7 am to 10 pm on weekdays and from 7 am to 12 pm on Saturdays. Primary outcomes were the difference of cardiopulmonary arrest incidence between pre-rapid response system and post-rapid response system periods and whether the rapid response system operating time affects the cardiopulmonary arrest incidence. The overall cardiopulmonary arrest incidence (per 1,000 admissions) was 1.43. Although the number of admissions per month and case-mix index were increased (3,555.18 vs 4,564.72, p < 0.001; 1.09 vs 1.13, p = 0.001, respectively), the cardiopulmonary arrest incidence was significantly decreased after rapid response system (1.60 vs 1.23; p = 0.021), and mortality (%) was unchanged (1.38 vs 1.33; p = 0.322). After rapid response system implementation, the cardiopulmonary arrest incidence significantly decreased by 40% during rapid response system operating times (0.82 vs 0.49/1,000 admissions; p = 0.001) but remained similar during rapid response system nonoperating times (0.77 vs 0.73/1,000 admissions; p = 0.729).

Conclusions:

The implementation of a part-time rapid response system reduced the cardiopulmonary arrest incidence based on the reduction of cardiopulmonary arrest during rapid response system operating times. Further analysis of the cost effectiveness of part-time rapid response system is needed.
Modeling Flowsheet Data to Support Secondary Use
Authors: Westra Bonnie L. , Christie Beverly , Johnson Steven G. , Pruinelli Lisiane , LaFlamme Anne , Sherman Suzan G. , Park Jung In , Delaney Connie W. , Gao Grace , Speedie Stuart
Published: March 2017

The purpose of this study was to create information models from flowsheet data using a data-driven consensus-based method. Electronic health records contain a large volume of data about patient assessments and interventions captured in flowsheets that measure the same “thing,” but the names of these observations often differ, according to who performs documentation or the location of the service (eg, pulse rate in an intensive care, the emergency department, or a surgical unit documented by a nurse or therapist or captured by automated monitoring). Flowsheet data are challenging for secondary use because of the existence of multiple semantically equivalent measures representing the same concepts. Ten information models were created in this study: five related to quality measures (falls, pressure ulcers, venous thromboembolism, genitourinary system including catheter-associated urinary tract infection, and pain management) and five high-volume physiological systems: cardiac, gastrointestinal, musculoskeletal, respiratory, and expanded vital signs/anthropometrics. The value of the information models is that flowsheet data can be extracted and mapped for semantically comparable flowsheet measures from a clinical data repository regardless of the time frame, discipline, or setting in which documentation occurred. The 10 information models simplify the representation of the content in flowsheet data, reducing 1552 source measures to 557 concepts. The amount of representational reduction ranges from 3% for falls to 78% for the respiratory system. The information models provide a foundation for including nursing and interprofessional assessments and interventions in common data models, to support research within and across health systems.
β-Blocker use and reduced disease progression in patients with thick melanoma: 8 years of follow-up
Authors: De Giorgi Vincenzo , Grazzini Marta , Benemei Silvia , Marchionni Niccolò , Geppetti Pierangelo , Gandini Sara
Published: March 2017

Previous observational studies have reported the protective effect of β-blockers on the progression of different types of cancers. In 2011, we published a prospective study, including patients with histologically confirmed malignant melanoma in stage II–IIIA. In total, 25% of them reported previous use of β-blockers that were administered at any time for any other diseases. After a median follow-up of 2.5 years, 34% of the patients in the untreated group showed disease progression. In contrast, only 3% of the patients in the treated group showed progression. We report the findings obtained in the same cohort after a longer period of β-blocker therapy and follow-up (8 years). We prospectively reviewed data of the patients enrolled in the original prospective study. Disease progression was assessed by evaluating the presence of lymphatic, in-transit or visceral metastases. Deaths by any cause and deaths because of melanoma were recorded. A multivariate Cox proportional hazards model was used to evaluate the effect of β-blocker use on disease-free survival and overall survival, adjusting for significant confounders. After a median follow-up of 8 years and a median duration of β-blocker use of 7.6 years, 45% of the patients in the untreated group and 30% of the patients in the treated group showed disease progression. Notably, in the untreated group 35% patients died from melanoma and only 17% patients died from melanoma in the treated group. Results of this hospital-based prospective cohort study with a median follow-up of 8 years confirmed our previous results that the use of β-blockers significantly reduced the risk of recurrence and mortality in melanoma patients.
Splash Safety During Dermatologic Procedures Among US Dermatology Residents
Authors: Korta Dorota Z. , Chapman Lance W. , Lee Patrick K. , Linden Kenneth G.
Published: March 2017

BACKGROUND

Dermatologists are at potential risk of acquiring infections from contamination of the mucous membranes by blood and body fluids. However, there are little data on splash safety during procedural dermatology.

OBJECTIVE

To determine dermatology resident perceptions about splash risk during dermatologic procedures and to quantify the rate of protective equipment use.

METHODS

An anonymous on-line survey was sent to 108 United States ACGME-approved dermatology residency programs assessing frequency of facial protection during dermatologic procedures, personal history of splash injury, and, if applicable, reasons for not always wearing facial protection.

RESULTS

A total of 153 dermatology residents responded. Rates of facial protection varied by procedure, with the highest rates during surgery and the lowest during local anesthetic injection. Over 54% of respondents reported suffering facial splash while not wearing facial protection during a procedure. In contrast, 88.9% of respondents correctly answered that there is a small risk of acquiring infection from mucosal splash. Residency program recommendations for facial protection seem to vary by procedure.

CONCLUSION

The authors' results demonstrate that although facial splash is a common injury, facial protection rates and protective recommendations vary significantly by procedure. These data support the recommendation for enhanced facial protection guidelines during procedural dermatology.
Histological Mohs Maps Improve the Accuracy of Dermatology Residents' Interpretations of Mohs Slides: A Pilot Study
Authors: Tiger Jeffrey B. , Ganesh Zai , Mouzakis John , Iwamoto Satori
Published: March 2017

BACKGROUND

Effective Mohs surgery depends on accurate histopathological identification and mapping of tumor burden to ensure complete removal of tumor.

OBJECTIVE

The purpose of this study is to evaluate whether using a photograph of the histopathological slide as the Mohs map improves mapping accuracy.

MATERIALS AND METHODS

Single-blinded pilot study. Five dermatology residents at one academic institution mapped 11 cases of basal cell carcinoma using both traditional hand-drawn maps and color photographic maps. Residents' marked maps were assessed for global diagnostic accuracy, sensitivity, and specificity compared with the Mohs map verified by the attending surgeon on the day of surgery.

RESULTS

Diagnostic accuracy, sensitivity, and specificity were higher using the photographic Mohs maps compared with using the traditional hand-drawn maps (58.2% vs 29.1%, 84.5% vs 76.4%, and 87.1% vs 70.8%, respectively). These results were statistically significant for accuracy and specificity, but not for sensitivity.

CONCLUSION

Using histopathological photographs as the Mohs map significantly improved accuracy and specificity within a small group of residents with limited Mohs experience. More research is warranted to evaluate whether using histopathological photographs improves accuracy of Mohs mapping for experienced Mohs surgeons in a real-world setting, and whether this translates to improved clinical outcomes.
IGG4-RELATED OPHTHALMIC DISEASE PRESENTING AS CHOROIDAL AND ORBITAL LESIONS
Authors: Gange William S. , Holland Stephen M. , De Alba Felipe
Published: March 2017

Purpose:

To report a case of IgG4-related ophthalmic disease (IgG4-ROD) which presented as choroidal and orbital lesions.

Methods:

Case report.

Results:

A 64-year-old man presented with left eye photopsias and a history of IgG4-related perirenal fibrosis. Fundoscopic examination showed multiple bilateral yellow choroidal lesions, and optical coherence tomography showed multiple choroidal lesions. Magnetic resonance imaging of the orbits showed an enhancing lesion present circumferential to the optic nerve, but greater medially, abutting the posterior surface of the left globe. Workup for infectious, autoimmune, and malignant etiologies was negative, and the patient has responded well to treatment with rituximab.

Conclusion:

IgG4-related disease is a systemic fibroinflammatory disease, which often presents in another location, as in our patient. In cases of uncertain choroidal and orbital lesions, a thorough workup for other etiologies is indicated, and lymphoma must be ruled out. Steroids are the mainstay of treatment for IgG4-ROD, however, small case series and our patient responded well to rituximab. To our knowledge, this is the first reported case of choroidal and orbital lesions secondary to IgG4-ROD.
MANAGEMENT OF METASTATIC BREAST CARCINOMA OF IRIS WITH INTRAOCULAR BEVACIZUMAB INJECTIONS
Authors: Akinci G. Ece , Hondur Ahmet M. , Tezel Tongalp H.
Published: March 2017

Purpose:

To describe intraocular use of bevacizumab for a metastatic breast carcinoma of the iris resistant to advanced systemic chemotherapy protocols, for which conventional treatment would be local radiotherapy or brachytherapy.

Methods:

Case report.

Results:

A 65-year-old woman, who was previously diagnosed with breast carcinoma and treated with radical mastectomy coupled with radiotherapy and chemotherapy, presented with an iris mass in her left eye. Four successive intravitreal injections of bevacizumab resulted in progressive regression of the tumor to an almost indiscernible size at 8 months, along with blunting of the highly complex tumor vascular network on fluorescein angiography. At 12 months, the patient's visual acuity remained 20/20, and no ocular or systemic adverse effects were encountered.

Conclusion:

Intravitreal bevacizumab can offer a simpler and safer solution to treat metastatic iris tumors compared with other treatment options. This report of bevacizumab for treating iris metastasis from breast carcinoma may broaden the treatment options for similar neoplasms of the iris.
Myopic Laser Corneal Refractive Surgery Reduces Interdevice Agreement in the Measurement of Anterior Corneal Curvature
Authors: Jin Haiying , Ou Zhongmin , Guo Haike , Zhao Peiquan
Published: March 2017

Objectives:

To investigate interdevice differences and agreement in the measurement of anterior corneal curvature obtained by different technologies after laser corneal refractive surgery.

Methods:

The prospective study comprised 109 eyes of 109 consecutive patients who had undergone laser-assisted in situ keratomileusis (LASIK). Preoperative and postoperative corneal parameters were measured by Scheimpflug imaging (Pentacam), Placido-slit-scanning (Orbscan) and auto-keratometry (IOLMaster). Preoperative and postoperative anterior corneal curvatures (K readings) were compared between devices. Interdevice agreement was evaluated by Bland–Altman analysis.

Results:

Preoperatively, the difference of K reading for Pentacam–IOLMaster (0.04±0.20 D) was not statistically significant (P=0.059). The differences between Pentacam–Orbscan and Orbscan–IOLMaster were 0.20±0.34 D (P<0.001) and −0.17±0.29 D (P<0.001), respectively. After surgery, no difference was found for Pentacam–Orbscan (−0.05±0.38, P=0.136). The differences between Pentacam–IOLMaster and Orbscan–IOLMaster were 0.13±0.29 D (P<0.001) and 0.19±0.34 D (P<0.001). Preoperative interdevice agreement (95% limit of agreement [LOA]) between Pentacam and Orbscan, Pentacam and IOLMaster, and Orbscan and IOLMaster were 1.31 D, 0.79 D and 1.14 D, respectively. The 95% LOAs decreased to 1.47 D, 1.14 D, and 1.34 D after refractive surgery.

Conclusion:

Corneal refractive surgery changed the preoperative and postoperative interdevice differences in corneal curvature measurements and reduced interdevice agreement, indicating that the devices are not interchangeable.
Sub-basal Corneal Nerve Plexus Analysis Using a New Software Technology
Authors: Batawi Hatim , Shalabi Nabeel , Joag Madhura , Koru-Sengul Tulay , Rodriguez Jorge , Green Parke T. , Campigotto Mauro , Karp Carol L. , Galor Anat
Published: March 2017

Purpose:

To study sub-basal corneal nerve plexus (SCNP) parameters by in vivo corneal confocal microscopy using a new software technology and examine the effect of demographics and diabetes mellitus (DM) on corneal nerves morphology.

Methods:

A Confoscan 4 (Nidek Technologies) was used in this cross-sectional study to image the SCNP in 84 right eyes at the Miami Veterans Affairs eye clinic. Images were analyzed using a new semiautomated nerve analysis software program (The Corneal Nerve Analysis tool) which evaluated 9 parameters including nerve fibers length (NFL) and nerve fibers length density (NFLD). The main outcome measure was the examination of SCNP morphology by demographics, comorbidities, and HbA1c level.

Results:

Interoperator and intraoperator reproducibility were good for the 9 parameters studied (Intraclass Correlations [ICCs] 0.73–0.97). Image variability between two images within the same scan was good for all parameters (ICC 0.66–0.80). Older individuals had lower SCNP parameters with NFL and NFLD negatively correlating with age (r=−0.471, and −0.461, respectively, P<0.01 for all). Patients with diabetes had lower mean NFLD 10987.6 μm/mm2 (±3,284.6) and NFL 1,289.5 μm/frame (±387.2) compared with patients without diabetes (mean NFLD 15077.1 μm/mm2 [±4,261.3] and NFL 1750.0 μm/frame [±540.7]) (P<0.05 for all). HbA1c levels in patients with diabetes were inversely correlated with NFL and NFLD (r= −0.568, and −0.569, respectively, P<0.05 for all).

Conclusions:

The Corneal Nerve Analysis tool is a reproducible diagnostic software technique for the analysis of the SCNP with confocal microscopy. Older age, DM, and higher level of HbA1c were associated with a significant reduction in SCNP parameters.
Conjunctivochalasis and Related Factors in an Adult Population of Iran
Authors: Hashemi Hassan , Rastad Hadith , Emamian Mohammad Hassan , Fotouhi Akbar
Published: March 2017

Objectives:

To determine the prevalence of conjunctivochalasis and its determinants in a middle-aged Iranian population.

Methods:

This population-based study was conducted in the context of the second phase of Shahroud Eye Cohort Study in 2014. Of 4,737 participants aged 45 to 69 years who participated in the second phase, the data of 4,702 participants were available for this report. A diagnosis of conjunctivochalasis was made based on the physician's judgment on ophthalmic examinations.

Results:

Diagnosis of conjunctivochalasis in at least one eye was confirmed in 295 (6.2%) participants. The prevalence of unilateral and bilateral conjunctivochalasis was 0.7% and 5.5%, respectively. Older age (odds ratio [OR] = 1.96, 95% confidence interval [CI]: 1.22–3.15), use of Losartan (an angiotensin II receptor antagonist) (OR=1.47, 95% CI: 1.05–2.08), Meibomian Gland Dysfunction (OR=2.32, 95% CI: 1.78–3.03), Pinguecula (OR=0.57, 95% CI: 0.42–0.77), and blepharitis (OR=0.24, 95% CI: 0.07–0.77) had a significant association with conjunctivochalasis.

Conclusion:

The prevalence of conjunctivochalasis in our study was less than other reports from Asian population. Conjunctivochalasis has a significant association with some eyelid disorders and the use of Losartan which should be noted when diagnosing and treating this disease.
Advantages of Minimal Access versus Conventional Aortic Valve Replacement in Elderly or Severely Obese Patients
Authors: Pisano Calogera , Totaro Pasquale , Triolo Oreste Fabio , Argano Vincenzo
Published: March 2017

Objective

The aim of our study was to investigate potential clinical advantages of minimal access versus conventional surgical approach in older and severely obese patients undergoing isolated aortic valve replacement (AVR).

Methods

One hundred thirty-five patients undergoing isolated primary AVR were enrolled. Propensity score matching was used to compare 42 selected patients operated on ministernotomy (MS, group B) with 42 selected patients operated on full sternotomy (FS, group A).

Results

After propensity score matching, the two groups were comparable in terms of preoperative characteristics. Cardiopulmonary bypass time was significantly longer in MS group compared with the FS group [median (95% confidence level or CL), 103 (98.7–106.4) vs 94 (83.6–99) minutes, respectively; P = 0.0019]. No significant difference was observed in aortic cross-clamp time [median (95% CL), 73 (71.1–78.2) vs 69.5 (62.7–83) minutes; P = 0.4]. Significantly shorter ventilation time [median (95% CL), 13 (12–16.4) vs 24 (22–25) hours; P = 0.00018], intensive care unit stay [median (95% CL), 1 vs 2 days; P = 0.00017], and hospital stay [median (95% CL), 8.5 (8–10.8) vs 13.5 (11.1–14) days; P = 0.00030] were shown in the MS group. The age subgroup analysis showed that statistical significance for mechanical ventilation, intensive care unit, and hospital stay was specific for patients older than 75 years. The analysis of body mass index quartile showed that statistical significance for mechanical ventilation was specific for patients in the fourth quartile.

Conclusions

Minimal access AVR is a reproducible, safe, and effective surgical option in patients candidate for isolated AVR, and our study suggests a faster recovery when used in severely obese or older patients.
Modeling Outcomes
Authors: Nellis Joseph R. , Chung Timothy K. , Agarwal Nandita , Torres Jose E. , Holgren Sarah E. , Raghavan Madhavan L. , Turek Joseph W.
Published: March 2017

Objective

Numerous surgical approaches regarding aortic arch advancement for neonatal arch hypoplasia have been described. These repairs can be classified into two categories: those that incorporate a patch and those that do not. The decision between repairs remains largely experiential, rather than empirical, because of the limited number of reported outcomes. We report early outcomes from neo-nates undergoing modified aortic arch advancement with an anterior patch and our experience using computational fluid dynamic modeling to better understand the hemodynamic consequences associated with this repair.

Methods

A retrospective review of neonates undergoing aortic arch advancement with anterior patch in 2014 at a single institution was performed. Anatomical, perioperative, and follow-up data were collected. Three-dimensional cardiac magnetic resonance images were used to generate computational fluid dynamic models of the modified anterior patch and direct end-to-side repairs. Cardiac waveform inputs were simulated and hemodynamic analyzed.

Results

Ten neonates underwent modified aortic arch advancement. No hemodynamically significant gradients were observed at a median follow-up of 0.77 (0.30–1.2) years. Asymmetrical flow was observed in the end-to-side repair, whereas more concentric laminar flow was observed throughout the modified model. Spatial variations in velocities immediately distal to the anastomosis were greater in the end-to-side model (0.35 vs 0.17 m/s, P < 0.001). Time-averaged variations in wall shear stress during systole were greater in the end-to-side model at the same location (3.44 vs 1.98 dynes/cm2, P <0.001).

Conclusions

Early outcomes after the use of an anterior patch for neonatal hypoplastic aortic arch repair show favorable hemodynamic outcomes.
Continuity of Care in Older Adults With Multiple Chronic Conditions: How Well Do Administrative Measures Correspond With Patient Experiences?
Authors: DuGoff Eva H.
Published: March 2017

Continuity of care (COC) is a fundamental component of primary care and particularly important to older adults who are managing multiple chronic conditions. Administrative measures of continuity are often used to evaluate care coordination interventions, but it is not known whether administrative continuity are correlated with patient reports of continuity among older adults with multiple chronic conditions (MCCs). The objective of this study is to assess the concordance of administrative continuity indices and patient reports of continuity among older adults with MCCs. We use patient survey data collected from July to October 2011 linked to administrative claims data collected from July 2010 to December 2011 for 710 Medicare Advantage Chronic Care Special Needs Plan beneficiaries living in the US South. Among older adults with two or more conditions, the Usual Provider of Care Index was not associated with any patient experience measure; COC Index was associated with informational and management continuity items. These findings suggest that among older adults with MCCs, the administrative continuity measures have limited concordance with patient reported continuity measures.
Analysis of a Patient Intervention to Reduce Patients Who Leave Without Being Seen in an Ophthalmology-Dedicated Emergency Room
Authors: Lorch Alice C. , Martinez Maureen , Gardiner Matthew
Published: March 2017

Patients who leave without being seen (LWBS) by a medical provider in emergency care settings are a concern because their urgent complaints remain unaddressed. This study aims to characterize the LWBS population in an ophthalmology-dedicated emergency room and to evaluate an intervention designed to decrease the number of these patients. A program of rounding and patient contact in the waiting room of our emergency room was initiated to this end. A patient database was used retrospectively to review 13,124 charts and collect clinical and demographic data on 71 LWBS patients. The percentage of LWBS patients decreased from 0.74% to 0.33% after the intervention (p = 0.00158). Of the LWBS patients, 27% were seen in an ophthalmology clinic within 2 weeks, and 4% were seen back in the emergency room. Of these patients, 49% had some ophthalmology follow-up after leaving. Among those with follow-up, 14% had concerning pathology. Of all LWBS patients, 63% had a primary care physician. We conclude that frequent rounding in an emergency room waiting room can decrease the number of LWBS patients and as such reduce morbidity. This strategy offers potential to improve healthcare outcomes in emergency settings.
A Six Sigma Approach to Analyze Time-to-Assembly Variance of Surgical Trays in a Sterile Services Department
Authors: Fogliatto Flavio S. , Anzanello Michel J. , Tortorella Guilherme L. , Schneider Daniela S. S. , Pereira Cintia G. R. , Schaan Beatriz D.
Published: March 2017

Introduction:

We analyze the assembly of surgical trays in a hospital's sterile services department. The department assembles 520 different tray setups. However, tray assembly times are unknown, imposing a challenge to production planners. To respond to demand, workers from other departments are often called, leading to higher operational costs and more frequent quality problems due to workers' poor training and inconsistency.

Methods:

Conducting traditional time-motion studies is infeasible in such a high variety production setting. Thus, we used design of experiments to optimize the data acquisition. Assembly times of 36 trays were sampled using a 2-factor nested factorial design. Through regression analysis, we built a model to estimate completion times of trays not sampled in the experiment.

Results:

A prediction model with 90.8% accuracy was obtained from the experimental data. The model was validated with assembly times from several trays not included in the experiment. Predicted assembly times had an absolute error of 7.83% on average compared with observed assembly times.

Conclusions:

Design of experiments and regression analysis combined were able to optimize time data acquisition using a small sample of trays, resulting in a model that predicted assembly times within an acceptable margin of error.
Round and Oval Window Anatomic Variability: Its Implication for the Vibroplasty Technique
Authors: Mancheño Marta , Aristegui Miguel , Sañudo Jose Ramon
Published: March 2017

Objective:

The objective of this study is to evaluate the anatomical variability of round and oval window regions and its relationship with their closest structures, to determine its implication on the fitting and stabilization of the middle ear implant Vibrant Soundbridge.

Methods:

Variations of the anatomy of round and oval window regions were assessed in a total of 85 human dissected temporal bones. Afterward, we evaluated the adaptation and subsequent stabilization of the floating mass transducer (FMT) of the Vibrant Soundbridge in 67 cases in round window (RW) and in 22 cases in oval window (OW), and the influence that the variability of the different anatomical features examined had on this stabilization. We also assessed access and surgeon's view of the RW niche through the facial recess approach.

Results:

Stabilization of the FMT in the RW was achieved in 53 (79%) of the 67 cases; we found that the less favorable anatomical conditions for stabilization were: membrane smaller than 1.5 mm, presence of a high jugular bulb and a narrow or very narrow RW niche. Frequently, two or more of these conditions happened simultaneously. In seven cases (22%) access to the RW through facial recess approach did not allow positioning the FMT in place. OW stabilization succeeded in 18 (82%) of the 22 cases.

Conclusion:

Round and oval window vibroplasty are difficult surgical techniques. To place the FMT directly on the OW may be easier as we do not have to drill the niche. In both regions there are some anatomical conditions that hinder fitting the FMT and even make it impossible. Once fitted, the main problem is to achieve good stabilization of the device.
Comparison of Experts and Residents Performing a Complex Procedure in a Temporal Bone Surgery Simulator
Authors: Ioannou Ioanna , Zhou Yun , Wijewickrema Sudanthi , Piromchai Patorn , Copson Bridget , Kennedy Gregor , O’Leary Stephen
Published: March 2017

Objective:

To investigate the use of automated metrics from a virtual reality (VR) temporal bone surgery simulator to determine how the performance of experts and trainees differs when performing a complex otological procedure (mastoidectomy with posterior tympanotomy and cochleostomy).

Study Design:

Cohort study.

Methods:

Using the University of Melbourne VR temporal bone surgery simulator, seven ENT consultants and seven ENT residents performed two trials of the surgical approach to cochlear implantation on a virtual temporal bone. Simulator recordings were used to calculate a range of automated metrics for each stage of the procedure, capturing efficiency, technique characteristics, drilled bone regions, and damage to vital anatomical structures.

Results:

Results confirm that experts drilled more efficiently than residents. Experts generally used larger burrs and applied higher forces, resulting in faster material removal. However, they exercised more caution when drilling close to anatomical structures. Residents opened the temporal bone more widely, but neglected important steps in obtaining a clear view toward the round window, such as thinning the external ear canal wall and skeletonizing the medial aspect of the facial nerve. Residents used higher magnification and reoriented the temporal bone more often than experts.

Conclusion:

VR simulation provides metrics that allow the objective analysis of surgical technique, and identification of differences between the performance of surgical residents and their senior colleagues. The performance of residents could be improved with more guidance regarding how much force they should apply, what burr size they should use, how they should orient the bone, and for cochlear implant surgery guidance regarding anatomical regions requiring particular attention, to visualize the round window.
Clinical efficacy and tolerability of direct-acting antivirals in elderly patients with chronic hepatitis C
Authors: Sherigar Jagannath M. , Gayam Vijay , Khan Arifa , Mukhtar Osama , Arefiev Yavgeniy , Khalid Mazin , Siddiqui Imran , Rangaraju Ayyappa M. , Budhathoki Nibash , Mansour Mohammed , Guss Debra , Mohanty Smruti R.
Published: March 2017

Background

There is a lack of evidence-based data on aged patients with newer direct-acting antivirals (DAAs) and with shorter duration of treatment regimens involving DAAs with or without ribavirin (RBV) and pegylated interferon (Peg IFN).

Patients and methods

Medical records of 240 patients treated with DAAs with or without Peg IFN and RBV between January 2013 and July 2015 were retrospectively analyzed. Patients were divided into two groups: patients aged 65 years and older (N=84) and patients aged younger than 65 years (N=156). Pretreatment baseline patient characteristics, treatment efficacy, factors affecting sustained virologic response at 12 weeks after treatment, and adverse reactions were compared between the groups.

Results

No statistically significant difference was observed with end of treatment response (98.8 vs. 98%, P=0.667) and sustained virologic response at 12 weeks after treatment (93.1 vs. 94.1%, P=0.767) between patients aged 65 and older and those younger than 65 years of age. Fatigue was the most common adverse event recorded (32.5%), followed by anemia (19.6%), leukopenia (11.7%), thrombocytopenia (10%), skin rash (8.3%), and headache (7.9%). The RBV dose was reduced in eight (8%) patients and four patients discontinued the RBV treatment because of severe anemia. RBV dose reduction or discontinuation did not reach statistical significance (P=0.913). Increased fibrosis, cirrhosis, aspartate aminotransferase, alanine aminotransferase, hemoglobin, and platelet levels seem to affect the sustained virologic response in the elderly. Twelve (6.28%) patients failed to respond to treatment and the failure rate was not significant (P=0.767) between the groups.

Conclusion

DAAs with or without IFN and RBV in the standard recommended 12 or 24-week treatment regimens are effective, well tolerated, and may be safely extended to elderly patients infected with chronic hepatitis C.
Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals
Authors: Kelesidis Theodoros , Oda Michael N. , Borja Mark S. , Yee Yumin , Ng Kit F. , Huynh Diana , Elashoff David , Currier Judith S.
Published: March 2017

Objective:

High-density lipoprotein (HDL) function rather than absolute level may be a more accurate indicator for cardiovascular disease (CVD). Novel methods can measure HDL function using patient samples. The objective of this study is to identify factors that may contribute to HDL dysfunction in chronic treated HIV-1 infection.

Design:

Retrospective study of HDL function measured in 2 ways in HIV-1–infected men with low overall CVD risk and healthy men with no known CVD risk matched by race to the HIV-1–infected participants.

Methods:

We examined patient-level factors associated with 2 different measures of HDL dysfunction: reduced antioxidant function (oxidized HDL, HDLox) and reduced HDL-apoA-I exchange (HAE), a measure of HDL remodeling, in the HIV infected and control men. Multivariable-adjusted linear regression analyses were used adjusting for false discovery rate, age, race, body mass index (BMI), CD4 count, viremia, CVD risk, smoking, lipids, apoA-I, and albumin.

Results:

In multivariate analysis among HIV-1–infected men (n = 166) (median age 45 years, CD4 T-cell count 505 cells/mm3, 30.1% were viremic), higher BMI, lower apoA-I, and lower albumin were among the most notable correlates of higher HDLox and lower HAE (P< 0.05). In HIV-1 uninfected participants, lower albumin and higher BMI were associated with lower HAE and higher HDLox, respectively (P≤ 0.05). HDLox was inversely related to HAE in HIV-1–infected individuals (P< 0.001).

Conclusions:

Increased HDLox correlates with reduced HAE in chronic HIV-1 infection. Higher BMI, lower apoA-I, and albumin were identified as factors associated with HDL dysfunction in chronic HIV-1 infection using 2 independent methods.
Environmental perturbations lead to extensive directional shifts in RNA processing
Authors: Richards A. L. , Watza D. , Findley A. , Alazizi A. , Wen X. , Pai A. A. , Pique-Regi R. , Luca F.
Published: March 2017

Environmental perturbations have large effects on both organismal and cellular traits, including gene expression, but the extent to which the environment affects RNA processing remains largely uncharacterized. Recent studies have identified a large number of genetic variants associated with variation in RNA processing that also have an important role in complex traits; yet we do not know in which contexts the different underlying isoforms are used. Here, we comprehensively characterized changes in RNA processing events across 89 environments in five human cell types and identified 15,300 event shifts (FDR = 15%) comprised of eight event types in over 4,000 genes. Many of these changes occur consistently in the same direction across conditions, indicative of global regulation by trans factors. Accordingly, we demonstrate that environmental modulation of splicing factor binding predicts shifts in intron retention, and that binding of transcription factors predicts shifts in AFE usage in response to specific treatments. We validated the mechanism hypothesized for AFE in two independent datasets. Using ATAC-seq, we found altered binding of 64 factors in response to selenium at sites of AFE shift, including ELF2 and other factors in the ETS family. We also performed AFE QTL mapping in 373 individuals and found an enrichment for SNPs predicted to disrupt binding of the ELF2 factor. Together, these results demonstrate that RNA processing is dramatically changed in response to environmental perturbations through specific mechanisms regulated by trans factors.

Author Summary

Changes in a cell’s environment and genetic variation have been shown to impact gene expression. Here, we demonstrate that environmental perturbations also lead to extensive changes in alternative RNA processing across a large number of cellular environments that we investigated. These changes often occur in a non-random manner. For example, many treatments lead to increased intron retention and usage of the downstream first exon. We also show that the changes to first exon usage are likely dependent on changes in transcription factor binding. We provide support for this hypothesis by considering how first exon usage is affected by disruption of binding due to treatment with selenium. We further validate the role of a specific factor by considering the effect of genetic variation in its binding sites on first exon usage. These results help to shed light on the vast number of changes that occur in response to environmental stimuli and will likely aid in understanding the impact of compounds to which we are daily exposed.
Towards water-free biobanks: long-term dry-preservation at room temperature of desiccation-sensitive enzyme luciferase in air-dried insect cells
Authors: Kikuta Shingo , Watanabe Shunsuke J. , Sato Ryoichi , Gusev Oleg , Nesmelov Alexander , Sogame Yoichiro , Cornette Richard , Kikawada Takahiro
Published: March 2017

Desiccation-tolerant cultured cells Pv11 derived from the anhydrobioticPolypedilum vanderplankiembryo endure complete desiccation because of their ametabolic state and resume their metabolism after rehydration. These features led us to develop a novel dry preservation technology for enzymes as it was still unclear whether Pv11 cells preserved an exogenous enzyme in the dry state. This study shows that Pv11 cells protect an exogenous desiccation-sensitive enzyme, luciferase, preserving the enzymatic activity even after dry storage for 372 days at room temperature. A process including pre-incubation with trehalose, dehydration, storage, and rehydration allowed Pv11 (Pvll-Luc) cells stably expressing luciferase to survive desiccation and still emit luminescence caused by luciferase after rehydration. Luminescence produced by luciferase in Pvll-Luc cells after rehydration did not significantly decrease in presence of a translation inhibitor, showing that the activity did not derive fromde novoenzyme synthesis following the resumption of cell metabolism. These findings indicate that the surviving Pv11 cells almost completely protect luciferase during desiccation. Lacking of the preincubation step resulted in the loss of luciferase activity after rehydration. We showed that preincubation with trehalose associated to induction of desiccation-tolerant related genes in Pv11 cells allowed effectivein vivopreservation of enzymes in the dry state.
Trichoderma reeseicomplete genome sequence, repeat-induced point mutation and partitioning of CAZyme gene clusters
Authors: Li Wan-Chen , Huang Chien-Hao , Chen Chia-Ling , Chuang Yu-Chien , Tung Shu-Yun , Wang Ting-Fang
Published: March 2017

Trichoderma reesei(Ascomycota, Pezizomycotina) QM6a is a model fungus for a broad spectrum of physiological phenomena, including plant cell wall degradation, industrial production of enzymes, light responses, conidiation, sexual development, polyketide biosynthesis and plant-fungal interactions. The genomes of QM6a and its high-enzyme producing mutants have been sequenced by second-generation-sequencing methods and are publicly available from the Joint Genome Institute (JGI). While these genome sequences have offered useful information for genomic and transcriptomic studies, their limitations and especially their short read lengths make them poorly suited for some particular biological problems, including assembly, genome-wide determination of chromosome architecture and genetic modification or engineering. We integrated Pacific Biosciences and Illumina sequencing platforms for the highest-quality genome assembly yet achieved, revealing seven telomere-to-telomere chromosomes (34,922,528 bp; 10877 genes) with 1630 newly-predicted genes and >1.5 Mb of new sequences. Most new sequences are located on AT-rich blocks, including 7 centromeres, 14 subtelomeres and 2329 interspersed AT-rich blocks. The seven QM6a centromeres separately consist of 24 conserved repeats and 37 putative centromere-encoded genes. These findings open up a new perspective for future centromere and chromosome architecture studies. Next, we demonstrate that sexual crossing readily induced cytosine-to-thymine point mutations on both tandem and unlinked duplicated sequences. We also show by bioinformatic analysis thatTrichoderma reeseihas evolved a robust repeat-induced point mutation (RIP) system to accumulate AT-rich sequences, with longer AT-rich blocks having more RIP mutations. The widespread distribution of AT-rich blocks correlates genome-wide partitions with gene clusters, explaining why clustering of genes has been reported to not influence gene expression inTrichoderma reesei. Compartmentation of ancestral gene clusters by AT-rich blocks might promote flexibilities that are evolutionarily advantageous in this fungus’ soil habitats and other natural environments. Our analyses, together with the complete genome sequence, provide a better blueprint for biotechnological and industrial applications.
Detection of cooperatively bound transcription factor pairs using ChIP-seq peak intensities and expectation maximization
Authors: Datta Vishaka , Siddharthan Rahul , Krishna Sandeep
Published: March 2017

Transcription factors (TFs) often work cooperatively, where the binding of one TF to DNA enhances the binding affinity of a second TF to a nearby location. Such cooperative binding is important for activating gene expression from promoters and enhancers in both prokaryotic and eukaryotic cells. Existing methods to detect cooperative binding of a TF pair rely on analyzing the sequence that is bound. We propose a method that uses, instead, only ChIP-seq peak intensities and an expectation maximization (CPI-EM) algorithm. We validate our method using ChIP-seq data from cells where one of a pair of TFs under consideration has been genetically knocked out. Our algorithm relies on our observation that cooperative TF-TF binding is correlated with weak binding of one of the TFs, which we demonstrate in a variety of cell types, includingE. coli, S. cerevisiaeandM. musculuscells. We show that this method performs significantly better than a predictor based only on the ChIP-seq peak distance of the TFs under consideration. This suggests that peak intensities contain information that can help detect the cooperative binding of a TF pair. CPI-EM also outperforms an existing sequence-based algorithm in detecting cooperative binding. The CPI-EM algorithm is available athttps://github.com/vishakad/cpi-em.
Contribution oftransregulatory eQTL to cryptic genetic variation inC. elegans
Authors: Snoek L. Basten , Sterken Mark G. , Bevers Roel P. J. , Volkers Rita J. M. , van’t Hof Arjen , Brenchley Rachel , Riksen Joost A. G. , Cossins Andrew , Kammenga Jan E.
Published: March 2017

Background

Cryptic genetic variation (CGV) is the hidden genetic variation that can be unlocked by perturbing normal conditions. CGV can drive the emergence of novel complex phenotypes through changes in gene expression. Although our theoretical understanding of CGV has thoroughly increased over the past decade, insight into polymorphic gene expression regulation underlying CGV is scarce. Here we investigated the transcriptional architecture of CGV in response to rapid temperature changes in the nematodeCaenorhabditis elegans. We analyzed regulatory variation in gene expression (and mapped eQTL) across the course of a heat stress and recovery response in a recombinant inbred population.

Results

We measured gene expression over three temperature treatments: i) control, ii) heat stress, and iii) recovery from heat stress. Compared to control, exposure to heat stress affected the transcription of 3305 genes, whereas 942 were affected in recovering animals. These affected genes were mainly involved in metabolism and reproduction. The gene expression pattern in recovering animals resembled both the control and the heat-stress treatment. We mapped eQTL using the genetic variation of the recombinant inbred population and detected 2626 genes with an eQTL in the heat-stress treatment, 1797 in the control, and 1880 in the recovery. Thecis-eQTL were highly shared across treatments. A considerable fraction of thetrans-eQTL (40-57%) mapped to 19 treatment specifictrans-bands. In contrast tocis-eQTL,trans-eQTL were highly environment specific and thus cryptic. Approximately 67% of thetrans-eQTL were only induced in a single treatment, with heat-stress showing the most uniquetrans-eQTL.

Conclusions

These results illustrate the highly dynamic pattern of CGV across three different environmental conditions that can be evoked by a stress response over a relatively short time-span (2 hours) and that CGV is mainly determined by response relatedtransregulatory eQTL.
Assembling metagenomes, one community at a time
Authors: van der Walt Andries J. , Van Goethem Marc W. , Ramond Jean-Baptiste , Makhalanyane Thulani P. , Reva Oleg , Cowan Don A.
Published: March 2017

Background

Metagenomics allows unprecedented access to uncultured environmental microorganisms. The analysis of metagenomic sequences facilitates gene prediction and annotation, and enables the assembly of draft genomes, including uncultured members of a community. However, while several platforms have been developed for this critical step, there is currently no clear framework for the assembly of metagenomic sequence data.

Results

To assist with selection of an appropriate metagenome assembler we evaluated the capabilities of nine prominent assembly tools on nine publicly-available environmental metagenomes, as well as three simulated datasets. Overall, we found that SPAdes provided the largest contigs and highestN50values across 6 of the 9 environmental datasets, followed by MEGAHIT and metaSPAdes. MEGAHIT emerged as a computationally inexpensive alternative to SPAdes, assembling the most complex dataset using less than 500 GB of RAM and within 10 hours.

Conclusions

We found that assembler choice ultimately depends on the scientific question, the available resources and the bioinformatic competence of the researcher. We provide a concise workflow for the selection of the best assembly tool.
Network analysis of patient flow in two UK acute care hospitals identifies key sub-networks for A&E performance
Authors: Bean Daniel M. , Stringer Clive , Beeknoo Neeraj , Teo James , Dobson Richard J. B.
Published: March 2017

The topology of the patient flow network in a hospital is complex, comprising hundreds of overlapping patient journeys, and is a determinant of operational efficiency. To understand the network architecture of patient flow, we performed a data-driven network analysis of patient flow through two acute hospital sites of King’s College Hospital NHS Foundation Trust. Administration databases were queried for all intra-hospital patient transfers in an 18- month period and modelled as a dynamic weighted directed graph. A ‘core’ subnetwork containing only 13-17% of all edges channelled 83-90% of the patient flow, while an ‘ephemeral’ network constituted the remainder. Unsupervised cluster analysis and differential network analysis identified sub-networks where traffic is most associated with A&E performance the following day. Increased flow to clinical decision units was associated with the best A&E performance in both sites. The component analysis also detected a weekend effect on patient transfers which was not associated with performance. We have performed the first data-driven hypothesis-free analysis of patient flow which can enhance understanding of whole healthcare systems. Such analysis can drive transformation in healthcare as it has in industries such as manufacturing.
JfxNgs: A BAM/VCF viewer with javascript-based filtering/reformatting functionalities
Authors: Lindenbaum Pierre , Karakachoff Matilde , Redon Richard
Published: March 2017

Motivation

Visualizing BAM and VCF files is a common task for biologists, but they’re missing a way to filter and to explore the details of each short-read or variation.

Results

In that context, we wrote an interactive java-based interface namedJfxNgsthat uses javascript snippets to filter and reformat BAM and VCF files.

Availability

https://github.com/lindenb/jvarkit/blob/master/docs/JfxNgs.md

Contact

pierre.lindenbaum@univ-nantes.fr.