bluuebunny/crossref_metadata_2025 huggingface dataset:
National trends in safety performance of electronic health record systems in children’s hospitals
Authors: Chaparro Juan D , Classen David C , Danforth Melissa , Stockwell David C , Longhurst Christopher A
Published: September 2016

Objective: To evaluate the safety of computerized physician order entry (CPOE) and associated clinical decision support (CDS) systems in electronic health record (EHR) systems at pediatric inpatient facilities in the US using the Leapfrog Group’s pediatric CPOE evaluation tool.

Methods: The Leapfrog pediatric CPOE evaluation tool, a previously validated tool to assess the ability of a CPOE system to identify orders that could potentially lead to patient harm, was used to evaluate 41 pediatric hospitals over a 2-year period. Evaluation of the last available test for each institution was performed, assessing performance overall as well as by decision support category (eg, drug-drug, dosing limits). Longitudinal analysis of test performance was also carried out to assess the impact of testing and the overall trend of CPOE performance in pediatric hospitals.

Results: Pediatric CPOE systems were able to identify 62% of potential medication errors in the test scenarios, but ranged widely from 23–91% in the institutions tested. The highest scoring categories included drug-allergy interactions, dosing limits (both daily and cumulative), and inappropriate routes of administration. We found that hospitals with longer periods since their CPOE implementation did not have better scores upon initial testing, but after initial testing there was a consistent improvement in testing scores of 4 percentage points per year.

Conclusions: Pediatric computerized physician order entry (CPOE) systems on average are able to intercept a majority of potential medication errors, but vary widely among implementations. Prospective and repeated testing using the Leapfrog Group’s evaluation tool is associated with improved ability to intercept potential medication errors.
The stellar halo in the inner Milky Way: predicted shape and kinematics
Authors: Pérez-Villegas Angeles , Portail Matthieu , Gerhard Ortwin
Published: September 2016

We have used N-body simulations for the Milky Way to investigate the kinematic and structural properties of the old metal-poor stellar halo in the barred inner region of the Galaxy. We find that the extrapolation of the density distribution for bulge RR Lyrae stars, ρ ∼ r−3, approximately matches the number density of RR Lyrae in the nearby stellar halo. We follow the evolution of such a tracer population through the formation and evolution of the bar and box/peanut bulge in the N-body model. We find that its density distribution changes from oblate to triaxial, and that it acquires slow rotation in agreement with recent measurements. The maximum radial velocity is ∼15–25 km s−1 at |l| = 10°–30°, and the velocity dispersion is ∼120 km s−1. Even though the simulated metal-poor halo in the bulge has a barred shape, just 12 per cent of the orbits follow the bar, and it does not trace the peanut/X structure. With these properties, the RR Lyrae population in the Galactic bulge is consistent with being the inward extension of the Galactic metal-poor stellar halo.
A Systematic Review and Meta-Analysis of Migraine and Suicidal Ideation
Authors: Friedman Lauren E. , Gelaye Bizu , Bain Paul A. , Williams Michelle A.
Published: September 2016

Background:

Previous studies have demonstrated an association between migraine and major depressive disorder. However, relatively little is known about the relationship between suicidal ideation, with or without concurrent depression, and migraine.

Objective:

We conducted a systematic literature review to synthesize the available research focused on investigating the association of migraine with suicidal ideation.

Methods:

Relevant research papers were identified through searches of major electronic databases including PubMed, Embase (Elsevier), Web of Science (Thomson Reuters), PsycINFO (EBSCO), and Google Scholar. We performed a meta-analysis to estimate the pooled unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between migraine and suicidal ideation extracted from each study.

Results:

A total of 148,977 participants in 6 studies were included in this analysis. Overall, findings from available studies documented elevated odds of suicidal ideation among individuals with migraines. In unadjusted models, the odds of suicidal ideation was 2.49-fold higher among individuals with migraine (OR, 2.49; 95% CI, 2.34-2.65) compared with those without migraine. In multivariate-adjusted models, the pooled adjusted OR of suicidal ideation was 1.31 (OR, 1.31; 95% CI, 1.10-1.55).

Conclusions:

A meta-analysis of available studies suggests a modest positive association between migraine and suicidal ideation. Further studies allowing for a more comprehensive investigation of the association between migraine and the full range of suicidal behaviors are warranted. A larger and more robust evidence-base may be useful to inform the clinical screening and diagnoses of comorbid conditions in migraineurs.
Pain Sensitivity and its Relation to Spreading on the Body, Intensity, Frequency, and Duration of Pain
Authors: Larsson Britt , Gerdle Björn , Björk Jonas , Grimby-Ekman Anna
Published: September 2016

Objectives:

Individuals with chronic pain often report increased pain sensitivity compared with pain-free individuals; hence, it is crucial to determine whether and how different pain characteristics influence or interact with pain sensitivity. An alternative to experimental pain sensitivity testing is the self-reported pain sensitivity questionnaire (PSQ), which captures pain sensitivity in various body areas.

This study compares PSQ in individuals with and without pain and clarifies how pain sensitivity relates to spreading of pain on the body, and to intensity, frequency, duration of pain and to age and sex.

Materials and Methods:

A total of 5905 individuals with pain and 572 individuals without pain from the general population in southeastern Sweden completed and returned a postal questionnaire.

Results:

The mean PSQ score was 3.9 (95% confidence interval [CI], 3.88-3.98) in individuals with pain and 3.5 (95% CI, 3.38-3.64) in pain-free individuals. Hence, PSQ was the highest among individuals with pain, with a difference of 0.4 (95% CI, 0.30-0.56). There was a considerable variation in the PSQ values (mean=3.5; SD=1.54) among pain-free individuals. Pain sensitivity was positively related to spreading, intensity, and frequency of pain, with a correlation coefficient of 0.3. PSQ was higher in widespread pain, 4.5 (95% CI, 4.27-4.69) in women and 4.3 (95% CI, 3.94-4.71) in men, than in local pain, 3.7 (95% CI, 3.61-3.91) in women and 3.8 (95% CI, 3.66-3.95) in men. The score for women with regional pain was between local and widespread pain at 4.0 (95% CI, 3.95-4.11) and that for men with regional pain was 3.8 (95% CI, 3.69-3.87), which is equal to that of local pain.

Discussion:

The positive association between pain sensitivity and spreading of pain on the body provides some evidence that the extent of spreading may be related to the degree of pain sensitivity. Before clinical use of PSQ, psychometric development and further research are needed.
Psychological Predictors of Acute Postoperative Pain After Hysterectomy for Benign Causes
Authors: Scheel Jennifer , Sittl Reinhard , Griessinger Norbert , Strupf Marion , Parthum Andreas , Dimova Violeta , Horn-Hofmann Claudia , Thiel Falk , Beckmann Matthias W. , Lautenbacher Stefan
Published: September 2016

Objectives:

Psychological parameters have been shown to contribute significantly to the development of acute postoperative pain (APOP). For the prediction of APOP in chest malformation patients and cancer patients, we found pain-specific psychological predictors to be of higher relevance than general psychological predictors. The current study aims to further substantiate these findings.

Materials and Methods:

In a sample of 73 middle-aged hysterectomy patients, 3 predictor sets were assessed 1 day before surgery: attentional biases (toward pain-related, social threat, and positive words in a dot-probe task), pain-related emotions and cognitions (pain anxiety, pain catastrophizing, and pain hypervigilance), and affective state variables (depression and somatization). APOP intensity rated 2 to 3 days after surgery and analgesic consumption during the first 48 postoperative hours were used as outcome measures.

Results:

APOP intensity ratings were significantly explained by their best single predictors in a multiple regression analysis: social threat words of the dot-probe task, pain anxiety, and somatization (14.7% of explained variance). When comparing standardized β coefficients, pain-specific psychological predictors appeared to be of higher explanatory relevance than general psychological predictors. In contrast, analgesic consumption could not be significantly predicted by the psychological variables.

Discussion:

Hysterectomy patients at risk for high APOP intensity could be characterized by the psychological variables used, whereas their predictive value for analgesic consumption was limited. The high predictive potency of pain-specific psychological variables should be considered for further improvement of pain management and prevention, because pain-specific variables such as pain anxiety can be the target of focal psychological interventions when preparing for surgery.
The Ponseti technique and improved ankle dorsiflexion in children with relapsed clubfoot: a retrospective data analysis
Authors: Marquez Erika , Pacey Verity , Chivers Alison , Gibbons Paul , Gray Kelly
Published: September 2016

This study quantifies the change in passive ankle range of motion following modified Ponseti casting in children with relapsed idiopathic clubfoot. Fifty-three cases (feet) were retrospectively reviewed, with 6-month follow-up data available for 72% of participants. The median improvement in dorsiflexion was 15° (95% confidence interval: 12.5°–17.5°, P≤0.05), with 85% achieving dorsiflexion≥10°. At the 6-month follow-up, dorsiflexion remained significantly improved and 12 feet (32%) presented with subsequent relapse. Nine were referred for further casting and three were recommended for extra-articular surgery. Repeat modified Ponseti management clinically and statistically improves passive ankle dorsiflexion in relapsed idiopathic clubfoot.
ACR Appropriateness Criteria® Hodgkin Lymphoma-Favorable Prognosis Stage I and II
Authors: Dhakal Sughosh , Advani Ranjana , Ballas Leslie K. , Dabaja Bouthaina S. , Flowers Christopher R. , Ha Chul S. , Hoppe Bradford S. , Mendenhall Nancy P. , Metzger Monika L. , Plastaras John P. , Roberts Kenneth B. , Shapiro Ronald , Smith Sonali M. , Terezakis Stephanie A. , Winkfield Karen M. , Younes Anas , Constine Louis S.
Published: September 2016

This topic addresses the treatment of newly diagnosed patients with favorable prognosis stage I and II Hodgkin lymphoma. In most cases, combined modality therapy (chemotherapy followed by involved site radiation therapy) constitutes the current standard of care. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the appropriate use of combined modality therapy for favorable prognosis stage I and II Hodgkin lymphoma. Increasing information about the late effects of treatment has led to attempts to decrease toxicity by using less chemotherapy (decreased duration and/or intensity or different agents) and less radiation therapy (reduced volume and/or dose) while maintaining excellent efficacy.
Mechanical Stimulation Increases Knee Meniscus Gene RNA-level Expression in Adipose-derived Stromal Cells
Authors: Meier Elizabeth M. , Wu Bin , Siddiqui Aamir , Tepper Donna G. , Longaker Michael T. , Lam Mai T.
Published: September 2016

Background:

Efforts have been made to engineer knee meniscus tissue for injury repair, yet most attempts have been unsuccessful. Creating a cell source that resembles the complex, heterogeneous phenotype of the meniscus cell remains difficult. Stem cell differentiation has been investigated, mainly using bone marrow mesenchymal cells and biochemical means for differentiation, resulting in no solution. Mechanical stimulation has been investigated to an extent with no conclusion. Here, we explore the potential for and effectiveness of mechanical stimulation to induce the meniscal phenotype in adipose-derived stromal cells.

Methods:

Human adipose-derived stromal cells were chosen for their fibrogenic nature and conduciveness for chondrogenesis. Biochemical and mechanical stimulation were investigated. Biochemical stimulation included fibrogenic and chondrogenic media. For mechanical stimulation, a custom-built device was used to apply constant, cyclical, uniaxial strain for up to 6 hours. Strain and frequency varied.

Results:

Under biochemical stimulation, both fibrogenic (collagen I, versican) and chondrogenic (collagen II, Sox9, aggrecan) genes were expressed by cells exposed to either fibrogenic or chondrogenic biochemical factors. Mechanical strain was found to preferentially promote fibrogenesis over chondrogenesis, confirming that tensile strain is an effective fibrogenic cue. Three hours at 10% strain and 1 Hz in chondrogenic media resulted in the highest expression of fibrochondrogenic genes. Although mechanical stimulation did not seem to affect protein level expression, biochemical means did affect protein level presence of collagen fibers.

Conclusion:

Mechanical stimulation can be a useful differentiation tool for mechanoresponsive cell types as long as biochemical factors are also integrated.
A Unique Case of Allogeneic Fat Grafting Between Brothers
Authors: Kim Samuel , Edelson Richard L. , Sumpio Brandon , Kwei Stephanie , Narayan Deepak
Published: September 2016

We present a case of a 65-year-old man with cutaneous T-cell lymphoma treated with radiation therapy and an allogeneic hematopoietic stem cell transplant from his human leukocyte antigen-matched brother. Engraftment was successful, but the patient went on to develop painful, radiation-induced ulcers. The ulcers were fat-allografted using liposuctioned fat from his brother because of the patient’s unique chimeric state. Postprocedure follow-up revealed epithelialization of the ulcer sites and significant improvement in neuropathic pain. Our unique case study supports the use of fat grafting for its restorative purposes and for its ability to alleviate chronic neuropathic pain. Additionally, it appears that our case provides a basis of a general approach to the treatment of radiation-induced ulcers in chimeric patients with lymphoid malignancies.
Right Minithoracotomy Approach for Replacement of the Ascending Aorta, Hemiarch, and Aortic Valve
Authors: Lamelas Joseph , LaPietra Angelo
Published: September 2016

A minimally invasive right anterior thoracotomy approach is the preferred technique used at our institution for isolated aortic valve pathology. We have recently introduced more complex concomitant minimally invasive procedures through this access site. Here, we describe how we perform a replacement of the ascending aorta and aortic valve with and without the use of circulatory arrest through a 6-cm right minimally invasive thoracotomy incision.
The impact of peripheral nerve blocks on perioperative outcome in hip and knee arthroplasty—a population-based study
Authors: Memtsoudis Stavros G. , Poeran Jashvant , Cozowicz Crispiana , Zubizarreta Nicole , Ozbek Umut , Mazumdar Madhu
Published: September 2016

The role of anesthesia techniques on perioperative outcomes on a population level has recently gained widespread interest. Although mainly neuraxial vs general anesthesia has been addressed, population-level data on the impact of peripheral nerve blocks (PNBs) are still lacking. Therefore, we investigated the association between PNB use and outcomes using retrospective data on 1,062,152 recipients of hip and knee arthroplasties (total hip arthroplasty [THA]/total knee arthroplasty [TKA]) from the national Premier Perspective database (2006-2013). Multilevel multivariable logistic regression models measured associations between PNB use and outcomes. Complications included cardiac, pulmonary, gastrointestinal and renal complications, cerebrovascular events, infections, wound complications, thromboembolic complications, inpatient falls, and mortality. Resource utilization variables included blood transfusions, intensive care unit admissions, opioid consumption, cost, and length of stay. Overall, 12.5% of patients received a PNB, with an increase over time particularly among TKAs. Peripheral nerve block use was associated with lower odds for most adverse outcomes mainly among patients with THA. Notable beneficial effects were seen for wound complications (odds ratio 0.60 [95% confidence interval, 0.49-0.74]) among THA recipients and pulmonary complications (odds ratio 0.83 [95% confidence interval, 0.72-0.94]) in patients with TKA. Peripheral nerve block use was significantly (P < 0.0001) associated with a −16.2% and −12.7% reduction in opioid consumption for patients with THA and TKA, respectively. In conclusion, our results indicate that PNBs might be associated with superior perioperative population-level outcomes. In light of the inability to establish a causal relationship and the presence of residual confounding, we strongly advocate for further prospective investigation, ideally in multicenter, randomized trials, to establish the potential impact of PNBs on outcomes on a population level.
Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study
Authors: Wodarski Rachel , Delaney Ada , Ultenius Camilla , Morland Rosie , Andrews Nick , Baastrup Catherine , Bryden Luke A. , Caspani Ombretta , Christoph Thomas , Gardiner Natalie J. , Huang Wenlong , Kennedy Jeffrey D. , Koyama Suguru , Li Dominic , Ligocki Marcin , Lindsten Annika , Machin Ian , Pekcec Anton , Robens Angela , Rotariu Sanziana M. , Voß Sabrina , Segerdahl Marta , Stenfors Carina , Svensson Camilla I. , Treede Rolf-Detlef , Uto Katsuhiro , Yamamoto Kazumi , Rutten Kris , Rice Andrew S.C.
Published: September 2016

Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.
Chemical Analysis of Water Treatment in Sudan
Authors: Mostafa Sojoud H. , Hamza Alnazier O. , Khider Mohamed O.
Published: September 2016

Dialysis machines are artificial kidneys that perform some kidney functions for patients who have renal failure and are used to clean the blood and balance its constituents. The machine maintenance and calibration are extremely important in the evaluation of adequacy of hemodialysis and in assessing dialysis session performance. The objectives of this study are to change the degree of concentration of chemical elements in water treatment during a year time in the Kassala state, to decrease the risk of water contamination with respect to the kidney failure of patients in water treatment unit, and to find the best effective solutions in case of any changes in the chemical concentration of the water. The study has been done during the period from January 2014 to March 2015 in Kassala Hospital’s Department of Renal Diseases. The study author concluded that water element concentration rates changed significantly during the year. This conclusion requires an attention to investigate the reasons behind these changes and the effects of these changes on the dialysis treatments. One way to do so is to monitor the contents of water treatment unit periodically and to make sure that each part is efficiently working. This will be done by taking samples to check it regularly for accuracy, corresponding to the required needs.
Hepatitis B virus infection and risk of gallstones: a systematic review and meta-analysis
Authors: Wijarnpreecha Karn , Thongprayoon Charat , Panjawatanan Panadeekarn , Manatsathit Wuttiporn , Ungprasert Patompong
Published: September 2016

Background/objectives

Gallstone disease and its complications are common, particularly in Western populations. Recent studies have reported a significantly increased risk of gallstones among hepatitis C virus-infected patients. However, the data on patients with hepatitis B virus (HBV) infection are still limited. This meta-analysis was carried out with the aim of summarizing all available evidence.

Patients and methods

A literature search was performed using MEDLINE and the EMBASE database from inception to May 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of gallstones among HBV-infected patients versus patients without HBV infection were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse-variance method.

Results

Nine studies fulfilled our eligibility criteria and were included in the analysis. We found no significant association between HBV infection and the risk of gallstones, with a pooled OR of 1.10 (95% CI, 0.91–1.33). The statistical heterogeneity was moderate, with an I
2 of 69%. Subgroup analysis was carried out. The pooled OR of cross-sectional studies was 1.01 (95% CI, 0.91–1.12; I
2 0%), whereas the pooled OR of case–control studies was 1.53 (95% CI, 0.85–2.74; I
2 80%).

Conclusion

A significant association between HBV infection and the risk of gallstones was not observed in this study.
Composite Serous Borderline Tumor and Adult Granulosa Cell Tumor–like Area: Is it a True Neoplastic AGCT or Tumor-like Proliferation?
Authors: Yu Jun , Nie Xiu
Published: September 2016

We report the 402C-G FOXL2 mutation status in 1 epithelial ovarian lesion in a 38-yr-old woman showing stromal proliferations that were morphologically indistinguishable from adult granulosa cell tumor (AGCT). The lesion was a serous borderline tumor. The AGCT-like components were distributed within the septa and cyst walls. FOXL2 mutation was absent. The combination of an epithelial neoplasm and AGCT-like areas is rare but described. The AGCT-like components are likely to be tumor-like proliferations but not truly neoplastic AGCT. FOXL2 mutation testing may be useful in confirming an AGCT-like component.
A novel lozenge containing bupivacaine as topical alleviation of oral mucositis pain in patients with head and neck cancer: a pilot study
Authors: Mogensen Stine , Treldal Charlotte , Sveinsdottir Kolbrún , Jensen Kenneth , Kristensen Claus A. , Mogensen Torben S. , Petersen Janne , Andersen Ove
Published: September 2016

Introduction: Oral mucositis induces severe oral pain in head and neck cancer patients. There is at this point no effective pain treatment without considerable side effects.

Objective: The aim of this pilot study was to investigate pain reduction in oral cavity and pharynx in patients with head and neck cancer (HNC) with oral mucositis, the location of anesthetic effect, and duration of pain relief, after a single-dose administration of a 25 mg bupivacaine lozenge.

Methods: Ten patients with HNC suffering from oral mucositis pain were included. The patients assessed pain in the oral cavity and pharynx on a visual analogue scale (from 0 to 100 mm) at baseline and up to 3 hours after the lozenge was dissolved. Possible adverse events were registered.

Results: The baseline pain was 51 mm (range: 30–73 mm) in the oral cavity and 58 mm (range: 35–70 mm) in the pharynx. When the lozenge was dissolved, both oral (−27 mm; range: −3 to −52 mm; P = 0.0003) and pharynx pain (−20 mm; range: −3 to −45 mm; P = 0.008) were significantly reduced. After 180 minutes, the mean reduction in pain was significant in the oral cavity (−18 mm; range: −8 to −30 mm; P < 0.0001) but not in the pharynx (−8 mm; range: +4 to −23 mm; P = 0.12). No adverse events were observed.

Conclusion: The results indicate that the bupivacaine lozenge has a clinically significant and long-lasting pain-relieving effect on pain because of oral mucositis in patients with HNC.
Medical Students Raising Concerns
Authors: Druce Maralyn R. , Hickey Andrea , Warrens Anthony N. , Westwood Olwyn M.R.
Published: September 2016

After a number of high-profile incidents and national reports, it has become clear that all health professionals and all medical students must be able to raise concerns about a colleague’s behavior if this behavior puts patients, colleagues, or themselves at risk.

Detailed evidence from medical students about their confidence to raise concerns is limited, together with examples of barriers, which impair their ability to do so. We describe a questionnaire survey of medical students in a single-center, examining self-reported confidence about raising concerns in a number of possible scenarios. Thematic analysis was applied to comments about barriers identified.

Although 80% of respondents felt confident to report a patient safety issue, students were less confident around issues of probity, attitude, and conduct. This needs to be addressed to create clear mechanisms to raise concerns, as well as support for students during the process.
Cerebellar Control of Eye Movements
Authors: Beh Shin C. , Frohman Teresa C. , Frohman Elliot M.
Published: September 2016

Background:

The cerebellum plays a central role in the online, real-time control, and long-term modulation of eye movements.

Evidence acquisition:

We reviewed the latest (fifth) edition of Leigh and Zee's textbook, The Neurology of Eye Movements, and literature in PUBMED using the following terms: cerebellum, flocculus, paraflocculus, vermis, oculomotor vermis, dorsal vermis, caudal fastigial nucleus, fastigial oculomotor region, uvula, nodulus, ansiform lobule, eye movements, saccades, ipsipulsion, contrapulsion, smooth pursuit, vergence, convergence, divergence, gaze-holding, down beat nystagmus, vestibulo-ocular reflex (VOR), angular VOR, translational VOR, skew deviation, velocity storage.

Results:

The cerebellum is vital in optimizing the performance of all classes of gaze-shifting and gaze-stabilizing reflexes. The flocculus-paraflocculus are crucial to VOR gain and direction, pulse-step matching for saccades, pursuit gain, and gaze-holding. The ocular motor vermis and caudal fastigial nuclei are essential in saccadic adaptation and accuracy, and pursuit gain. The nodulus and ventral uvula are involved in processing otolothic signals and VOR responses, including velocity storage.

Conclusions:

The cerebellum guarantees the precision of ocular movements to optimize visual performance and occupies a central role in all classes of eye movements both in real-time control and in long-term calibration and learning (i.e., adaptation).
Synaesthesia lost and found: Two cases of person- and music-colour synaesthesia
Authors: Farina Francesca R , Mitchell Kevin J , Roche Richard AP
Published: September 2016

Synaesthesia is a developmental condition involving cross-communication between sensory modalities or substreams whereby an inducer (e.g. a sound) automatically evokes a concurrent percept in another modality (e.g. a colour). Whether this condition arises due to atypical structural connectivity (e.g., between normally unconnected cortical areas) or altered neurochemistry remains a central question. We report the exceptional cases of two synaesthetes – subjects AB and CD – both of whom experience coloured auras around individuals, as well as coloured perceptions in response to music. Both subjects have, in recent years, suffered a complete loss or reduction of their synaesthetic experiences, one (AB) through successive head traumas, including a lightning strike, followed by a number of medications, and the other (CD) while taking anxiolytic medications. Using semi-structured interviews and data from the Synaesthesia Battery and a colourpicker task, we characterise the phenomenological characteristics of their pre-loss synaesthesia, as well as the subsequent restoration of each subject's synaesthetic experiences (in the months post-trauma for AB, and after cessation of medication for CD). Even after years of suppression, the patterns of associations were highly consistent with those experienced pre-injury. The phenomenological experience of synaesthesia can, thus, like most conscious experiences, be modulated by pharmacologically diverse medications or head injury. However, the underlying neural substrates mediating specific synaesthetic pairings appear remarkably “hard-wired” and can persist over very long periods even under conditions that alter or completely suppress the conscious synaesthetic experience itself.
Enhancing pre-defined workflows withad hocanalytics using Galaxy, Docker and Jupyter
Authors: Grüning Björn A. , Rasche Eric , Rebolledo-Jaramillo Boris , Eberhard Carl , Houwaart Torsten , Chilton John , Coraor Nate , Backofen Rolf , Taylor James , Nekrutenko Anton
Published: September 2016

What does it take to convert a heap of sequencing data into a publishable result? First, common tools are employed to reduce primary data (sequencing reads) to a form suitable for further analyses (i.e., list of variable sites). The subsequent exploratory stage is much moread hocand requires development of custom scripts making it problematic for biomedical researchers. Here we describe a hybrid platform combining common analysis pathways with exploratory environments. It aims at fully encompassing and simplifying the “raw data-to-publication” pathway and making it reproducible.
State-dependent modulation of functional connectivity in early blind individuals
Authors: Pelland Maxime , Orban Pierre , Dansereau Christian , Lepore Franco , Bellec Pierre , Collignon Olivier
Published: September 2016

Resting-state functional connectivity (RSFC) studies have highlighted how visual experience influences the brain’s functional architecture. Reduced RSFC coupling between occipital (visual) and temporal (auditory) regions has been reliably observed in early blind individuals (EB) at rest. In contrast, task-dependent activation studies have repeatedly demonstrated enhanced co-activation and connectivity of occipital and temporal regions during auditory processing in EB. To investigate this apparent discrepancy, the functional coupling between temporal and occipital networks at rest was directly compared to that of an auditory task in both EB and sighted controls (SC). Functional brain clusters shared across groups and cognitive states (rest and auditory task) were defined. In EBs, we observed higher occipito-temporal correlations in activity during the task than at rest. The reverse pattern was observed in SC. We also observed higher temporal variability of occipito-temporal RSFC in EB suggesting that occipital regions in this population may play a role of multiple demand system. Our study reveals how the connectivity profile of sighted and early blind people is differentially influenced by their cognitive state, bridging the gap between previous task-dependent and RSFC studies. Our results also highlight how inferring group-differences in functional brain architecture solely based on resting-state acquisition has to be considered with caution.

Highlights

Occipito-temporal functional connectivity is modified by cognitive states.

This modulation is different in blind and sighted individuals.

Blind participants have higher occipito-temporal temporal variability at rest.

The group difference in variability at rest explains the differences in modulation.

Inferring group differences with resting-state data should be subject to caution.
Estimating the Selective Effect of Heterozygous Protein Truncating Variants from Human Exome Data
Authors: Cassa Christopher A. , Weghorn Donate , Balick Daniel J. , Jordan Daniel M. , Nusinow David , Samocha Kaitlin E. , O'Donnell Luria Anne , MacArthur Daniel G. , Daly Mark J. , Beier David R. , Sunyaev Shamil R.
Published: September 2016

The dispensability of individual genes for viability has interested generations of geneticists. For some genes it is essential to maintain two functional chromosomal copies, while other genes may tolerate the loss of one or both copies. Exome sequence data from 60,706 individuals provide sufficient observations of rare protein truncating variants (PTVs) to make genome-wide estimates of selection against heterozygous loss of gene function. The cumulative frequency of rare deleterious PTVs is primarily determined by the balance between incoming mutations and purifying selection rather than genetic drift. This enables the estimation of the genome-wide distribution of selection coefficients for heterozygous PTVs and corresponding Bayesian estimates for individual genes. The strength of selection can help discriminate the severity, age of onset, and mode of inheritance in Mendelian exome sequencing cases. We find that genes under the strongest selection are enriched in embryonic lethal mouse knockouts, putatively cell-essential genes inferred from human tumor cells, Mendelian disease genes, and regulators of transcription. Using an essentiality screen, we find a large set of genes under strong selection that are likely to have critical function but that have not yet been studied extensively.
Single variant bottleneck in the early dynamics ofH. influenzaebacteremia in neonatal rats questions the theory of independent action
Authors: Shao Xinxian , Levin Bruce , Nemenman Ilya
Published: September 2016

There is an abundance of information about the genetic basis, physiological and molecular mechanisms of bacterial pathogenesis. In contrast, relatively little is known about population dynamic processes, by which bacteria colonize hosts and invade tissues and cells and thereby cause disease. In an article published in 1978, Moxon and Murphy presented evidence that, when inoculated intranasally with a mixture streptomycin sensitive and resistant (SmSand SmR) and otherwise isogenic stains ofHaemophilus influenzaetype b (Hib), neonatal rats develop a bacteremic infection that often is dominated by only one strain, SmSor SmR. After rulling out other possibilities through years of related experiments, the field seems to have settled on a plausible explanation for this phenomenon: the first bacterium to invade the host activates the host immune response that ‘shuts the door’ on the second invading strain. To explore this hypothesis in a necessarily quantitative way, we modeled this process with a set of mixed stochastic and deterministic differential equations. Our analysis of the properties of this model with realistic parameters suggests that this hypothesis cannot explain the experimental results of Moxon and Murphy, and in particular the observed relationship between the frequency of different types of blood infections (bacteremias) and the inoculum size. We propose modifications to the model that come closer to explaining these data. However, the modified and better fitting model contradicts the common theory of independent action of individual bacteria in establishing infections. We discuss the implications of these results.
Length control of filamentous structures in cells by the limiting pool mechanism
Authors: Mohapatra Lishibanya , Lagny Thibaut J. , Harbage David , Jelenkovic Predrag R. , Kondev Jane
Published: September 2016

How the size of organelles in cells is controlled despite a constant turnover of their constituent parts is a central problem in cell biology. A general mechanism has been proposed based on the idea that an organelle grows by self-assembly of molecular subunits that freely diffuse in the cytoplasm. Assembly continues until the available pool of subunits is depleted to the point when the stochastic addition and removal of subunits is balanced, leading to a structure of well-defined size. Here we focus on length control of multiple filamentous structures in cells, such as actin cables and flagella. Using queueing theory and computation we show that the limiting pool mechanism leads to three different phases of assembly, starting with a rapid growth phase when all filaments quickly accumulate a large number of available subunits. Then, the slower growing filamentous structures enter a disassembly phase as they gradually lose all of their subunits to the faster growing structures. Finally, when multiple, equivalent fast-growing filaments are present, their lengths undergo protracted diffusive dynamics due to the stochastic swapping of subunits between them. This eventually leads to a broad, power-law distribution of filament lengths in steady state. Our findings demonstrate that the limiting-pool mechanism is incapable of controlling lengths of multiple filamentous structures that are assembled from a common pool of subunits, and at best, can produce only one filament of a well-defined size. Overall, our theoretical results reveal physical limitations of the limiting-pool mechanism of organelle size control.

Significance Statement

What determines the size of organelles in cells is a classic problem in cell biology. Recent experiments on mitotic spindles, and nucleolus have singled out the limiting-pool mechanism of size control. As these structures assemble, they deplete a finite pool of subunits present in the cell, thereby reducing the rate of subunit addition. Eventually the stochastic addition and removal of subunits are balanced and a well-defined size is achieved. We find that, while the limiting-pool mechanism does control the size of an individual structure, it fails when multiple structures are competing for the same pool of subunits. In that case we predict large size fluctuations and that the fastest growing structure takes up practically all the subunits from the pool.
Bursting deep dorsal horn neurons: the pharmacological target for the anti-spastic effects of Zolmitriptan?
Authors: Carlsen Eva Meier , Rasmussen Rune
Published: September 2016

In a recent publication, Thaweerattanasinp and colleagues employed an in vitro preparation and electrophysiology to investigate firing properties of deep dorsal horn neurons following spinal cord injury during NMDA or zolmitriptan application. Deep dorsal horn neurons were classified into bursting, simple or tonic, with bursting neurons showing NMDA and zolmitriptan sensitivity. Here, we discuss the findings in a methodological framework and propose future experiments of importance for translating the results into a physiological setting.
Assessing Prediction Performance of Neoadjuvant Chemotherapy Response in Bladder Cancer
Authors: Cremer Chris
Published: September 2016

Neoadjuvant chemotherapy is a treatment routinely prescribed to patients diagnosed with muscle-invasive bladder cancer. Unfortunately, not all patients are responsive to this treatment and would greatly benefit from an accurate prediction of their expected response to chemotherapy. In this project, I attempt to develop a model that will predict response using tumour microarray data. I show that using my dataset, every method is insufficient at accurately classifying responders and non-responders.
Hazardous Alcohol Use Associated with Increased Sexual Risk Behaviors Among People Who Inject Drugs
Authors: Fairbairn Nadia , Hayashi Kanna , Milloy M‐J , Nolan Seonaid , Nguyen Paul , Wood Evan , Kerr Thomas
Published: September 2016

Background

Alcohol is associated with a multitude of severe health consequences. While risk behaviors related to illicit drug use are commonly studied among people who inject drugs (PWID), the role of alcohol use has received substantially less attention in this population. We explored whether drug and sexual risk behaviors as well as experiences of violence were associated with hazardous alcohol use in a cohort of PWID.

Methods

Analyses were conducted using observational data from a prospective cohort of community‐recruited HIV‐negative PWID in Vancouver, Canada. We used the U.S. National Institute on Alcohol Abuse and Alcoholism definition of hazardous alcohol use (i.e., >14 drinks/wk or >4 drinks on 1 occasion for men, and >7 drinks/wk or >3 drinks on 1 occasion for women). We used multivariable generalized estimating equations (GEE) to identify the factors associated with hazardous alcohol use.

Results

Between 2006 and 2012, 1,114 HIV‐negative individuals were recruited, and 186 (16.7%) reported hazardous alcohol use in the previous 6 months at baseline. In multivariable GEE analyses, having multiple sex partners (adjusted odds ratio [AOR] = 1.25), history of sexually transmitted infection (AOR = 1.50), experiencing violence (AOR = 1.36), and incarceration (AOR = 1.29) were each independently associated with hazardous alcohol use. Caucasian ethnicity (AOR = 0.56), ≥ daily heroin injection (AOR = 0.81), and engagement in addiction treatment (AOR = 0.84) were negatively associated with hazardous alcohol use (all p < 0.05).

Conclusions

A considerable proportion of PWID reported hazardous alcohol use, which was independently associated with reporting sexual, but not drug‐related, HIV risk behaviors and experiencing recent violence. Findings suggest a need to integrate regular screening and evidence‐based alcohol interventions into treatment efforts for PWID.
Identifying women at risk for postpartum anxiety: a prospective population‐based study
Authors: Dennis C.‐L. , Falah‐Hassani K. , Brown H. K. , Vigod S. N.
Published: September 2016

Objective

To develop a multifactorial model to predict anxiety symptomatology at 8 weeks postpartum.

Method

In a population‐based study, 522 women in a health region near Vancouver, Canada, completed questionnaires at 1, 4, and 8 weeks postpartum. Questionnaires included risk factors measured at 1 week (sociodemographic, biological, pregnancy‐related, life stressors, social support, obstetric, and maternal adjustment). Sequential logistic regression was completed to develop a predictive model of anxiety symptomatology at 8 weeks (State‐Trait Anxiety Inventory score >40).

Results

The prevalence of anxiety symptomatology at 1, 4, and 8 weeks postpartum was 22.6%, 17.2%, and 14.8% respectively. In multivariable models, anxiety symptomatology at 1 week (aOR 2.78, 95% CI: 1.04–7.43), multiparous parity (aOR 3.29, 95% CI: 1.28–8.48), history of psychiatric problems (aOR 3.07, 95% CI: 1.19–7.97), perceived stress (1 SD increase: aOR 4.92, 95% CI: 2.62–9.26), and childcare stress (1 SD increase: aOR 1.63, 95% CI: 1.01–2.64) were independent predictors of anxiety symptomatology at 8 weeks.

Conclusion

While a significant proportion of women experience anxiety symptomatology following childbirth, multiparous women with a psychiatric history who have high levels of diverse stress are at greatest risk. These key factors may be used to promote early identification and secondary preventive interventions.
Cervical length at 11–40 weeks: unconditional and conditional longitudinal reference ranges
Authors: Papastefanou Ioannis , Pilalis Athanasios , Kappou Dimitra , Souka Athena P.
Published: September 2016

Introduction

Our aim was to establish unconditional and conditional longitudinal reference ranges for cervical length throughout pregnancy.

Material and methods

Prospective longitudinal study. In singleton pregnancies repeated cervical length measurements were carried out by transvaginal ultrasound throughout gestation. Multilevel modeling was applied to establish cervical length reference ranges from 11 to 40 weeks.

Results

In all, 4397 women contributed to 13 765 cervical length measurements. A linear mixed effects random intercept–random slope model was fitted to the data. Mean cervical length had a negative non‐linear polynomial association with gestational age. Unconditional ranges were developed. Terms that allow the construction of personalized cervical length charts conditional to a previous measurement were calculated.

Conclusions

We constructed longitudinal reference charts for cervical length in singleton pregnancies. Cervical length should be adjusted according to specific gestational‐age‐dependent ranges. Individualization of cervical assessment is feasible by the application of charts conditional to previous measurements.
Reporting on data monitoring committees in neonatal randomised controlled trials is inconsistent
Authors: Perrem LM , Gosling S , Ravikumar I , Khashan AS , Miletin J , Ryan CA , Dempsey E
Published: September 2016

Aim

To evaluate the reported use of data monitoring committees (DMCs), the frequency of interim analysis, prespecified stopping rules and early trial termination in neonatal randomised controlled trials (RCTs).

Methods

We reviewed neonatal RCTs published in four high‐impact general medical journals, specifically looking at safety issues including documented involvement of a DMC, stated interim analysis, stopping rules and early trial termination. We searched all journal issues over an 11‐year period (2003–2013) and recorded predefined parameters on each item for RCTs meeting inclusion criteria.

Results

Seventy neonatal trials were identified in four general medical journals: Lancet, New England Journal of Medicine (NEJM), British Medical Journal and Journal of American Medical Association. A total of 43 (61.4%) studies reported the presence of a DMC, 36 (51.4%) explicitly mentioned interim analysis, stopping rules were reported in 15 (21.4%) RCTs and seven (10%) trials were terminated early. The NEJM most frequently reported these parameters compared to the other three journals reviewed.

Conclusion

While the majority of neonatal RCTs report on DMC involvement and interim analysis, there is still scope for improvement. Clear documentation of safety‐related issues should be a central component of reporting in neonatal trials involving newborn infants.