bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and Associated Risk Factors of Traumatic Brain Injury in a Cohort of Homeless and Vulnerably Housed Adults in 3 Canadian Cities
Authors: Nikoo Mohammadali , Gadermann Anne , To Matthew J. , Krausz Michael , Hwang Stephen W. , Palepu Anita
Published: November 2016

Objective:

To examine the factors associated with incident traumatic brain injury (TBI) among homeless and vulnerably housed persons over a 3-year follow-up period.

Setting and participants:

Data were obtained from the Health and Housing in Transition study, which tracked the health and housing status of 1190 homeless or vulnerably housed individuals in 3 Canadian cities for 3 years.

Design and Main Measures:

Main measure was self-reported incident TBI during the follow-up period. Factors associated with TBI were ascertained using mixed-effects logistic regression.

Results:

During first, second, and third years of follow-up, 187 (19.4%), 166 (17.1%), and 172 (17.9%) participants reported a minimum of 1 incident TBI, respectively. Among 825 participants with available data for all 3 years of follow-up, 307 (37.2%) reported at least 1 incident TBI during the 3-year follow-up period. Lifetime prevalence of TBI, endorsing a history of mental health diagnoses at baseline, problematic alcohol and drug use, younger age, poorer mental health, and residential instability were associated with increased risk of incident TBI during follow-up period.

Conclusion:

Mental health support and addressing residential instability and problematic substance use may reduce further risk of TBI and its associated poor health and social outcomes in this population.
The Minimal Clinically Important Difference for the Mayo-Portland Adaptability Inventory
Authors: Malec James F. , Kean Jacob , Monahan Patrick O.
Published: November 2016

Objectives:

To determine the Minimal Clinically Important Difference (MCID) and Robust Clinically Important Difference (RCID) of the Mayo-Portland Adaptability Inventory–4 (MPAI-4) as measures of response to intervention.

Methods:

Retrospective analysis of existing data. Both distribution- and anchor-based methods were used to triangulate on the MCID and to identify a moderate, that is, more robust, level of change (RCID) for the MPAI-4. These were further evaluated with respect to clinical provider ratings.

Participants:

Data for individuals with acquired brain injury in rehabilitation programs throughout the United States in the OutcomeInfo Database (n = 3087) with 2 MPAI-4 ratings.

Main Measures:

MPAI-4, Supervision Rating Scale, Clinician Rating of Global Clinical Improvement.

Results:

Initial analyses suggested 5 T-score points (5T) as the MCID and 9T as the RCID. Eighty-one percent to 87% of clinical raters considered a 5T change and 99% considered a 9T change to indicate meaningful improvement.

Conclusions:

5T represents the MCID for the MPAI-4 and 9T, the RCID. Both values are notably less than the Reliable Change Index (RCI). While the RCI indicates change with a high level of statistical confidence, it may be insensitive to change that is considered meaningful by providers and participants as indicated by the MCID.
Factors Associated With Rehabilitation Outcomes After Traumatic Brain Injury: Comparing Functional Outcomes Between TBIMS Centers Using Hierarchical Linear Modeling
Authors: Dahdah Marie N. , Hofmann Melissa , Pretz Christopher , An Viktoriya , Barnes Sunni A. , Bennett Monica , Dreer Laura E. , Bergquist Thomas , Shafi Shahid
Published: November 2016

Objective:

To examine differences in patient outcomes across Traumatic Brain Injury Model Systems (TBIMS) rehabilitation centers and factors that influence these differences using hierarchical linear modeling (HLM).

Setting:

Sixteen TBIMS centers.

Participants:

A total of 2056 individuals 16 years or older with moderate to severe traumatic brain injury (TBI) who received inpatient rehabilitation.

Design:

Multicenter observational cohort study using HLM to analyze prospectively collected data.

Main Outcome Measures:

Functional Independence Measure and Disability Rating Scale total scores at discharge and 1 year post-TBI.

Results:

Duration of posttraumatic amnesia (PTA) demonstrated a significant inverse relationship with functional outcomes. However, the magnitude of this relationship (change in functional status for each additional day in PTA) varied among centers. Functional status at discharge from rehabilitation and at 1 year post-TBI could be predicted using the slope and intercept of each TBIMS center for the duration of PTA, by comparing it against the average slope and intercept.

Conclusions:

HLM demonstrated center effect due to variability in the relationship between PTA and functional outcomes of patients. This variability is not accounted for in traditional linear regression modeling. Future studies examining variations in patient outcomes between centers should utilize HLM to measure the impact of additional factors that influence patient rehabilitation functional outcomes.
USE OF A CARBONIC ANHYDRASE INHIBITOR IN X-LINKED RETINOSCHISIS
Authors: Andreuzzi Paola , Fishman Gerald A. , Anderson Robert J.
Published: November 2016

Purpose:

To evaluate changes in cystic-appearing macular lesions and visual acuity in patients with X-linked retinoschisis while being treated with a carbonic anhydrase inhibitor.

Methods:

A retrospective analysis of 68 eyes from 36 patients between the ages of 5 years and 61 years with X-linked retinoschisis were monitored while on a carbonic anhydrase inhibitor. Macular cystic-appearing lesions were monitored with optical coherence tomography. Snellen visual acuity measurements were converted to logarithm of the minimum angle of resolution equivalent Early Treatment Diabetic Retinopathy Study letters for analysis. Analyses for changes in both visual acuity and macular cysts included comparisons between treatment and pretreatment segments.

Results:

Forty-five eyes (66%) had a reduction of their cysts while on a carbonic anhydrase inhibitor. Twenty eyes (29%) showed no cystic change, whereas 3 eyes (4%) demonstrated worsening of their cysts with treatment when compared with pretreatment. There was a statistically significant improvement in logarithm of the minimum angle of resolution visual acuity while on treatment relative to pretreatment (P < 0.0001). The estimated average Early Treatment Diabetic Retinopathy Study equivalent improvement was 0.09 (slightly less than one line on the Early Treatment Diabetic Retinopathy Study chart) with a 95% confidence interval of 0.08 to 0.11.

Conclusion:

Considering the entire 36 patients in this cohort, while statistically significant, the average improvement in visual acuity was modest. Nonetheless, in individual patients, the improvement was more substantial. Improvement in the extent of cystic macular lesions was observed in a high percentage of cases.
CLINICAL PRESENTATION AND DISEASE COURSE OF USHER SYNDROME BECAUSE OF MUTATIONS IN MYO7A OR USH2A
Authors: Testa Francesco , Melillo Paolo , Bonnet Crystel , Marcelli Vincenzo , de Benedictis Antonella , Colucci Raffaella , Gallo Beatrice , Kurtenbach Anne , Rossi Settimio , Marciano Elio , Auricchio Alberto , Petit Christine , Zrenner Eberhart , Simonelli Francesca
Published: November 2016

Purpose:

To evaluate differences in the visual phenotype and natural history of Usher syndrome caused by mutations in MYO7A or USH2A, the most commonly affected genes of Usher syndrome Type I (USH1) and Type II (USH2), respectively.

Methods:

Eighty-eight patients with a clinical diagnosis of USH1 (26 patients) or USH2 (62 patients) were retrospectively evaluated. Of these, 48 patients had 2 disease-causing mutations in MYO7A (10 USH1 patients), USH2A (33 USH2 patients), and other USH (5 patients) genes. Clinical investigation included best-corrected visual acuity, Goldmann visual field, fundus photography, electroretinography, and audiologic and vestibular assessments. Longitudinal analysis was performed over a median follow-up time of 3.5 years.

Results:

Patients carrying mutations in MYO7A had a younger age of onset of hearing and visual impairments than those carrying mutations in USH2A, leading to an earlier diagnosis of the disease in the former patients. Longitudinal analysis showed that visual acuity and visual field decreased more rapidly in subjects carrying MYO7A mutations than in those carrying USH2A mutations (mean annual exponential rates of decline of 3.92 vs. 3.44% and of 8.52 vs. 4.97%, respectively), and the former patients reached legal blindness on average 15 years earlier than the latter.

Conclusion:

The current study confirmed a more severe progression of the retinal disease in USH1 patients rather than in USH2 patients. Furthermore, most visual symptoms (i.e., night blindness, visual acuity worsening) occurred at an earlier age in USH1 patients carrying mutations in MYO7A.
F usarium solani SUBRETINAL ABSCESS IN A PATIENT WITH ACUTE MYELOID LEUKEMIA
Authors: Schlaen Ariel , Ingolotti Mariana , Lorenzon Pablo , Mancini Jorge , Couto Cristobal , Casanova Maria , Kusminsky Gustavo , Tisi Baña Matias , Pineda Gloria , Rima Alejandra , Saravia Mario
Published: November 2016

Purpose:

To report on a case of Fusarium solani subretinal abscess in a patient with acute myeloid leukemia treated with an allogenic bone marrow transplant.

Methods:

A 47-year-old male with a history of acute myeloid leukemia with intermediate cytogenetic risk was admitted in our hospital. The disease relapsed after two cycles of chemotherapy. He was then treated with an allogenic bone marrow transplant, with busulfan, cyclophosphamide, and thymoglobulin. One week after the procedure, a sepsis of unknown origin in neutropenia occurred. Blood cultures and sputum were negative for bacteria and fungi. At the eighth week after the procedure, the patient had acute vision loss of the right eye. Funduscopy in the right eye revealed an inferior temporal yellowish white elevated lesion of approximately 10 disk areas and superficial perifoveal and perilesional hemorrhages.

Results:

Vitrectomy was performed and samples from the vitreous and the subretinal abscess material were sent for analysis. Vitreous and subretinal specimens grew colonies of a fungus morphologically consistent with F. solani.

Conclusion:

Fusarium solani should be included in the differential diagnosis of subretinal abscesses.
Mechanical Circulatory Support: Heart Failure Therapy “in Motion”
Authors: Ensminger Stephan M. , Gerosa Gino , Gummert Jan F. , Falk Volkmar
Published: November 2016

Because the first generation of pulsatile-flow devices was primarily used to bridge the sickest patients to transplantation (bridge-to-transplant therapy), the current generation of continuous-flow ventricular assist devices qualifies for destination therapy for patients with advanced heart failure who are ineligible for transplantation. The first-generation devices were associated with frequent adverse events, limited mechanical durability, and patient discomfort due device size. In contrast, second-generation continuous-flow devices are smaller, more quiet, and durable, thus resulting in less complications and significantly improved survival rates. Heart transplantation remains an option for a limited number of patients only, and this fact has also triggered the discussion about the optimal timing for device implantation. The increasing use of continuous-flow devices has resulted in new challenges, such as adverse events during long-term support, and high hospital readmission rates. In addition, there are a number of device-related complications including mechanical problems such as device thrombosis, percutaneous driveline damage, as well as conditions such as hemolysis, infection, and cerebrovascular accidents. This review provides an overview of the evolution of mechanical circulatory support systems from bridge to transplantation to destination therapy including technological advances and clinical improvements in long-term patient survival and quality of life. In addition, recent changes in device implant strategies and current trials are reviewed and discussed. A brief glimpse into the future of mechanical circulatory support therapy will summarize the innovations that may soon enter clinical practice.
Get the Message: A Teen Distracted Driving Program
Authors: Adeola Ruth , Omorogbe Ashleigh , Johnson Abree
Published: November 2016

Elimination of distracted driving is becoming a public health priority. Each day, an average of 8 people are killed due to a distracted driver in the United Sates. Although all drivers are at risk, research has indicated that teenage drivers are overrepresented in motor vehicle crashes due to distracted driving. Teenage drivers are hindered by limited driving experience, and the illusion of invincibility is a common phase in social and cognitive adolescent development. “Get the Message: A Teenage Distracted Driving Program” was established at the R Adams Cowley Shock Trauma Center to identify, define, and measure the factors that contribute to distracted driving in teens. A convenience sample of 1,238 teenagers in this study represented all 50 states in the United States, the District of Columbia, Puerto Rico, Canada, and 21 other countries. At the beginning of each program, a presurvey is administered to assess baseline behavior, attitude, and knowledge regarding distracted driving. After completing the program, teens complete a postsurvey to measure proposed changes in driving behaviors, attitude, and knowledge. The program employs the use of a slide presentation, hospital tour, video, and survivor's testimony to influence teen driving behaviors and increase knowledge. Research has indicated that an increase in the Health Belief Model constructs may enhance engagement in health-promoting behaviors, such as safe driving practices in teens. Based on the postsurvey results, the reduction in projected phone use while driving in this teen population indicates the effectiveness of this hospital-based teen distracted driving program.
Neonatal ICU System Safety
Authors: Zhang Xin , Lee Shih-Yu , Chen Jingli , Liu Huaping
Published: November 2016

This study analyzed risk factors for medication/near-miss errors in the neonatal intensive care unit by using Grey Relational Analysis based on self-incident reports from staff nurses. The ASSESS-ERR Medication System Worksheet was used. A total of 156 medication/near-miss errors were found across 5 stages of the medication use process. The order prescribing stage had the most errors. The highest systemic risk factors were critical drug information missing; environmental, staffing, and workflow problems; and lack of staff education.
Pediatric Ventilator-Associated Infections: The Ventilator-Associated INfection Study
Authors: Willson Douglas F. , Hoot Michelle , Khemani Robinder , Carrol Christopher , Kirby Aileen , Schwarz Adam , Gedeit Rainer , Nett Sholeen T. , Erickson Simon , Flori Heidi , Hays Spencer , Hall Mark
Published: November 2016

Objective:

Suspected ventilator-associated infection is the most common reason for antibiotics in the PICU. We sought to characterize the clinical variables associated with continuing antibiotics after initial evaluation for suspected ventilator-associated infection and to determine whether clinical variables or antibiotic treatment influenced outcomes.

Design:

Prospective, observational cohort study conducted in 47 PICUs in the United States, Canada, and Australia. Two hundred twenty-nine pediatric patients ventilated more than 48 hours undergoing respiratory secretion cultures were enrolled as “suspected ventilator-associated infection” in a prospective cohort study, those receiving antibiotics of less than or equal to 3 days were categorized as “evaluation only,” and greater than 3 days as “treated.” Demographics, diagnoses, comorbidities, culture results, and clinical data were compared between evaluation only and treated subjects and between subjects with positive versus negative cultures.

Setting:

PICUs in 47 hospitals in the United States, Canada, and Australia.

Subjects:

All patients undergoing respiratory secretion cultures during the 6 study periods.

Interventions:

None.

Measurements and Main Results:

Treated subjects differed from evaluation-only subjects only in frequency of positive cultures (79% vs 36%; p < 0.0001). Subjects with positive cultures were more likely to have chronic lung disease, tracheostomy, and shorter PICU stay, but there were no differences in ventilator days or mortality. Outcomes were similar in subjects with positive or negative cultures irrespective of antibiotic treatment. Immunocompromise and higher Pediatric Logistic Organ Dysfunction scores were the only variables associated with mortality in the overall population, but treated subjects with endotracheal tubes had significantly lower mortality.

Conclusions:

Positive respiratory cultures were the primary determinant of continued antibiotic treatment in children with suspected ventilator-associated infection. Positive cultures were not associated with worse outcomes irrespective of antibiotic treatment although the lower mortality in treated subjects with endotracheal tubes is notable. The necessity of continuing antibiotics for a positive respiratory culture in suspected ventilator-associated infection requires further study.
Sexual Behavior and Vaginal Practices During Pregnancy and Postpartum: Implications for HIV Prevention Strategies
Authors: Kinuthia John , Richardson Barbra A. , Drake Alison L. , Matemo Daniel , Unger Jennifer A. , McClelland Raymond S. , John-Stewart Grace
Published: November 2016

Background:

Understanding sexual behaviors and vaginal practices of pregnant and breastfeeding women in sub-Saharan Africa is critical to inform HIV prevention strategies during these periods.

Methods:

HIV-uninfected women presenting for antenatal care in western Kenya were enrolled and followed through 36 weeks postpartum. Sexual behavior and vaginal practices were ascertained by structured questionnaires. Logistic regression was used to assess correlates of unprotected sex, vaginal washing, and vaginal drying.

Results:

Among 1252 women enrolled, 78.4% were married (of whom 15.1% were in polygamous unions), 1.4% had a known HIV-infected partner, and 33.6% had a partner of unknown HIV status. At enrollment, 58.5% reported sex in the past month (94.3% unprotected) and 4.5% reported forced sex. Odds of unprotected sex at enrollment was >11-fold higher in married than in unmarried women (P < 0.001) and lower among women who reported partners of unknown HIV status or HIV-infected compared with HIV-uninfected partners. Median time to postpartum resumption of sex was 7 weeks (interquartile range 4–12). Prevalence of unprotected sex in the past week increased from 6.6% to 60.0% between 2 and 36 weeks postpartum (P < 0.001). Vaginal washing was reported by 60.1% of women at enrollment and prevalence remained stable postpartum; vaginal drying was reported by 17.9% at enrollment and decreased to 6.1% at 36 weeks postpartum (P < 0.001). Vaginal washing and drying were associated with forced sex.

Conclusions:

High rates of unknown partner HIV status, polygamy, and less frequent condom use among pregnant/postpartum women underscore the need for female-controlled HIV prevention interventions. Vaginal washing and drying may present challenges to microbicide use.
Brief Report: Soluble CD163 in CMV-Infected and CMV-Uninfected Subjects on Virologically Suppressive Antiretroviral Therapy in the ICONA Cohort
Authors: Vita Serena , Lichtner Miriam , Marchetti Giulia , Mascia Claudia , Merlini Esther , Cicconi Paola , Vullo Vincenzo , Viale Pierluigi , Costantini Andrea , D'Arminio Monforte Antonella ,   for ICONA Foundation Study Group
Published: November 2016

Aims:

To contribute to the understanding of the role played by cytomegalovirus (CMV) in sustaining monocyte/macrophage-mediated immune activation in antiretroviral therapy treated HIV-infected subjects.

Design and Methods:

We selected 23 CMV-uninfected and 46 CMV-infected HIV+ subjects, matched for age, CD4 nadir, HIV infection duration, and viral hepatitis serostatus. All subjects were on successful antiretroviral therapy since at least 1 year. A group of 16 healthy donors with similar age and sex was also included. Plasma levels of tumor necrosis factor–alpha, interleukin-6, sCD163, sCD14, and CMV immunoglobulin G levels were measured in duplicate with human enzyme-linked immunosorbent assay kits.

Results:

We found significantly higher sCD163 plasma levels in HIV+CMV+ compared with HIV+CMV− subjects and healthy donors. This augmentation was confirmed also when subjects positive for hepatitis C virus–Ab were excluded from analysis. Interestingly, a correlation between anti-CMV immunoglobulin G levels and sCD163, tumor necrosis factor–alpha, interleukin-6, and sCD14 in HIV+CMV+ subjects was found.

Conclusions:

CMV coinfection could be a major driver of monocyte/macrophage activation in virally suppressed HIV+ individuals and might explain the increased risk of non-AIDS morbidity/mortality in HIV/CMV-coinfected subjects.
Managing chronic kidney disease in the older adults living with HIV
Authors: Post Frank A.
Published: November 2016

Purpose of review

HIV replication and immunodeficiency are important risk factors for chronic kidney disease (CKD). Widespread use of antiretrovirals that may affect kidney function underscores the need for monitoring kidney function, allowing early detection of drug-induced kidney injury and identification of patients who may benefit from antiretroviral therapy switches.

Recent findings

Several cohorts have reported an increased incidence of CKD with tenofovir [tenofovir disoproxil fumarate (TDF)], atazanavir, and lopinavir, and CKD risk scores have been developed to identify those most at risk of kidney disease progression while receiving these agents. Recent data suggest that TDF discontinuation and substitution of atazanavir or lopinavir with darunavir may stabilize or improve renal function. Tenofovir alafenamide (TAF) is a new tenofovir formulation with minimal effect on renal tubular function. Patients with preserved or mild–moderately impaired renal function who switched from TDF to TAF-containing regimens experienced rapid and sustained improvement in proteinuria and stable renal function, suggesting that TAF will be the preferred tenofovir formulation for patients with CKD and those at increased risk of developing CKD.

Suppression of HIV replication and antiretroviral switches away from TDF and atazanavir are important measures to maintain kidney function and reduce CKD risk in older adults living with HIV.
Community-acquired bacterial meningitis
Authors: Costerus Joost M. , Brouwer Matthijs C. , Bijlsma Merijn W. , van de Beek Diederik
Published: November 2016

Purpose of review

Bacterial meningitis is a medical emergency and is associated with a high disease burden. We reviewed recent progress in the management of patients with community-acquired bacterial meningitis.

Recent findings

The worldwide burden of disease of bacterial meningitis remains high, despite the decreasing incidence following introduction of routine vaccination campaigns. Delay in diagnosis and treatment remain major concerns in the management of acute bacterial meningitis. European Society of Clinical Microbiology and Infectious Diseases guidelines strive for a door-to-antibiotic-time less than 1 h. Polymerase chain reaction (PCR) has emerged as an important diagnostic tool to identify the causative organism. Point-of-care tests using fast multiplex PCR have been developed, but additional value has not been proven. Although anecdotal observations advocate pressure-based management, a randomized controlled trial will need to be performed first to determine efficacy and safety of such an aggressive treatment approach. Adjunctive dexamethasone remains the only adjunctive therapy with proven efficacy.

The incidence of bacterial meningitis has been decreasing after the implementation of effective vaccines. Treatment should be administered as soon as possible and time to treatment should not exceed 1 h.
Speed in Clinical Magnetic Resonance
Authors: Runge Val M. , Richter Johannes K. , Heverhagen Johannes T.
Published: November 2016

The relevant clinical accelerated magnetic resonance techniques that are available currently for routine patient examinations are reviewed, presenting and discussing the benefits therein when compared with more conventional scans. The focus is on clinical use and practicality, with the review divided into 3 sections. Improvements in 3-dimensional acquisition are first discussed, specifically controlled aliasing in parallel imaging results in higher acceleration, related radial techniques, and CAIPI-Dixon-TWIST-VIBE. Simultaneous multislice imaging is then reviewed, focusing on current implementation for 2-dimensional imaging, including both echo-planar and fast spin echo techniques. The final topic is that of sparse reconstruction (data sparsity), discussing the principles therein, challenges, and current applications. Guidance in terms of clinical use for accelerated techniques is provided, focusing on enabling faster and improved clinical scan results.
Alcohol Use Disorder as a Possible Predictor of Electroconvulsive Therapy Response
Authors: Aksay Suna Su , Hambsch Melanie , Janke Christoph , Bumb Jan Malte , Kranaster Laura , Sartorius Alexander
Published: November 2016

Introduction

Two rapidly acting antidepressive treatment forms, namely, electroconvulsive therapy (ECT) and ketamine, possibly share a common mechanism of action primarily involving alterations of neurotransmission (glutamate and γ-aminobutyric acid levels). Because patients receiving ketamine and with a coexistent family history of an alcohol use disorder (AUD) seem to benefit from consistent and longer lasting antidepressive effects, we hypothesized better treatment response in ECT patients with an own history or a family history of an AUD.

Method

One hundred forty-one psychiatric inpatients with a major depressive episode, who were treated with ECT, were enrolled into this retrospective study. Age, sex, family or personal history of alcohol or benzodiazepine use disorder, ECT response data, and ECT treatment-related data were collected and analyzed with ordinal logistic regression and Fisher exact tests.

Results

Twenty-one percent of all patients had their own history of an AUD, 11% had their own history of a benzodiazepine use disorder, and 11% reported on a positive family history of alcohol or benzodiazepine use disorder. The logistic regression analyses revealed that only patient's own history of an AUD predicts a better ECT response (P = 0.031; odds ratio, 2.1; Fisher exact test, P = 0.006).

Conclusions

Within the limitations of a retrospective study, a history of an AUD seems to be a positive predictor for an ECT response in patients experiencing a major depressive episode, which has not been found in 2 earlier studies. Findings are in line with neurobiological hypotheses of excitatory/inhibitory neurotransmitter changes with ketamine and ECT.
Probabilistic divergence time estimation without branch lengths: dating the origins of dinosaurs, avian flight and crown birds
Authors: Lloyd G. T. , Bapst D. W. , Friedman M. , Davis K. E.
Published: November 2016

Branch lengths—measured in character changes—are an essential requirement of clock-based divergence estimation, regardless of whether the fossil calibrations used represent nodes or tips. However, a separate set of divergence time approaches are typically used to date palaeontological trees, which may lack such branch lengths. Among these methods, sophisticated probabilistic approaches have recently emerged, in contrast with simpler algorithms relying on minimum node ages. Here, using a novel phylogenetic hypothesis for Mesozoic dinosaurs, we apply two such approaches to estimate divergence times for: (i) Dinosauria, (ii) Avialae (the earliest birds) and (iii) Neornithes (crown birds). We find: (i) the plausibility of a Permian origin for dinosaurs to be dependent on whether
Nyasasaurus
is the oldest dinosaur, (ii) a Middle to Late Jurassic origin of avian flight regardless of whether
Archaeopteryx
or
Aurornis
is considered the first bird and (iii) a Late Cretaceous origin for Neornithes that is broadly congruent with other node- and tip-dating estimates. Demonstrating the feasibility of probabilistic time-scaling further opens up divergence estimation to the rich histories of extinct biodiversity in the fossil record, even in the absence of detailed character data.
How the embryonic chick brain twists
Authors: Chen Zi , Guo Qiaohang , Dai Eric , Forsch Nickolas , Taber Larry A.
Published: November 2016

During early development, the tubular embryonic chick brain undergoes a combination of progressive ventral bending and rightward torsion, one of the earliest organ-level left–right asymmetry events in development. Existing evidence suggests that bending is caused by differential growth, but the mechanism for the predominantly rightward torsion of the embryonic brain tube remains poorly understood. Here, we show through a combination ofin vitroexperiments, a physical model of the embryonic morphology and mechanics analysis that the vitelline membrane (VM) exerts an external load on the brain that drives torsion. Our theoretical analysis showed that the force is of the order of 10 micronewtons. We also designed an experiment to use fluid surface tension to replace the mechanical role of the VM, and the estimated magnitude of the force owing to surface tension was shown to be consistent with the above theoretical analysis. We further discovered that the asymmetry of the looping heart determines the chirality of the twisted brain via physical mechanisms, demonstrating the mechanical transfer of left–right asymmetry between organs. Our experiments also implied that brain flexure is a necessary condition for torsion. Our work clarifies the mechanical origin of torsion and the development of left–right asymmetry in the early embryonic brain.
Constraint-based stoichiometric modelling from single organisms to microbial communities
Authors: Gottstein Willi , Olivier Brett G. , Bruggeman Frank J. , Teusink Bas
Published: November 2016

Microbial communities are ubiquitously found in Nature and have direct implications for the environment, human health and biotechnology. The species composition and overall function of microbial communities are largely shaped by metabolic interactions such as competition for resources and cross-feeding. Although considerable scientific progress has been made towards mapping and modelling species-level metabolism, elucidating the metabolic exchanges between microorganisms and steering the community dynamics remain an enormous scientific challenge. In view of the complexity, computational models of microbial communities are essential to obtain systems-level understanding of ecosystem functioning. This review discusses the applications and limitations of constraint-based stoichiometric modelling tools, and in particular flux balance analysis (FBA). We explain this approach from first principles and identify the challenges one faces when extending it to communities, and discuss the approaches used in the field in view of these challenges. We distinguish between steady-state and dynamic FBA approaches extended to communities. We conclude that much progress has been made, but many of the challenges are still open.
Structural colour from helicoidal cell-wall architecture in fruits ofMargaritaria nobilis
Authors: Vignolini Silvia , Gregory Thomas , Kolle Mathias , Lethbridge Alfie , Moyroud Edwige , Steiner Ullrich , Glover Beverley J. , Vukusic Peter , Rudall Paula J.
Published: November 2016

The bright and intense blue-green coloration of the fruits ofMargaritaria nobilis(Phyllanthaceae) was investigated using polarization-resolved spectroscopy and transmission electron microscopy. Optical measurements of freshly collected fruits revealed a strong circularly polarized reflection of the fruit that originates from a cellulose helicoidal cell wall structure in the pericarp cells. Hyperspectral microscopy was used to capture the iridescent effect at the single-cell level.
A potential mechanism for the first-person inner sensation of memory provides evidence for a relationship between learning and LTP induction
Authors: Vadakkan Kunjumon I.
Published: November 2016

Large number of correlations have been observed between behavioral markers of memory and long-term potentiation (LTP). However, there are different non-correlated findings that need explanations. Examples include a) a delay of at least thirty seconds for LTP induction after stimulation that does not match with milliseconds of time required for associative learning, and b) the deficiency of the LTP mechanism for providing a structure-function mechanism for working memory. By viewing memories as first-person inner sensations, a derived mechanism can explain various features of LTP and its mismatched findings with that of normal learning.
Resting state functional coupling between the ascending synchronising system, limbic system and the default mode network via theta oscillations
Authors: Raniga Parnesh , Paton Bryan , Egan Gary F.
Published: November 2016

In order to better understand dysfunction in dementia and psychiatric illnesses, the underlying neuronal systems that give rise to normal memory and cognitive processes need to be better understood. Based on electrophysiological recordings in animals, theta oscillations have been proposed as an intrinsic mechanism for the orchestration of memory functions, especially episodic and autobiographical memory. Theta oscillations are controlled by the ascending synchronising system, a set of nucleui in the pontine tegmentum and basal forebrain. At a network level, the default mode network has been shown to be responsible for episodic and autobiographical.

Using resting state fMRI data, we show using an ICA approach, seed based connectivity and dynamic causal modelling that the ascending synchronising system is coupled to the medial temporal lobe nodes including the hippocampus and parahippocampal gyrus and with the default mode network. Our results provide thus support the role of theta oscillations in memory function and coordination at a network level.

Highlights

Resting state functional coupling between the DMN, MTL and ascending synchronising system.

Theta oscillations may be the basis of this coupling given the role of these structures in control of theta.

Theta oscillations have been implicated in memory, cognition and predictive coding.

DMN, MTL and ASS are implicated in Alzheimer’s disease.

Abbreviations

MRI

Magnetic resonance imaging

fMRI

functional magnetic resonance imaging

rs-fmri

resting state functional magnetic resonance imaging

PnO

Pontine nucleus oralis

SuM

Supra-mamillary nucleus.

MS

Medial septum

DB

Diagonal band of Broca.

VTA

ventral tegmental area

PCC

Posterior cingulate cortex

HC

Hippocampus

ARAS

Ascending reticular activating system

ASS

Ascending synchronising system

DMN

Default Mode Network

aMPFC

Anterior Medial Prefrontal Cortex

pIPL

Posterior inferior parietal lobule

NBM

Nucleus Basalis Mynert

DCM

Dynamic causal modelling

PHG

Parahippocampal Gyrus
Ribo-attenuators: novel elements for reliable and modular riboswitch engineering
Authors: Folliard Thomas , Mertins Barbara , Prescott Thomas P , Steel Harrison , Newport Thomas , Jones Christopher W , Bayer Travis , Armitage Judith P , Papachristodoulou Antonis , Rothschild Lynn J
Published: November 2016

Riboswitches are structural genetic regulatory elements that directly couple the sensing of small molecules to gene expression. They have considerable potential for applications throughout synthetic biology and bio-manufacturing as they are able to sense a wide range of small molecules and regulate gene expression in response. Despite over a decade of research they have yet to reach this considerable potential as they cannot yet be treated as modular components. This is due to several limitations including sensitivity to changes in genetic context, low tunability, and variability in performance. To overcome the associated difficulties with riboswitches, we have designed and introduced a novel genetic element called a Ribo-attenuator in Bacteria. This genetic element allows for predictable tuning, insulation from contextual changes, and a reduction in expression variation. Ribo-attenuators allow riboswitches to be treated as truly modular and tunable components, and thus increases their reliability for a wide range of applications.
Anchored Phylogenomics of Angiosperms I: Assessing the Robustness of Phylogenetic Estimates
Authors: Buddenhagen Chris , Lemmon Alan R. , Lemmon Emily Moriartya , Bruhl Jeremy , Cappa Jennifer , Clement Wendy L. , Donoghue Michael J. , Edwards Erika J. , Hipp Andrew L. , Kortyna Michelle , Mitchell Nora , Moore Abigail , Prychid Christina J. , Segovia-Salcedo Maria C. , Simmons Mark P. , Soltis Pamela S. , Wanke Stefan , Mast Austin
Published: November 2016

An important goal of the angiosperm systematics community has been to develop a shared approach to molecular data collection, such that phylogenomic data sets from different focal clades can be combined for meta-studies across the entire group. Although significant progress has been made through efforts such as DNA barcoding, transcriptome sequencing, and whole-plastid sequencing, the community current lacks a cost efficient methodology for collecting nuclear phylogenomic data across all angiosperms. Here, we leverage genomic resources from 43 angiosperm species to develop enrichment probes useful for collecting ~500 loci from non-model taxa across the diversity of angiosperms. By taking an anchored phylogenomics approach, in which probes are designed to represent sequence diversity across the group, we are able to efficiently target loci with sufficient phylogenetic signal to resolve deep, intermediate, and shallow angiosperm relationships. After demonstrating the utility of this resource, we present a method that generates a heat map for each node on a phylogeny that reveals the sensitivity of support for the node across analysis conditions, as well as different locus, site, and taxon schemes. Focusing on the effect of locus and site sampling, we use this approach to statistically evaluate relative support for the alternative relationships among eudicots, monocots, and magnoliids. Although the results from supermatrix and coalescent analyses are largely consistent across the tree, we find support for this deep relationship to be more sensitive to the particular choice of sites and loci when a supermatrix approach as employed. Averaged across analysis approaches and data subsampling schemes, our data support a eudicot-monocot sister relationship, which is supported by a number of recent angiosperm studies.
Rotamer libraries for the high-resolution design of β-amino acid foldamers
Authors: Watkins Andrew M. , Craven Timothy W. , Renfrew P. Douglas , Arora Paramjit S. , Bonneau Richard
Published: November 2016

β-amino acids offer attractive opportunities to develop biologically active peptidomimetics, either employed alone or in conjunction with natural α-amino acids. Owing to their potential for unique conformational preferences that deviate considerably from α-peptide geometries, β-amino acids greatly expand the possible chemistries and physical properties available to polyamide foldamers. Completein silicosupport for designing new molecules incorporating nonnatural amino acids typically requires representing their side chain conformations as sets of discrete rotamers for model refinement and sequence optimization. Such rotamer libraries are key components of several state of the art design frameworks. Here we report the development, incorporation in to the Rosetta macromolecular modeling suite, and validation of rotamer libraries for β3-amino acids.
Asymmetrical representation of the upper and lower visual fields in oculomotor maps
Authors: Wang Zhiguo , Wang Benchi , Finkbeiner Matthew
Published: November 2016

The striate area devoted to the lower visual field (LVF) is larger than that devoted to the upper visual field (UVF). A similar anatomical asymmetry also exists in the LGN. Here we take advantage of two experimental tasks that are known to modulate the direction and amplitude of saccades to demonstrate a visual field asymmetry in oculomotor maps. Participants made visually guided saccades. In Experiment 1, the saccade target was accompanied by a visual distractor. The distractor’s presence modulated the direction of saccades, and this effect was much stronger for LVF targets. In Experiment 2, the temporal gap between the offset of the fixation stimulus and the onset of the saccade target was manipulated. This manipulation modulated the amplitude of saccades and this modulation was stronger for saccades towards UVF targets. Taken together, these results suggest that the representation of both meridians and eccentricities in the LVF is compressed in oculomotor maps.
A Deep Boosting Based Approach for Capturing the Sequence Binding Preferences of RNA-Binding Proteins from High-Throughput CLIP-Seq Data
Authors: Li Shuya , Dong Fanghong , Wu Yuexin , Zhang Sai , Zhang Chen , Liu Xiao , Jiang Tao , Zeng Jianyang
Published: November 2016

Characterizing the binding behaviors of RNA-binding proteins (RBPs) is important for understanding their functional roles in gene expression regulation. However, current high-throughput experimental methods for identifying RBP targets, such as CLIP-seq and RNAcompete, usually suffer from the false positive and false negative issues. Here, we develop a deep boosting based machine learning approach, called DeBooster, to accurately model the binding sequence preferences and identify the corresponding binding targets of RBPs from CLIP-seq data. Comprehensive validation tests have shown that DeBooster can outperform other state-of-the-art approaches in predicting RBP targets and recover false negatives that are common in current CLIP-seq data. In addition, we have demonstrated several new potential applications of DeBooster in understanding the regulatory functions of RBPs, including the binding effects of the RNA helicase MOV10 on mRNA degradation, the influence of different binding behaviors of the ADAR proteins on RNA editing, as well as the antagonizing effect of RBP binding on miRNA repression. Moreover, DeBooster may provide an effective index to investigate the effect of pathogenic mutations in RBP binding sites, especially those related to splicing events. We expect that DeBooster will be widely applied to analyze large-scale CLIP-seq experimental data and can provide a practically useful tool for novel biological discoveries in understanding the regulatory mechanisms of RBPs.
Selection on the FADS region in Europeans
Authors: Buckley Matthew T. , Racimo Fernando , Allentoft Morten E. , Jensen Majken K. , Jonsson Anna , Huang Hongyan , Hormozdiari Farhad , Sikora Martin , Marnetto Davide , Eskin Eleazar , Jørgensen Marit E. , Grarup Niels , Pedersen Oluf , Hansen Torben , Kraft Peter , Willerslev Eske , Nielsen Rasmus
Published: November 2016

FADSgenes encode fatty acid desaturases that are important for the conversion of short chain polyunsaturated fatty acids (PUFAs) to long chain fatty acids. Prior studies indicate that theFADSgenes have been subjected to strong positive selection in Africa, South Asia, Greenland, and Europe. By comparingFADSsequencing data from present-day and Bronze Age (5-3k years ago) Europeans, we identify possible targets of selection in the European population, which suggest that selection has targeted different alleles in theFADSgenes in Europe than it has in South Asia or Greenland. The alleles showing the strongest changes in allele frequency since the Bronze Age show associations with expression changes and multiple lipid-related phenotypes. Furthermore, the selected alleles are associated with a decrease in linoleic acid and an increase in arachidonic and eicosapentaenoic acids among Europeans; this is an opposite effect of that observed for selected alleles in Inuit from Greenland. We show that multiple SNPs in the region affect expression levels and PUFA synthesis. Additionally, we find evidence for a gene-environment interaction influencing low-density lipoprotein (LDL) levels between alleles affecting PUFA synthesis and PUFA dietary intake: carriers of the selected, derived allele have diminished increases in LDL cholesterol with a higher intake of PUFAs. We hypothesize that the selective patterns observed in Europeans were driven by a change in dietary composition of fatty acids following the transition to agriculture, resulting in a lower intake of arachidonic acid and eicosapentaenoic acid, but a higher intake of linoleic acid and α-linolenic acid.
Phage mobility is a core determinant of phage-bacteria coexistence in biofilms
Authors: Simmons Matthew , Drescher Knut , Nadell Carey D. , Bucci Vanni
Published: November 2016

Many bacteria are adapted for attaching to surfaces and for building complex communities, termed biofilms. The biofilm mode of life is predominant in bacterial ecology. So, too, is exposure of bacteria to ubiquitous viral pathogens, termed bacteriophages. Although biofilmphage encounters are likely to be very common in nature, little is known about how phages might interact with biofilm-dwelling bacteria. It is also unclear how the ecological dynamics of phages and their hosts depend on the biological and physical properties of the biofilm environment. To make headway in this area, here we develop the first biofilm simulation framework that captures key mechanistic features of biofilm growth and phage infection. Using these simulations, we find that the equilibrium state of interaction between biofilms and phages is governed largely by nutrient availability to biofilms, infection likelihood per host encounter, and the ability of phages to diffuse through biofilm populations. Interactions between the biofilm matrix and phage particles are thus likely to be of fundamental importance, controlling the extent to which bacteria and phages can coexist in natural contexts. Our results open avenues to new questions of host-parasite coevolution and horizontal gene transfer in spatially structured biofilm contexts.
Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution
Authors: Jonsson Vanessa D. , Blakely Collin M. , Lin Luping , Asthana Saurabh , Olivas Victor , Gubens Matthew A. , Matni Nikolai , Bastian Boris C. , Taylor Barry S. , Doyle John C. , Bivona Trever G.
Published: November 2016

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The success of targeted cancer therapy is limited by drug resistance that can result from tumor genetic heterogeneity. The current approach to address resistance typically involves initiating a new treatment after clinical/radiographic disease progression, ultimately resulting in futility in most patients. Towards a potential alternative solution, we developed a novel computational framework that uses human cancer profiling data to systematically identify dynamic, pre-emptive, and sometimes non-intuitive treatment strategies that can better control tumors in real-time. By studying lung adenocarcinoma clinical specimens and preclinical models, our computational analyses revealed that the best anti-cancer strategies addressed existing resistant subpopulations as they emerged dynamically during treatment. In some cases, the best computed treatment strategy used unconventional therapy switching while the bulk tumor was responding, a prediction we confirmed in vitro. The new framework presented here could guide the principled implementation of dynamic molecular monitoring and treatment strategies to improve cancer control.