bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of a Risk Stratification and Management Pathway for Acute Chest Pain in the Emergency Department
Authors: Baugh Christopher W. , Greenberg Jeffrey O. , Mahler Simon A. , Kosowsky Joshua M. , Schuur Jeremiah D. , Parmar Siddharth , Ciociolo George R. , Carr Christina W. , Ghazinouri Roya , Scirica Benjamin M.
Published: November 2016

Objectives:

Chest pain is a common complaint in the emergency department, and a small but important minority represents an acute coronary syndrome (ACS). Variation in diagnostic workup, risk stratification, and management may result in underuse, misuse, and/or overuse of resources.

Methods:

From July to October 2014, we conducted a prospective cohort study in an academic medical center by implementing a Standardized Clinical Assessment and Management Plan (SCAMP) for chest pain based on the HEART score. In addition to capturing adherence to the SCAMP algorithm and reasons for any deviations, we measured troponin sample timing; rates of stress test utilization; length of stay (LOS); and 30-day rates of revascularization, ACS, and death.

Results:

We identified 239 patients during the enrollment period who were eligible to enter the SCAMP, of whom 97 patients were entered into the pathway. Patients were risk stratified into one of 3 risk tiers: high (n = 3), intermediate (n = 40), and low (n = 54). Among low-risk patients, recommendations for troponin testing were not followed in 56%, and 11% received stress tests contrary to the SCAMP recommendation. None of the low-risk patients had elevated troponin measurements, and none had an abnormal stress test. Mean LOS in low-risk patients managed with discordant plans was 22:26 h/min, compared with 9:13 h/min in concordant patients (P < 0.001). Mean LOS in intermediate-risk patients with stress testing was 25:53 h/min, compared with 7:55 h/min for those without (P < 0.001). At 30 days, 10% of intermediate-risk patients and 0% of low-risk patients experienced an ACS event (risk difference 10% [0.7%–19%]); none experienced revascularization or death. The most frequently cited reason for deviation from the SCAMP was lack of confidence in the tool.

Conclusions:

Compliance with SCAMP recommendations for low- and intermediate-risk patients was poor, largely due to lack of confidence in the tool. However, in our study population, outcomes suggest that deviation from the SCAMP yielded no additional clinical benefit while significantly prolonging emergency department LOS.
The 6th Annual Acute Care Lecture Award: Survival Is Not Enough
Authors: Wruble Hakim Ellen
Published: November 2016

The healthcare climate has changed considerably over the last several years and transformation has been forced upon the profession, regardless of our readiness to accept its consequences. An inward look into the state of acute care education and practice is in order to determine if we are appropriately positioned to bring forth and to demonstrate our value to all constituents. While our successes should be celebrated, our gaps must be identified and addressed. Pivotal decisions must occur so that our identity can be clearly articulated, priorities appropriately established, and worth be undeniably evidenced. Lest not, we risk exclusion from populations and settings that could significantly benefit from functional reconciliation by movement experts knowledgeable in the management of acute illness complicated by chronic disease.
Carbon dioxide insufflation during colonoscopy in inflammatory bowel disease patients: a double-blind, randomized, single-center trial
Authors: Falt Přemysl , Šmajstrla Vít , Fojtík Petr , Hill Martin , Urban Ondřej
Published: November 2016

Objective

Bowel distension by insufflated air causes abdominal discomfort after colonoscopy. Carbon dioxide (CO2) instead of air insufflation during colonoscopy can reduce postprocedural discomfort in diagnostic and screening cases. Discomfort after colonoscopy and CO2 insufflation have never been studied in inflammatory bowel disease (IBD) patients, characterized by younger age, structural changes of the colon, and need for repeated and frequently uncomfortable colonoscopies. Our trial was designed to evaluate postprocedural discomfort associated with CO2 compared with air insufflation in unsedated or minimally sedated patients with known IBD.

Methods

In a double-blind, randomized, single-center study, 64 patients were randomized to either CO2 insufflation (CO2) or air insufflation colonoscopy (Air). Abdominal pain, bloating, and flatulence scores during 24 h after colonoscopy were recorded using a continuous scale of 0–10 (0=none, 10=maximum discomfort). The primary endpoint used for power calculation was bloating score at 1 h after colonoscopy.

Results

Pain, bloating, and flatulence scores at end, 1, and 3 h after colonoscopy were significantly lower in CO2 than in Air arm (P<0.001). Scores at 6, 12, and 24 h were comparable. Procedural parameters such as cecal and terminal ileum intubation rate, intubation and total time, pain during insertion, need for repositioning, and abdominal compression were not different between arms. No complications were recorded in the study.

Conclusion

Compared with air, CO2 insufflation significantly reduces abdominal pain, bloating, and flatulence scores during at least 3 h after colonoscopy in IBD patients, achieving comparable intraprocedural outcomes.
Oxygen Administration Does Not Influence the Prognosis of Acute Myocardial Infarction: A Meta-Analysis
Authors: Khan Abdur Rahman , Abdulhak Aref Bin , Luni Faraz Khan , Farid Talha A. , Riaz Haris , Ruzieh Mohammed , Pham Long , Hirsch Glenn , Bolli Roberto
Published: November 2016

Background:

The safety and efficacy of supplemental oxygen in acute myocardial infarction (AMI) remains unclear.

Study Question:

To evaluate the safety and efficacy of supplemental oxygen in patients who present with AMI.

Data Sources:

We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, ISI Web of Science, Scopus, and conference proceedings from inception through January 2016.

Study Design:

Eligible studies were randomized trials that evaluated the role of oxygen compared with room air in AMI. The clinical outcome measured was 30-day mortality, and odds ratio (OR) was calculated for the measured outcome. The Mantel–Haenszel method was used to pool 30-day mortality in a random-effects model. Sensitivity analysis was carried out to evaluate the effect of revascularization of the culprit artery on the outcome.

Results:

The pooled analysis suggested no difference in 30-day mortality [OR 1.09; 95% confidence interval (CI), 0.30–4.00; P = 0.89] between oxygen and room air. Metaregression demonstrated that all the between-study variance was because of coronary revascularization (P = 0.01, R2 = 1.0). A subgroup analysis suggested a trend toward increased mortality with oxygen (OR 3.26; 95% CI, 0.94–11.29; P = 0.06) when less than half of the patient population underwent revascularization. On the other hand, there was a nonsignificant numerical decrease in mortality with oxygen (OR 0.41; 95% CI, 0.14–1.19; P = 0.10) in the presence of coronary revascularization. Metaregression confirmed that all the between-study variance was because of coronary revascularization (P = 0.01, R2 = 1.0).

Conclusions:

In this meta-analysis, we found that the evidence on the safety and efficacy of oxygen was not only weak and inconsistent but also had modest statistical power. The variation in results was mainly because of the presence or absence of revascularization of the culprit artery. Adequately powered studies are needed to further delineate the role of oxygen in patients undergoing coronary revascularization.
Clinical Presentation of Acute Gastroenteritis in Children With Functional Abdominal Pain Disorders
Authors: Saps Miguel , Mintjens Stijn , Pusatcioglu Cenk K. , Cohen Daniel M. , Sternberg Petra
Published: November 2016

Visceral hypersensitivity and abnormal coping are common in children with functional abdominal pain disorders (FAPDs). Thus, it would be expected that children with visceral hypersensitivity would report more pain if their gut is acutely inflamed. The aim of the study was to compare clinical symptoms and somatization of children with and without FAPDs at time of an episode of acute gastroenteritis. Seventy children with acute gastroenteritis and their parents completed the Rome III Diagnostic Questionnaire for Pediatric Functional GI Disorders and the Children's Somatization Inventory. Twenty‐one percent of children were diagnosed with an FAPD. Children with FAPDs showed significantly more nongastrointestinal somatic symptoms than children without FAPDs. There were no significant differences in abdominal pain, nausea, vomiting, or school absenteeism between both groups at time of consultation.
Comparison of Cysts in Red and Green Images for Diabetic Macular Edema
Authors: Alhamami Mastour A. , Elsner Ann E. , Malinovsky Victor E. , Clark Christopher A. , Haggerty Bryan P. , Ozawa Glen Y. , Cuadros Jorge A. , Baskaran Karthikeyan , Gast Thomas J. , Litvin Taras V. , Muller Matthew S. , Brahm Shane G. , Young Stuart B. , Miura Masahiro
Published: November 2016

Purpose

To investigate whether cysts in diabetic macular edema are better visualized in the red channel of color fundus camera images, as compared with the green channel, because color fundus camera screening methods that emphasize short-wavelength light may miss cysts in patients with dark fundi or changes to outer blood retinal barrier.

Methods

Fundus images for diabetic retinopathy photoscreening were acquired for a study with Aeon Imaging, EyePACS, University of California Berkeley, and Indiana University. There were 2047 underserved, adult diabetic patients, of whom over 90% self-identified as a racial/ethnic identify other than non-Hispanic white. Color fundus images at nominally 45 degrees were acquired with a Canon Cr-DGi non-mydriatic camera (Tokyo, Japan) then graded by an EyePACS certified grader. From the 148 patients graded to have clinically significant macular edema by the presence of hard exudates in the central 1500 μm of the fovea, we evaluated macular cysts in 13 patients with cystoid macular edema. Age ranged from 33 to 68 years. Color fundus images were split into red, green, and blue channels with custom Matlab software (Mathworks, Natick, MA). The diameter of a cyst or confluent cysts was quantified in the red-channel and green-channel images separately.

Results

Cyst identification gave complete agreement between red-channel images and the standard full-color images. This was not the case for green-channel images, which did not expose cysts visible with standard full-color images in five cases, who had dark fundi. Cysts appeared more numerous and covered a larger area in the red channel (733 ± 604 μm) than in the green channel (349 ± 433 μm, P < .006).

Conclusions

Cysts may be underdetected with the present fundus camera methods, particularly when short-wavelength light is emphasized or in patients with dark fundi. Longer wavelength techniques may improve the detection of cysts and provide more information concerning the early stages of diabetic macular edema or the outer blood retinal barrier.
Pilot Mechanistic Study of Insulin Modulation of Somatotrophic Hormones, Inflammation, and Lipid Metabolism During Critical Illness in Children*
Authors: Branco Ricardo G. , Garcia Pedro Celiny R. , Piva Jefferson P. , Conrado Geniara S. , Cabral Felipe , Korb Cecilia , Fiori Humberto , Baldisserotto Matteo , Tasker Robert C.
Published: November 2016

Objectives:

To evaluate the mechanism of insulin modulation on somatotrophic response, inflammation, and lipid metabolism in critically ill children.

Design:

Open-label randomized mechanistic study.

Setting:

Two-center, tertiary PICU study.

Patients:

Thirty critically ill children between 1 month and 14 years old, requiring mechanical ventilation and with evidence of two or more organ system failures.

Interventions:

Randomized physiologic design of hyperinsulinemic-euglycemic clamp using continuous insulin infusion at 0.1 U/kg/hr versus conventional management.

Measurements and Main Results:

Thirteen children underwent hyperinsulinemic-euglycemic clamp. Blood samples for somatotrophic, inflammatory, and metabolic evaluation were obtained before randomization, and 24 and 72 hours later. A growth hormone oscillation profile was obtained during the first night. There was no difference between groups at baseline. Growth hormone resistance, increased proinflammatory cytokines, and increased lipolysis with low lipoprotein levels were present in all patients. Hyperinsulinemic-euglycemic clamp did not affect growth hormone, insulin-like growth factor-1 or insulin-like growth factor binding protein-3 levels. By day 2, insulin reduced insulin-like growth factor binding protein-1 levels. Tumor necrosis factor-α and interleukin-1β were similar in both groups, whereas interleukin-6 levels reduced over time only in children receiving hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamp also decreased free fatty acid levels, which was accompanied by increased low-density lipoprotein cholesterol and relative increase in high-density lipoprotein levels. Total cholesterol and triglycerides were unchanged.

Conclusions:

Insulin does not reverse most of the somatotrophic changes induced by the stress of critical illness. Rather, it may improve lipid metabolism and down-regulate some markers of the inflammatory response.
Glomangiomyoma of the Vagina: A Report of 2 Cases and Literature Review
Authors: Rahimi Siavash , Marani Carla , Balega Janos , Hirschowitz Lynn
Published: November 2016

We report 2 cases of vaginal glomangiomyoma in a 53-year-old who presented with a painful vaginal mass, and a 56-year-old who had postmenopausal bleeding and in whom an incidental vaginal mass was identified and resected at the time of hysterectomy. Histologic examination of the resected masses showed solid, circumscribed, benign, smooth muscle–predominant tumors with interspersed small islands of epithelioid glomus cells. The glomus cells were intimately related to small-caliber blood vessels and showed no cytologic atypia or mitotic activity. The tumor cells showed diffuse expression of smooth muscle actin, CD34, and focal expression of h-caldesmon, vimentin, and estrogen receptor. No immunolabeling for calponin B or desmin was found. To our knowledge, there are only isolated reports of vaginal glomus tumors, and these are the first reported case of vaginal glomangiomyoma in the literature.
Virological Blips and Predictors of Post Treatment Viral Control After Stopping ART Started in Primary HIV Infection
Authors: Fidler Sarah , Olson Ashley D. , Bucher Heiner C. , Fox Julie , Thornhill John , Morrison Charles , Muga Roberto , Phillips Andrew , Frater John , Porter Kholoud ,   on behalf of CASCADE Collaboration in EuroCoord
Published: November 2016

Background:

Few individuals commencing antiretroviral therapy (ART) in primary HIV infection (PHI) maintain undetectable viremia after treatment cessation. Associated factors remain unclear given the importance of the phenomenon to cure research.

Methods:

Using CASCADE data of seroconverters starting ART in PHI (≤6 months from seroconversion), we estimated proportions experiencing viral blips (>400 copies followed by <400 copies HIV-RNA/mL without alteration of regimen) while on ART. We used Cox models to examine the association between time from ART stop to loss of control (2 consecutive measurements >1000 copies per milliliter) and magnitude and frequency of blips while on ART, time from seroconversion to ART, time on ART, adjusting for mean number of HIV-RNA measurements/year while on ART, and other confounders.

Results:

Seven hundred seventy-eight seroconverters started ART in PHI with ≥3 HIV-RNA measurements. Median interquartile range (IQR) ART duration was 16.2 (8.0–35.9) months, within which we observed 13% with ≥1 blip. Of 228 who stopped ART, 119 rebounded; time to loss of control was associated with longer interval between seroconversion and ART initiation [hazard ratio (HR) = 1.16 per month; 1.04, 1.28], and blips while on ART (HR = 1.71 per blip; 95% confidence interval = 0.94 to 3.10). Longer time on ART (HR = 0.84 per additional month; 0.76, 0.92) was associated with lower risk of losing control. Of 228 stopping ART, 22 (10%) maintained post treatment control (PTC), ie, HIV-RNA <50 copies per milliliter ≥24 months after ART cessation.

Conclusion:

HIV viral blips on therapy are associated with subsequent viral rebound on stopping ART among individuals treated in PHI. Longer duration on ART is associated with a greater chance of PTC.
Clinical Significance of Late Phase of Lung Perfusion Blood Volume (Lung Perfusion Blood Volume) Quantified by Dual-Energy Computed Tomography in Patients With Pulmonary Thromboembolism
Authors: Koike Hirofumi , Sueyoshi Eijun , Sakamoto Ichiro , Uetani Masataka
Published: November 2016

Purpose:

Using dual-energy computed tomography (DECT), we quantified the lung perfusion blood volume (PBV) in the late phase, which may reflect both the pulmonary artery and systemic collateral flow. We then investigated the clinical significance of late-phase lung PBV values.

Materials and Methods:

We retrospectively studied 206 patients (266 scans) who underwent early-phase and late-phase DECT. The patients were divided into 2 groups depending on whether or not they had pulmonary thromboembolism (PTE) (n=94 and 112). Patients with PTE were further divided into 2 subgroups, depending on whether they had acute PTE or chronic PTE (n=66 and 28). Pulmonary artery enhancement (PAenh) was measured on DECT. We then calculated the [lung PBV/PAenh] ratio in all patients during both the early and late phases for adjustment of timing.

Results:

The [late-phase lung PBV/PAenh] ratio was 0.092±0.029 in the group with PTE and 0.108±0.030 in the group without PTE, showing a significant difference between the 2 groups (P<0.0001). The [early-phase lung PBV values/PAenh]/[late-phase lung PBV values/PAenh] ratio was 0.68±0.19 and 0.84±0.20, respectively, also showing a significant difference between the 2 groups (P<0.0001). Finally, the [early-phase lung PBV/PAenh]/[late-phase lung PBV/PAenh] ratio was 0.71±0.19 in patients with acute PTE and 0.56±0.16 in patients with chronic PTE, and there was a significant difference between these 2 subgroups (P=0.0004).

Conclusions:

It may be useful to determine late-phase lung PBV values in patients with PTE, because this parameter may reflect the systemic collateral flow, which is increased in chronic PTE.
Minimal Endoscope-assisted Thyroidectomy Through a Retroauricular Approach: An Evolving Solo Surgery Technique
Authors: Ban Myung Jin , Chang Jae Won , Kim Won Shik , Byeon Hyung Kwon , Koh Yoon Woo , Park Jae Hong
Published: November 2016

This study aimed to evaluate the feasibility and efficacy of minimal endoscope-assisted thyroidectomy (MEAT) through a retroauricular (RA) approach. Most of the thyroidectomy operative time was accounted for by direct visualization through the RA window, minimizing interference between surgical instruments. Endoscope use was minimized and limited to critical surgical aspects, including preservation of the recurrent laryngeal nerve and parathyroid glands. The recurrent laryngeal nerve was neuromonitored throughout the procedure. MEAT through an RA approach was performed in 8 patients with papillary thyroid carcinoma (mean tumor size, 1.2±0.5 cm). The mean patient age was 41.1±7.5 years. The endoscopic operating time was 19±3.4 minutes, and no postoperative hematoma, seroma, or vocal cord paralysis was observed. MEAT through an RA approach was feasible and safe. Solo thyroidectomy through the RA approach is possible without depending on an endoscopic view, overcoming limited working space and minimizing instrument interference during endoscopic RA thyroidectomy.
Resilience, Invariability, and Ecological Stability across Levels of Organization
Authors: Haegeman Bart , Arnoldi Jean-François , Wang Shaopeng , de Mazancourt Claire , Montoya José M. , Loreau Michel
Published: November 2016

Ecological stability is a bewildering broad concept. The most common stability measures are asymptotic resilience, widely used in theoretical studies, and measures based on temporal variability, commonly used in empirical studies. We construct measures of invariability, defined as the inverse of variability, that can be directly compared with asymptotic resilience. We show that asymptotic resilience behaves like the invariability of the most variable species, which is often a rare species close to its extinction boundary. Therefore, asymptotic resilience displays complete loss of stability with changes in community composition. In contrast, mean population invariability and ecosystem invariability are insensitive to rare species and quantify stability consistently whether details of species composition are considered or not. Invariability provides a consistent framework to predict diversity-stability relationships that agree with empirical data at population and ecosystem levels. Our findings can enhance the dialogue between theoretical and empirical stability studies.
Genetic overlap between in-scanner head motion and the default network connectivity
Authors: Zhou Yuan , Chen Jie , Luo Yu L.L. , Zheng Dang , Rao Li-Lin , Li Xinying , Zhang Jianxin , Li Shu , Friston Karl , Zuo Xi-Nian
Published: November 2016

The association between in-scanner head motion and intrinsic functional connectivity (iFC) may confound explanations for individual differences in functional connectomics. However, the etiology of the correlation between head motion and iFC has not been established. This study aimed to investigate genetic and environmental contributions on the association between head motion and iFC using a twin dataset (175 same-sex twin pairs, aged 14-23 years, 48% females). After establishing that both head motion and default network iFC are moderately heritable, we found large genetic correlations (-0.52 to -0.73) between head motion and the default network iFCs. Common genes can explain 48% - 61% of the negative phenotypic correlation between the two phenotypes. These results advance our understanding of the relationship between head motion and iFC, and may have profound implications for interpreting individual differences in default network connectivity in clinical research and brain-behavior association.
Genetic variation for mitochondrial function in the New Zealand freshwater snailPotamopyrgus antipodarum
Authors: Sharbrough Joel , Cruise Jennifer L. , Beetch Megan , Enright Nicole M. , Neiman Maurine
Published: November 2016

The proteins responsible for mitochondrial function are encoded by two different genomes with distinct inheritance regimes, rendering rigorous inference of genotype-phenotype connections intractable for all but a few model systems. Asexual organisms provide a powerful means for addressing these challenges because offspring produced without recombination inherit both nuclear and mitochondrial genomes from a single parent. As such, these offspring inherit mitonuclear genotypes that are identical to the mitonuclear genotypes of their parents and siblings and different from those of other asexual lineages. Here, we compared mitochondrial function across distinct asexual lineages ofPotamopyrgus antipodarum,a New Zealand freshwater snail model for understanding the evolutionary consequences of asexuality. Our analyses revealed substantial phenotypic variation across asexual lineages at three levels of biological organization: mitogenomic, organellar, and organismal. These data demonstrate that different asexual lineages have different mitochondrial function phenotypes and that there exists heritable variation (that is, the raw material for evolution) for mitochondrial function inP. antipodarum.The discovery of this variation combined with the methods developed here sets the stage to useP. antipodarumto study central evolutionary questions involving mitochondrial function, including whether mitochondrial mutation accumulation influences the maintenance of sexual reproduction in natural populations.
EMDUNIFRAC: EXACT LINEAR TIME COMPUTATION OF THE UNIFRAC METRIC AND IDENTIFICATION OF DIFFERENTIALLY ABUNDANT ORGANISMS
Authors: McClelland Jason , Koslicki David
Published: November 2016

Both the weighted and unweighted Unifrac distances have been very successfully employed to assess if two communities differ, but do not give any information abouthowtwo communities differ. We take advantage of recent observations that the Unifrac metric is equivalent to the so-calledearth mover’s distance(also known as the Kantorovich-Rubinstein metric) to develop an algorithm that not only computes the Unifrac distance in linear time and space, but also simultaneously finds which operational taxonomic units are responsible for the observed differences between samples. This allows the algorithm, called EMDUnifrac, to determinewhygiven samples are different, not justifthey are different, and with no added computational burden. EMDUnifrac can be utilized on any distribution on a tree, and so is particularly suitable to analyzing both operational taxonomic units derived from amplicon sequencing, as well as community profiles resulting from classifying whole genome shotgun metagenomes. The EMDUnifrac source code (written in python) is freely available at:https://github.com/dkoslicki/EMDUnifrac.
Mathematical models of SIR disease spread with combined non-sexual and sexual transmission routes
Authors: Miller Joel C
Published: November 2016

The emergence of diseases such as Zika and Ebola has highlighted the need to understand the role of sexual transmission in the spread of diseases with a primarily non-sexual transmission route. In this paper we develop a number of low-dimensional models which are appropriate for a range of assumptions for how a disease will spread if it has sexual transmission through a sexual contact network combined with some other transmission mechanism, such as direct contact or vectors. The equations derived provide exact predictions for the dynamics of the corresponding simulations in the large population limit.
Test-retest reliability of functional connectivity networks during naturalistic fMRI paradigms
Authors: Wang Jiahui , Ren Yudan , Hu Xintao , Thai Nguyen Vinh , Guo Lei , Han Junwei , Guo Christine Cong
Published: November 2016

Functional connectivity analysis has become a powerful tool for probing the human brain function and its breakdown in neuropsychiatry disorders. So far, most studies adopted resting state paradigm to examine functional connectivity networks in the brain, thanks to its low demand and high tolerance that are essential for clinical studies. However, the test-retest reliability of resting state connectivity measures is moderate, potentially due to its low behavioral constraint. On the other hand, naturalistic neuroimaging paradigms, an emerging approach for cognitive neuroscience with high ecological validity, could potentially improve the reliability of functional connectivity measures. To test this hypothesis, we characterized the test-retest reliability of functional connectivity measures during a natural viewing condition, and benchmarked it against resting state connectivity measures acquired within the same functional magnetic resonance imaging (fMRI) session. We found that the reliability of connectivity and graph theoretical measures of brain networks is significantly improved during natural viewing conditions over resting state conditions, with an average increase of almost 50% across various connectivity measures. Not only sensory networks for audio-visual processing become more reliable, higher order brain networks, such as default mode and attention networks, also appear to show higher reliability during natural viewing. Our results support the use of natural viewing paradigms in estimating functional connectivity of brain networks, and have important implications for clinical application of fMRI.
Modeling disease spread in populations with birth, death, and concurrency
Authors: Miller Joel C. , Slim Anja C.
Published: November 2016

The existence of sexual partnerships that overlap in time (concurrent relationships) is believed by some to be a significant contributing factor to the spread of HIV, although this is controversial. We derive an analytic model which allows us to investigate and compare disease spread in populations with and without concurrency. We can identify regions of parameter space in which its impact is negligible, and other regions in which it plays a major role. We also see that the impact of concurrency on the initial growth phase can be much larger than its impact on the equilibrium size. We see that the effect of concurrency saturates, which leads to the perhaps surprising conclusion that interventions targeting concurrency may be most effective in populations with low to moderate levels of concurrency.

Author Summary

We consider the spread of an infectious disease through a population modeled by a dynamic network with demographic turnover. We develop a stochastic model of the disease and derive governing equations that exactly predict the large population (deterministic) limit of the stochastic model. We use this to investigate the role of concurrency and find that interventions targeting concurrency may be most effective in populations with lower levels of concurrency.

Our model is not intended to be an accurate representation of any single population. Rather it is intended to give general insights for intervention design and to provide a framework which can be further specialized to particular populations.

This model is the first model to allow for analytic investigation of the impact of concurrent partnerships in a population exhibiting demographic turnover. Thus it will be useful for investigating the “concurrency hypothesis.”
Proteotype profiling unmasks a viral signaling network essential for poxvirus assembly and transcriptional competence
Authors: Novy Karel , Kilcher Samuel , Omasits Ulrich , Ernst Bleck Christopher Karl , Beerli Corina , Syedbasha Mohammedyaseen , Maiolica Alessio , Mercer Jason , Wollscheid Bernd
Published: November 2016

To orchestrate context-dependent signaling programs poxviruses encode two dual-specificity enzymes, the F10 kinase and the H1 phosphatase. These signaling mediators are essential for poxvirus production, yet their substrate profiles and systems level functions remain enigmatic. Using a phosphoproteomic screen of cells infected with wildtype, F10, and H1 mutant viruses we systematically defined the viral signaling network controlled by these enzymes. Quantitative cross-comparison revealed 33 F10 and/or H1 phosphosites within 17 viral proteins. Using this proteotype dataset to inform genotype-phenotype relationships we found that H1-deficient virions harbor a hidden hyper-cleavage phenotype driven by reversible phosphorylation of the virus protease I7 (S134). Quantitative phospho-proteotyping further revealed that the phosphorylation-dependent activity of the viral early transcription factor, A7 (Y367), underlies the transcription-deficient phenotype of H1 mutant virions. Together these results highlight the utility of combining quantitative proteotype screens with mutant viruses to uncover novel proteotype-phenotype-genotype relationships that are masked by classical genetic studies.
Replication fork instability and the consequences of fork collisions from rereplication
Authors: Alexander Jessica L. , Orr-Weaver Terry L.
Published: November 2016

Replication forks encounter obstacles that must be repaired or bypassed to complete chromosome duplication before cell division. Proteomic analysis of replication forks suggests that the checkpoint and repair machinery travels with unperturbed forks, implying that they are poised to respond to stalling and collapse. However, impaired fork progression still generates aberrations, including repeat copy number instability and chromosome rearrangements. Deregulated origin firing also causes fork instability if a newer fork collides with an older one, generating double-strand breaks (DSBs) and partially rereplicated DNA. Current evidence suggests that multiple mechanisms are used to repair rereplication damage, yet these can have deleterious consequences for genome integrity.
Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly
Authors: Xu Chao , Ishikawa Hideaki , Izumikawa Keiichi , Li Li , He Hao , Nobe Yuko , Yamauchi Yoshio , Shahjee Hanief M. , Wu Xian-Hui , Yu Yi-tao , Isobe Toshiaki , Takahashi Nobuhiro , Min Jinrong
Published: November 2016

In cytoplasm, the survival of motor neuron (SMN) complex delivers pre-small nuclear RNAs (pre-snRNAs) to the heptameric Sm ring for the assembly of the ring complex on pre-snRNAs at the conserved Sm site [A(U)4–6G]. Gemin5, a WD40 protein component of the SMN complex, is responsible for recognizing pre-snRNAs. In addition, Gemin5 has been reported to specifically bind to the m7G cap. In this study, we show that the WD40 domain of Gemin5 is both necessary and sufficient for binding the Sm site of pre-snRNAs by isothermal titration calorimetry (ITC) and mutagenesis assays. We further determined the crystal structures of the WD40 domain of Gemin5 in complex with the Sm site or m7G cap of pre-snRNA, which reveal that the WD40 domain of Gemin5 recognizes the Sm site and m7G cap of pre-snRNAs via two distinct binding sites by respective base-specific interactions. In addition, we also uncovered a novel role of Gemin5 in escorting the truncated forms of U1 pre-snRNAs for proper disposal. Overall, the elucidated Gemin5 structures will contribute to a better understanding of Gemin5 in small nuclear ribonucleic protein (snRNP) biogenesis as well as, potentially, other cellular activities.
Challenging the conceptual framework of maintenance hosts for influenza A viruses in wild birds
Authors: Caron Alexandre , Cappelle Julien , Gaidet Nicolas
Published: November 2016

The conceptual framework considering Anseriformes and Charadriiformes as the main maintenance hosts for influenza A viruses (IAV) in wild birds has shaped IAV research and surveillance over the last decades.

We challenge this framework by reviewing the world‐wide surveillance data on non‐Anseriformes and non‐Charadriiformes (NANC) species, generally considered as playing little role in IAV maintenance, available in literature and online data bases (close to 200 sources).

Globally, we found an IAV infection rate of 1·51% (95% CI, 1·44–1·59%) for c. 101 000 birds tested from NANC species. If Anseriformes have, as expected, a higher infection rate than any other bird orders, eight bird orders have an infection rate higher or close to the Charadriiformes infection rate, challenging the status of Charadriiformes.

We interpret the attention paid in favour of Charadriiformes by an extrapolation bias from data collected in hotspots of IAV infection in Charadriiformes (e.g. Delaware Bay, USA).

The growing data on IAV in wild birds world‐wide, summarised here, support two non‐exclusive hypotheses: (i) the quality of the diagnostic tools and techniques used explain the patterns observed; (ii) IAV maintenance is determined by complex multi‐host systems composed of multiple bird species, dependent on the ecosystem and its bird diversity and composition.

Synthesis and applications. Our results have two main implications. First, new research and surveillance should be designed in order to understand influenza A viruses ecology in wild birds across the world, along with appropriate diagnostic tools and new hypotheses and dedicated protocols. This should be done in line with our new conceptual framework that conveys less a priori than its predecessor. Second, our results call for more bridging between biological and epidemiological sciences in order to tackle disease ecology in multi‐host systems.
A cadaver study comparing three fibreoptic‐assisted techniques for converting a supraglottic airway to a cuffed tracheal tube
Authors: Olesnicky B. L. , Rehak A. , Bestic W. B. , Brock J. T. , Watterson L.
Published: November 2016

After rescuing an airway with a supraglottic airway device, a method to convert it to a cuffed tracheal tube is often needed. The best method to do this has never been directly studied. We compared three techniques for conversion of a standard LMA® Unique airway to a cuffed endotracheal tube using a fibrescope. The primary endpoint was time to intubation, with secondary endpoints of success rate, perceived difficulty and preferred technique. We also investigated the relationship between level of training and prior training and experience with the techniques on the primary outcome. The mean (95% CI) time to intubation using a direct tracheal tube technique of 37 (31–42) s was significantly shorter than either the Aintree intubation catheter technique at 70 (60–80) s, or a guidewire technique at 126 (110–141) s (p < 0.001). Most (13/24) participants rated the tracheal tube as their preferred technique, while 11/24 preferred the Aintree technique. In terms of perceived difficulty, 23/24, 21/24 and 9/24 participants rated the tracheal tube technique, Aintree technique and guidewire technique, respectively, as either very easy or easy. There was no relationship between prior training, prior experience or level of training on time to completion of any of the techniques. We conclude the tracheal tube and Aintree techniques both provide a rapid and easy method for conversion of a supraglottic airway device to a cuffed tracheal tube. The guidewire technique cannot be recommended.
Risk stratification: a tool to predict the course of active surveillance for localized prostate cancer?
Authors: Herden Jan , Heidenreich Axel , Weissbach Lothar
Published: November 2016

Objective

To investigate a cohort of patients undergoing active surveillance (AS) for localized prostate cancer (PCa) with regard to possible differences in discontinuation rates, subsequent therapies, reasons for intervention and pathological findings after deferred surgery after patient stratification into very‐low‐risk, low‐risk and intermediate‐/high‐risk PCa groups.

Patients and Methods

The HAROW study was a non‐interventional, observational, outcomes research study on the management of localized PCa in the community setting. A total of 468 patients were prospectively enrolled in the HAROW study, with a mean follow‐up of 28.5 months. Treating urologists reported clinical variables, information on therapy and clinical course of disease at 6‐month intervals.

Results

Of 468 patients under AS, 244 were stratified into very‐low‐risk, 142 into low‐risk and 82 into intermediate‐/high‐risk groups. Of these patients, 112 discontinued AS. Discontinuation rates were 25.4% in the very‐low‐risk, 21.1% in the low‐risk and 24.4% in the intermediate‐/high‐risk groups (P = 0.633). The main reasons for intervention were biopsy upgrade and/or prostate‐specific antigen elevation in the very‐low‐ and low‐risk groups, and patient preference in the intermediate‐/high‐risk group (P < 0.05). No significant differences were found regarding subsequent therapies and pathological findings after deferred surgery.

Conclusion

Our results show no differences in the outcome of risk‐stratified patients in the specified risk groups managed with AS, while switching to an invasive treatment on the patient′s request was more frequent in the intermediate‐/high‐risk group.
Genetic diversity and structure of the Australian flora
Authors: Broadhurst Linda , Breed Martin , Lowe Andrew , Bragg Jason , Catullo Renee , Coates David , Encinas‐Viso Francisco , Gellie Nick , James Elizabeth , Krauss Siegfried , Potts Brad , Rossetto Maurizio , Shepherd Mervyn , Byrne Margaret
Published: November 2016

Aim

To investigate the relationships between species attributes and genetic parameters in Australian plant species and to determine the associations in relation to predictions from population theory and previous global analyses.

Location

Continent of Australia.

Methods

We assembled a dataset of all known population genetic analyses of Australian plants based on neutral markers and catalogued them according to key species attributes, including range, abundance, range disjunction, biome and growth form; and genetic parameters, mean number of alleles per locus, observed and expected heterozygosity and population differentiation. We determined relationships between species attributes and genetic parameters using a maximum‐likelihood, multimodel inference approach.

Results

We found many associations that were consistent with predictions. Species attributes with greatest effect on genetic diversity were range size, growth form, abundance and biome. The most important attributes influencing genetic differentiation were range disjunction and abundance. We found unexpected results in the effects of biome and growth form on genetic diversity, with greater diversity in the eastern biome of Australia, and lower diversity in shrubs compared to trees.

Main conclusions

Our analysis of genetic diversity of Australian plants showed associations consistent with predictions based on population genetics theory, with strong effects of range size, abundance and growth form. We identified a striking effect of range disjunction on population genetic differentiation, an effect that has received little attention in the literature. We also found some notable differences to global predictions, which were most likely explained by confounding effects across variables. This highlights that caution is needed when extrapolating trends from global analyses to regional floras. Identifying associations between species attributes and patterns of genetic diversity enables broadscale predictions to facilitate the inclusion of genetic considerations into conservation decision‐making.
Diabetes incidence and prevalence in Hong Kong, China during 2006–2014
Authors: Quan J. , Li T. K. , Pang H. , Choi C. H. , Siu S. C. , Tang S. Y. , Wat N. M. S. , Woo J. , Johnston J. M. , Leung G. M.
Published: November 2016

Aims

To estimate recent secular changes in the incidence and prevalence of diabetes and pre‐diabetes among Hong Kong Chinese adults, and thus show possible future trends for developing mainland China.

Methods

Based on a complete census of the public sector health records of 6.4 million people from 2006 to 2014, diabetes cases were ascertained using different methods including the World Health Organization (WHO) 2011 guidelines (HbA1c, fasting plasma glucose and glucose tolerance test), American Diabetes Association (ADA) 2015 guidelines (plus random plasma glucose), and additionally recorded diagnosis codes and medication dispensation. Pre‐diabetes was defined using ADA 2015 guidelines.

Results

We identified 697 201 people with diabetes (54.2% were incident cases); and 1 229 731 people with diabetes or pre‐diabetes. In 2014, the overall incidence of diabetes was 9.46 per 1000 person‐years [95% confidence interval (CI): 9.38 to 9.54], and overall prevalence was 10.29% (95% CI: 10.27% to 10.32%). Incidence of diabetes decreased significantly from 2007 to 2014 (quadratic trend, P < 0.001). From 2006 to 2014, the prevalence of diabetes increased significantly in both sexes and across all age groups (quadratic trend, P < 0.001). The overall incidence of pre‐diabetes in 2014 was 18.88 per 1000 person‐years (95% CI: 18.76 to 18.99), and the overall prevalence of pre‐diabetes was 8.90% (95% CI: 8.87% to 8.92%).

Conclusions

Similar to other developed western and Asian populations, diabetes (and pre‐diabetes) incidence in Hong Kong Chinese appeared to have stabilized and there have been small declines during the period of observation. Ageing and survivorship will likely drive a continued increase in the prevalence of diabetes and pre‐diabetes, albeit with a decelerating growth rate if past trends persist.
Reductions in cortical alpha activity, enhancements in neural responses and impaired gap detection caused by sodium salicylate in awake guinea pigs
Authors: Berger Joel I. , Coomber Ben , Wallace Mark N. , Palmer Alan R.
Published: November 2016

Tinnitus chronically affects between 10–15% of the population but, despite its prevalence, the underlying mechanisms are still not properly understood. One experimental model involves administration of high doses of sodium salicylate, as this is known to reliably induce tinnitus in both humans and animals. Guinea pigs were implanted with chronic electrocorticography (ECoG) electrode arrays, with silver‐ball electrodes placed on the dura over left and right auditory cortex. Two more electrodes were positioned over the cerebellum to monitor auditory brainstem responses (ABRs). We recorded resting‐state and auditory evoked neural activity from awake animals before and 2 h following salicylate administration (350 mg/kg; i.p.). Large increases in click‐evoked responses (> 100%) were evident across the whole auditory cortex, despite significant reductions in wave I ABR amplitudes (in response to 20 kHz tones), which are indicative of auditory nerve activity. In the same animals, significant decreases in 6–10 Hz spontaneous oscillations (alpha waves) were evident over dorsocaudal auditory cortex. We were also able to demonstrate for the first time that cortical evoked potentials can be inhibited by a preceding gap in background noise [gap‐induced pre‐pulse inhibition (PPI)], in a similar fashion to the gap‐induced inhibition of the acoustic startle reflex that is used as a behavioural test for tinnitus. Furthermore, 2 h following salicylate administration, we observed significant deficits in PPI of cortical responses that were closely aligned with significant deficits in behavioural responses to the same stimuli. Together, these data are suggestive of neural correlates of tinnitus and oversensitivity to sound (hyperacusis).
Microphthalmia‐associated transcription factor ensures the elongation of axons and dendrites in the mouse frontal cortex
Authors: Ohba Koji , Takeda Kazuhisa , Furuse Tamio , Suzuki Tomohiro , Wakana Shigeharu , Suzuki Takashi , Yamamoto Hiroaki , Shibahara Shigeki
Published: November 2016

Long interspersed element‐1 (LINE‐1) is a mammalian transposable element, and its genomic insertion could cause neurological disorders in humans. Incidentally, LINE‐1 is present in intron 3 of the microphthalmia‐associated transcription factor (Mitf) gene of the black‐eyed white mouse (Mitfmi‐bw allele). Mice homozygous for the Mitfmi‐bw allele show the white coat color with black eye and deafness. Here, we explored the functional consequences of the LINE‐1 insertion in the Mitf gene using homozygous Mitfmi‐bw mice on the C3H background (C3H‐bw mice) or on the C57BL/6 background (bw mice). The open‐field test showed that C3H‐bw mice moved more irregularly in an unfamiliar environment during the 20‐min period, compared to wild‐type mice, suggesting the altered emotionality. Moreover, C3H‐bw mice showed the lower serum creatinine levels, which may reflect the creatine deficiency. In fact, morphologically abnormal neurons and astrocytes were detected in the frontal cortex of bw mice. The immunohistochemical analysis of bw mouse tissues showed the lower intensity for expression of guanidinoacetate methyltransferase, a key enzyme in creatine synthesis, in neurons of the frontal cortex and in glomeruli and renal tubules. Thus, Mitf may ensure the elongation of axons and dendrites by maintaining creatine synthesis in the frontal cortex.