bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the subtle signatures of feedback from distant AGN using ALMA observations and the EAGLE hydrodynamical simulations
Authors: Scholtz J , Alexander D M , Harrison C M , Rosario D J , McAlpine S , Mullaney J R , Stanley F , Simpson J , Theuns T , Bower R G , Hickox R C , Santini P , Swinbank A M
Published: December 2017

We present sensitive 870 μm continuum measurements from our ALMA programmes of 114 X-ray selected active galactic nuclei (AGN) in the Chandra Deep Field-South and Cosmic Evolution Survey fields. We use these observations in combination with data from Spitzer and Herschel to construct a sample of 86 X-ray selected AGN, 63 with ALMA constraints at z = 1.5–3.2 with stellar mass >2 × 1010 M⊙. We constructed broad-band spectral energy distributions in the infrared band (8–1000 μm) and constrain star-formation rates (SFRs) uncontaminated by the AGN. Using a hierarchical Bayesian method that takes into account the information from upper limits, we fit SFR and specific SFR (sSFR) distributions. We explore these distributions as a function of both X-ray luminosity and stellar mass. We compare our measurements to two versions of the Evolution and Assembly of GaLaxies and their Environments (EAGLE) hydrodynamical simulations: the reference model with AGN feedback and the model without AGN. We find good agreement between the observations and that predicted by the EAGLE reference model for the modes and widths of the sSFR distributions as a function of both X-ray luminosity and stellar mass; however, we found that the EAGLE model without AGN feedback predicts a significantly narrower width when compared to the data. Overall, from the combination of the observations with the model predictions, we conclude that (1) even with AGN feedback, we expect no strong relationship between the sSFR distribution parameters and instantaneous AGN luminosity and (2) a signature of AGN feedback is a broad distribution of sSFRs for all galaxies (not just those hosting an AGN) with stellar masses above ≈1010 M⊙.
Ranking Quantitative Resistance to Septoria tritici Blotch in Elite Wheat Cultivars Using Automated Image Analysis
Authors: Karisto Petteri , Hund Andreas , Yu Kang , Anderegg Jonas , Walter Achim , Mascher Fabio , McDonald Bruce A. , Mikaberidze Alexey
Published: December 2017

Quantitative resistance is likely to be more durable than major gene resistance for controlling Septoria tritici blotch (STB) on wheat. Earlier studies hypothesized that resistance affecting the degree of host damage, as measured by the percentage of leaf area covered by STB lesions, is distinct from resistance that affects pathogen reproduction, as measured by the density of pycnidia produced within lesions. We tested this hypothesis using a collection of 335 elite European winter wheat cultivars that was naturally infected by a diverse population of Zymoseptoria tritici in a replicated field experiment. We used automated image analysis of 21,420 scanned wheat leaves to obtain quantitative measures of conditional STB intensity that were precise, objective, and reproducible. These measures allowed us to explicitly separate resistance affecting host damage from resistance affecting pathogen reproduction, enabling us to confirm that these resistance traits are largely independent. The cultivar rankings based on host damage were different from the rankings based on pathogen reproduction, indicating that the two forms of resistance should be considered separately in breeding programs aiming to increase STB resistance. We hypothesize that these different forms of resistance are under separate genetic control, enabling them to be recombined to form new cultivars that are highly resistant to STB. We found a significant correlation between rankings based on automated image analysis and rankings based on traditional visual scoring, suggesting that image analysis can complement conventional measurements of STB resistance, based largely on host damage, while enabling a much more precise measure of pathogen reproduction. We showed that measures of pathogen reproduction early in the growing season were the best predictors of host damage late in the growing season, illustrating the importance of breeding for resistance that reduces pathogen reproduction in order to minimize yield losses caused by STB. These data can already be used by breeding programs to choose wheat cultivars that are broadly resistant to naturally diverse Z. tritici populations according to the different classes of resistance.
Isolated Absent Thelarche in a Patient With Neurofibromatosis Type 1 and Acromegaly
Authors: Martini Anne E. , Zolton Jessica R. , DeCherney Alan H.
Published: December 2017

BACKGROUND:

Isolated absent thelarche is a rare condition that is infrequently reviewed in the literature.

CASE:

A 28-year-old woman with neurofibromatosis type 1 and acromegaly presented with absent breast development despite hormone therapy. Examination noted a normally developed woman with acromegalic features and Tanner stage I breasts. Hormone studies and karyotype were normal. Magnetic resonance imaging of the patient's brain demonstrated a voluminous pituitary. Chromosome microarray analysis diagnosed the neurofibromatosis 1 microdeletion syndrome. Breast ultrasonography and surgical consultation were offered.

CONCLUSIONS:

Neither neurofibromatosis type 1, acromegaly, nor neurofibromatosis 1 microdeletion syndrome are linked to absent thelarche. After attempting hormone therapy, patients with absent thelarche should be evaluated for congenital breast anomalies, estrogen receptor abnormalities, or gene defects. Psychological and surgical consultation should also be offered.
Intrauterine Balloon Tamponade for Severe Postpartum Hemorrhage
Authors: Revert Mathilde , Rozenberg Patrick , Cottenet Jonathan , Quantin Catherine
Published: December 2017

OBJECTIVE:

To compare the rates of invasive procedures (surgical or vascular) for hemorrhage control between a perinatal network that routinely used intrauterine balloon tamponade and another perinatal network that did not in postpartum hemorrhage management.

METHODS:

This population-based retrospective cohort study included all women (72,529) delivering between 2011 and 2012 in the 19 maternity units in two French perinatal networks: a pilot (in which balloon tamponade was used) and a control network. Outcomes were assessed based on discharge abstract data from the national French medical information system. General and obstetric characteristics were included in two separate multivariate logistic models according to the mode of delivery (vaginal and cesarean) to estimate the independent association of the network with invasive procedures.

RESULTS:

Invasive procedures (pelvic vessel ligation, arterial embolization, hysterectomy) were used in 298 women and in 4.1 per 1,000 deliveries (95% CI 3.7–4.6). The proportion of women with at least one invasive procedure was significantly lower in the pilot network (3.0/1,000 vs 5.1/1,000, P<.01). Among women who delivered vaginally, the use of arterial embolization was also significantly lower in the pilot than the control network (0.2/1,000 vs 3.7/1,000, P<.01) as it was for those who delivered by cesarean (1.3/1,000 vs 5.7/1,000, P<.01). After controlling for potential confounding factors, the risk of an invasive procedure among women who delivered vaginally remained significantly lower in the pilot network (adjusted odds ratio [OR] 0.14, 95% CI 0.08–0.27), but not for women who delivered by cesarean (adjusted OR 1.19, 95% CI 0.87–1.61).

CONCLUSION:

The use of intrauterine balloon tamponade in routine clinical practice was associated with a significantly lower use of invasive procedures for hemorrhage control among women undergoing vaginal delivery.
Achieving High Reliability Through Cultural Mindfulness
Authors: Cawley Patrick J. , Scheurer Danielle B.
Published: December 2017

Healthcare has enthusiastically embraced quality and safety improvement. Yet, more radical transformation is clearly needed to make a more significant impact on error reduction and to ensure consistent quality. This need for transformation is leading healthcare to examine how other industries, such as nuclear power and aviation, improve safety to achieve a high degree of reliability and avoid potential catastrophes. Research has shown that successful organizations in high-risk industries achieve high reliability by maintaining a cultural mindfulness that allows them to continually reinvent themselves in complex environments. Healthcare faces similar challenges and could greatly benefit from instilling high-reliability principles in its operations. The Medical University of South Carolina, an academic health system, has been on a quest to improve safety and quality by implementing a high-reliability culture.
High-Reliability Principles Must Be Tied to Value-Based Outcomes
Authors: Wasden Mitchell L.
Published: December 2017

WellStar Health System and the Medical University of South Carolina (MUSC), highlighted in this issue’s feature articles, are two organizations seeking to drive high reliability by educating leaders and incorporating high-reliability principles into their quality improvement (QI) efforts. The organizations have taken slightly different approaches to executing on high reliability, yet both are encouraged by the apparent success of high-reliability principles in other industries.

The high-reliability framework is often applied to healthcare despite the limitations of comparing healthcare organizations to nuclear reactors, commercial airlines, and aircraft carriers. Notably, these industries were classified as “highly reliable” after the fact, meaning their employees and leadership already had existing routines and qualities that researchers would describe, after direct observation, as a shared distinguishing feature. Thus, in contrast to Lean, Six Sigma, and other QI movements that have been applied in healthcare, industries such as nuclear power and aviation came with tools and quantitative processes already embedded. The high-reliability framework is qualitative, while the actual hard, quantitative tools and processes differ by industry. This fact makes adopting high-reliability principles difficult because the tools must be created and scaled for each industry. Healthcare is still in the early stages of building these tools to support the high-reliability framework, and the articles by Saunders and Brennan (at WellStar) and Cawley and Scheurer (at MUSC) describe early attempts to provide insights into launching high-reliability principles and tools in healthcare.

High reliability is a theoretical construct that is difficult to implement without a concrete framework for execution. The five characteristics that frame a high-reliability organization (HRO), as outlined by Cawley and Scheurer (citing Weick and Sutcliffe 2001), are (1) preoccupation with failure, (2) reluctance to simplify interpretations, (3) sensitivity to operations, (4) commitment to resilience, and (5) deference to expertise. Although these elements point in the right direction, they remain theoretical if not tethered to an organization’s operating cycle.
Remaining Financially Viable in a Time of Healthcare Transition
Authors: Ronan Barry P.
Published: December 2017

In an unstable healthcare environment, Western Maryland Health System has been demonstrating stability. We have responded to the many challenges that hospitals face and managed to thrive in the new, value-based world.

We made the transition to value-based payment and care delivery models through innovations in Maryland’s payment system. In 2010, we recognized that becoming a demonstration project for value-based care would benefit our health system as we dealt with an aging and shrinking regional population. By moving care away from the acute setting to other settings across the care continuum, we now treat patients in the most appropriate setting (e.g., the home, physician office, clinic, and even senior centers, churches, and homeless shelters).

As we have transitioned care, we have also transitioned our workforce. With fewer acute care patients, we need fewer staff members at the bedside. Many of our staff have shifted to delivering care in pre- and post-acute care settings.

To improve our financial performance, we formed an alliance of three health systems. This new alliance has found increased savings by consolidating services, managing regionwide population health initiatives, and benchmarking clinical quality through best practices. Through the alliance, each individual health system is stronger and well augmented by the savings that it could not achieve separately.

The transition has not been easy, but we have shown that it is achievable. We have identified a number of solutions to reduce costs and generate savings while enhancing quality and patient safety. These solutions may present a pathway to success for other organizations seeking to move to value-based care delivery and new payment models.
SURGICAL REMOVAL OF EPIRETINAL MEMBRANE WITH AND WITHOUT REMOVAL OF INTERNAL LIMITING MEMBRANE
Authors: De Novelli Fernando J. , Goldbaum Mauro , Monteiro Mario L. R. , Bom Aggio Fabio , Takahashi Walter Y.
Published: December 2017

Purpose:

To study and compare visual acuity, foveal thickness, outer limiting layer, ellipsoid zone, and recurrence rate in patients undergoing removal of the epiretinal membrane with and without the removal of the internal limiting membrane (ILM).

Methods:

Sixty-three patients who had the epiretinal membrane removed by a single surgeon were randomly assigned into 2 groups: Group 1 without additional removal of the ILM and Group 2 with removal of the ILM. Patients were followed up and evaluated at the first month, third month, and sixth month, postoperatively.

Results:

Patients from both groups had a gradual improvement in their vision over time. There was no significant difference in the improvement in visual acuity between the two groups. About tomographic assessment of alterations, no significant differences were found between the groups; however, Group 1 had a higher relapse rate (17%) compared with Group 2 (3.6%) (P = 0.09).

Conclusion:

Epiretinal membrane removal with and without ILM peeling shows similar functional and anatomical improvements, but the group in which the ILM was not removed seemed to have a higher recurrence rate.
BILATERAL UVEAL METASTASES SECONDARY TO PROSTATE ADENOCARCINOMA
Authors: Cochran Katherine J. , Gray James R. , Meluch Anthony A. , Reichstein David A.
Published: December 2017

Purpose:

To report a patient with bilateral uveal metastases secondary to previously quiescent prostate adenocarcinoma with a 22-month follow-up.

Methods:

Retrospective chart review was performed for this patient.

Results:

Androgen deprivation therapy and external beam radiation therapy were shown to manage ocular symptoms in a sixty-nine-year-old man previously diagnosed with adenocarcinoma of the prostate.

Conclusion:

Uveal metastases can be the first site of systemic metastasis even long after initial diagnosis and treatment of prostate adenocarcinoma; the 17 years between this patient's treatment for adenocarcinoma and commencement of his ocular symptoms is the longest interval reported. Hormonal therapy, in conjunction with radiation therapy, can successfully reduce tumor burden in these patients and improve visual symptoms over time.
Visual Outcomes and Aberrometric Changes With Topography-Guided Photorefractive Keratectomy Treatment of Irregular Astigmatism After Penetrating Keratoplasty
Authors: Bandeira e Silva Francisco , Hazarbassanov Rossen Mihaylov , Martines Eduardo , Güell José Luis , Hofling-Lima Ana L.
Published: December 2017

Purpose:

To evaluate the visual acuity and keratometric and aberrometric changes in patients with corneal transplants (PKP), who underwent topography-guided photorefractive keratectomy (TG-PRK) with mitomycin C (MMC).

Methods:

In this case study, 15 patients with spherical equivalents ranging from −11.00 to −0.25 diopters (D) who underwent penetrating corneal transplantation and had irregular astigmatism ranging from −7.5 to −2.0 D underwent TG-PRK with MMC. Corneal topography and wavefront of all patients were measured preoperatively and 12 months postoperatively.

Results:

Twelve months after TG-PRK with MMC, 46% of eyes achieved a best spectacle-corrected visual acuity (BSCVA) of 20/20 compared with 1 eye preoperatively (P = 0.0221, χ2 test). The BSCVA did not improve in 1 patient and increased by 1 line or more in all others. Astigmatism decreased significantly (P = 0.003) from 5.10 ± 0.4 D to 3.37 ± 0.06 D, the corneal best-fit sphere increased and keratometry measurements flattened significantly (P = 0.0001 for both comparisons), and the corneal total root mean square aberrations and trefoil decreased significantly (P = 0.0077 and P = 0.0054, respectively) from 9.11 ± 2.56 μm to 7.58 ± 3.15 μm and 2.00 ± 1.2 to 1.38 ± 0.27 μm, respectively, as measured by wavefront aberrometry.

Conclusions:

Twelve months postoperatively, the BSCVA improved significantly, the lines of vision increased, and astigmatism, corneal best-fit sphere, mean keratometry, corneal thickness, corneal root mean square total, and corneal spherical aberrations decreased. TG-PRK with MMC is a good alternative for correcting post-PKP cases with irregular astigmatism with elevated higher-order aberrations.
Vats Plication of the Diaphragm a Descriptive Observational 10-Year Southampton Experience
Authors: Taberham Rhona J. , Raza Adnan , Alzetani Aiman , Woo Edwin B. , Chamberlain Martin H. , Koulaxouzidis George , Amer Khalid M.
Published: December 2017

Objective

The aim of the study was to report the safety and efficacy of video-assisted thoracoscopic (VATS) plication of the diaphragm at our institution between 2006 and 2016.

Methods

Adult patients selected on etiology and combination of investigations including plain chest x-ray, computed tomography of chest and abdomen, lung functions in supine and sitting positions, radiological/ultrasonic screening for diaphragmatic movement, and phrenic nerve conduction studies. We incorporated a triportal VATS and Endostitch device for plication, using CO2 insufflation to maximum 12 mm Hg. Bilateral simultaneous plication and high-risk patients were electively admitted to intensive therapy unit postoperatively.

Results

Thirty-five patients (24 males) had their diaphragm plicated. The mean age was 56.6 years (range = 23–76 years). The mean body mass index was 32.1 (range = 22.2–45.4). Twenty one were right, 13 left, 2 patients had VATS simultaneous bilateral plication, and 1 had sequential VATS bilateral plication. Paralysis was idiopathic in 17, posttraumatic in 5, postremoval of mediastinal tumor in 4, and postcardiac surgery in 3. All patients presented with lifestyle-limiting dyspnea and orthopnea, three were on nocturnal noninvasive ventilation. Five were diabetic and 16 were smokers. The mean supine forced expiratory volume in the first second was 62.5% of predicted. Twenty two were performed by VATS (63%), three converted to thoracotomy, and 13 were open limited thoracotomy (historic). The mean hospital stay was 4.5 days (range = 1–18, mode 2 days). Intensive therapy unit admission was required in six patients for mechanical ventilation 0 to 3 days. Five patients (14%) had no improvement in symptoms. There were no deaths, no 30-day readmissions, and no long-term neuralgia in this series.

Conclusions

We found minimal access VATS plication of the diaphragm to be feasible and safe, but no firm conclusions should be drawn from our limited resources. We report the feasibility of concomitant bilateral VATS plication of the diaphragm in two adults, and this was not previously reported in the adult population. There is a need for further good quality, prospective studies, and randomized controlled studies evaluating efficacy of VATS diaphragmatic plication.
Thrombotic Thrombocytopenic Purpura in a Child Treated for Acute Lymphoblastic Leukemia: Case Report and Review of Literature
Authors: De Leonardis Francesco , Koronica Roberta , Daniele Rosa Maria , Santoro Nicola
Published: December 2017

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by deficiency of von Willebrand factor–cleaving protease ADAMTS13. Large von Willebrand multimer formation and intravascular platelet aggregation affecting the arterioles and capillaries can result in death unless early treatment is administered. We report on the case of a child with TTP associated with a human herpes virus type-6 infection occurring during chemotherapy for acute lymphoblastic leukemia who was effectively treated by fresh frozen plasma infusions and antiviral therapy. Although rarely observed in children affected by acute lymphoblastic leukemia, TTP is a potentially fatal illness that should be considered in the differential diagnosis of thrombocytopenia with hemolytic anemia.
Associations of Positive Affect and Negative Affect With Allostatic Load: A Lifelines Cohort Study
Authors: Schenk Hendrika M. , Jeronimus Bertus F. , van der Krieke Lian , Bos Elisabeth H. , de Jonge Peter , Rosmalen Judith G.M.
Published: December 2017

Objective

Allostatic load (AL) reflects the deteriorating influences of stress on the body and comprises a selection of biological markers. AL is associated with negative life events, stress, and negative affect (NA), as well as poor health outcomes. However, whether AL is also associated with positive affect (PA) is not clear. The present study therefore explores the association between PA and AL, accounting for age, sex, NA, and health behaviors.

Methods

Data of 45,225 individuals from the first wave of the multidisciplinary prospective population-based cohort study Lifelines were used. AL was operationalized as the sum of 12 inflammatory, cardiovascular, and metabolic markers. The association between PA and AL was tested in a cross-sectional study design using multiple linear regression analysis, adjusting for NA, confounders, and health behaviors. In addition, we explored whether the relation was moderated by age, sex, and NA.

Results

The AL profile was inversely associated with PA (B = −0.083, p < .001) when adjusted for NA, age, and sex. The association between AL and PA remained significant after adjusting for health behaviors (B = −0.076, p < .001). A significant moderating effect was found for sex (PA by sex: B = 0.046, p = .001), indicating that the association between PA and AL was stronger in women than in men.

Conclusions

PA was associated with a more favorable AL profile, especially in women. These results add to the evidence that PA might be of relevance to the etiology of disease.
Sepsis Induces Adipose Tissue Browning in Nonobese Mice But Not in Obese Mice
Authors: Ayalon Itay , Shen Hui , Williamson Lauren , Stringer Keith , Zingarelli Basilia , Kaplan Jennifer M.
Published: December 2017

Severe sepsis and septic shock are the biggest cause of mortality in critically ill patients. Obesity today is one of the world's greatest health challenges. Little is known about the extent of involvement of the white adipose tissue (WAT) in sepsis and how it is being modified by obesity. We sought to explore the involvement of the WAT in sepsis. We hypothesize that sepsis induces browning of the WAT and that obesity alters the response of WAT to sepsis. Six-week-old C57BL/6 mice were randomized to a high-fat diet to induce obesity (obese group) or control diet (nonobese group). After 6 to 11 weeks of feeding, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Mice were sacrificed at 0, 18, and 72 h after CLP and epididymal WAT (eWAT), inguinal WAT, and brown adipose tissue (BAT) harvested. Both types of WAT were processed for light microscopy and transmission electron microscopy to assess for morphological changes in both obese and nonobese mice. Tissues were processed for immunohistochemistry, image analyses, and molecular analyses. BATs were used as a positive control. Nonobese mice have an extensive breakdown of the unilocular lipid droplet and smaller adipocytes in WAT compared with obese mice after sepsis. Neutrophil infiltration increases in eWAT in nonobese mice after sepsis but not in obese mice. Nonobese septic mice have an increase in mitochondrial density compared with obese septic mice. Furthermore, nonobese septic mice have an increase in uncoupling protein-1 expression. Although the WAT of nonobese mice have multiple changes characteristic of browning during sepsis, these changes are markedly blunted in obesity.
A Novel Perfusion System for Damage Control of Hyperkalemia in Swine
Authors: Hoareau Guillaume L. , Kashtan Harris , Walker Lauren E. , Beyer Carl , Wishy Andrew , Grayson J. Kevin , Ross James D. , Stewart Ian J.
Published: December 2017

Introduction:

The standard of care for refractory hyperkalemia is renal replacement therapy (RRT). However, traditional RRT requires specialized equipment, trained personnel, and large amounts of dialysate. It is therefore poorly suited for austere environments. We hypothesized that a simplified hemoperfusion system could control serum potassium concentration in a swine model of acute hyperkalemia.

Methods:

Ten pigs were anesthetized and instrumented. A dialysis catheter was inserted. After bilateral nephrectomy, animals received intravenous potassium chloride and were randomized to the control or treatment group. In both groups, blood was pumped through an extracorporeal circuit (EC) with an in-line hemodialyzer. In the treatment arm, ultrafiltrate from the hemodialyzer was diverted through cartridges containing novel potassium binding beads and returned to the EC. Blood samples were obtained every 30 min for 6 h.

Results:

Serum potassium concentration was significantly lower in the treatment than in the control group over time (P = 0.02). There was no difference in serum total calcium concentration for group or time (P = 0.13 and 0.44, respectively) or platelet count between groups or over time (P = 0.28 and 1, respectively). No significant EC thrombosis occurred. Two of five animals in the control group and none in the treatment group developed arrhythmias. All animals survived until end of experiment.

Conclusions:

A simplified hemoperfusion system removed potassium in a porcine model. In austere settings, this system could be used to temporize patients with hyperkalemia until evacuation to a facility with traditional RRT.
Adaptation in response to environmental unpredictability
Authors: Franch-Gras Lluis , García-Roger Eduardo M. , Serra Manuel , José Carmona María
Published: December 2017

Understanding how organisms adaptively respond to environmental fluctuations is a fundamental question in evolutionary biology. The Mediterranean region typically exhibits levels of environmental unpredictability that vary greatly in habitats over small geographical scales. In cyclically parthenogenetic rotifers, clonal proliferation occurs along with occasional bouts of sex. These bouts contribute to the production of diapausing eggs, which allows survival between growing seasons. Here, we studied two diapause-related traits in rotifers using clones from nineBrachionus plicatilisnatural populations that vary in the degree of environmental unpredictability. We tested the hypothesis that the level of environmental unpredictability is directly related to the propensity for sex and inversely related to the hatching fraction of diapausing eggs. We found significant levels of genetic variation within populations for both traits. Interestingly, a positive correlation between pond unpredictability—quantified in a previous study from satellite imagery—and the propensity for sex was found. This correlation suggests a conservative, bet-hedging strategy that provides protection against unexpectedly short growing seasons. By contrast, the hatching fraction of diapausing eggs was not related to the level of environmental predictability. Our results highlight the ability of rotifer populations to locally adapt to time-varying environments, providing an evolutionarily relevant step forward in relating life-history traits to a quantitative measure of environmental unpredictability.
The persistence of multiple strains of avian influenza in live bird markets
Authors: Pinsent Amy , Pepin Kim M. , Zhu Huachen , Guan Yi , White Michael T. , Riley Steven
Published: December 2017

Multiple subtypes of avian influenza (AI) and novel reassortants are frequently isolated from live bird markets (LBMs). However, our understanding of the drivers of persistence of multiple AI subtypes is limited. We propose a stochastic model of AI transmission within an LBM that incorporates market size, turnover rate and the balance of direct versus environmental transmissibility. We investigate the relationship between these factors and the critical community size (CCS) for the persistence of single and multiple AI strains within an LBM. We fit different models of seeding from farms to two-strain surveillance data collected from Shantou, China. For a single strain and plausible estimates for continuous turnover rates and transmissibility, the CCS was approximately 11 800 birds, only a 4.2% increase in this estimate was needed to ensure persistence of the co-infecting strains (two strains in a single host). Precise values of CCS estimates were sensitive to changes in market turnover rate and duration of the latent period. Assuming a gradual daily sell rate of birds the estimated CCS was higher than when an instantaneous selling rate was assumed. We were able to reproduce prevalence dynamics similar to observations from a single market in China with infection seeded every 5–15 days, and a maximum non-seeding duration of 80 days. Our findings suggest that persistence of co-infections is more likely to be owing to sequential infection of single strains rather than ongoing transmission of both strains concurrently. In any given system for a fixed set of ecological and epidemiological conditions, there is an LBM size below which the risk of sustained co-circulation is low and which may suggest a clear policy opportunity to reduce the frequency of influenza co-infection in poultry.
Intraspecific and interspecific variation in thermotolerance and photoacclimation in
Symbiodinium
dinoflagellates
Authors: Díaz-Almeyda Erika M. , Prada C. , Ohdera A. H. , Moran H. , Civitello D. J. , Iglesias-Prieto R. , Carlo T. A. , LaJeunesse T. C. , Medina M.
Published: December 2017

Light and temperature are major drivers in the ecology and biogeography of symbiotic dinoflagellates living in corals and other cnidarians. We examined variations in physiology among 11 strains comprising five species of clade A
Symbiodinium
. We grew cultures at 26°C (control) and 32°C (high temperature) over a duration of 18 days while measuring growth and photochemical efficiency (

F
v

/

F
m

). Responses to thermal stress ranged from susceptible to tolerant across species and strains. Most strains exhibited a decrease in cell densities and

F
v

/

F
m

when grown at 32°C. Tolerance to high temperature (
T
32
) was calculated for all strains, ranging from 0 (unable to survive at high temperature) to 1 (able survive at high temperature). There was substantial variation in thermotolerance across species and among strains. One strain had a
T
32
close to 1, indicating that growth was not reduced at 32°C for only this one strain. To evaluate the combined effect of temperature and light on physiological stress, we selected three strains with different levels of thermotolerance (tolerant, intermediate and susceptible) and grew them under five different light intensities (65, 80, 100, 240 and 443 µmol quanta m
−2
s
−1
) at 26 and 32°C. High irradiance exacerbated the effect of high temperature, particularly in strains from thermally sensitive species. This work further supports the recognition that broad physiological differences exist not only among species within
Symbiodinium
clades, but also among strains within species demonstrating that thermotolerance varies widely between species and among strains within species.
Coral calcification mechanisms facilitate adaptive responses to ocean acidification
Authors: Schoepf Verena , Jury Christopher P. , Toonen Robert J. , McCulloch Malcolm T.
Published: December 2017

Ocean acidification (OA) is a pressing threat to reef-building corals, but it remains poorly understood how coral calcification is inhibited by OA and whether corals could acclimatize and/or adapt to OA. Using a novel geochemical approach, we reconstructed the carbonate chemistry of the calcifying fluid in two coral species using both a pH and dissolved inorganic carbon (DIC) proxy (δ
11
B and B/Ca, respectively). To address the potential for adaptive responses, both species were collected from two sites spanning a natural gradient in seawater pH and temperature, and then subjected to three pH
T
levels (8.04, 7.88, 7.71) crossed by two temperatures (control, +1.5°C) for 14 weeks. Corals from the site with naturally lower seawater pH calcified faster and maintained growth better under simulated OA than corals from the higher-pH site. This ability was consistently linked to higher pH yet lower DIC values in the calcifying fluid, suggesting that these differences are the result of long-term acclimatization and/or local adaptation to naturally lower seawater pH. Nevertheless, all corals elevated both pH and DIC significantly over seawater values, even under OA. This implies that high pH upregulation combined with moderate levels of DIC upregulation promote resistance and adaptive responses of coral calcification to OA.
Individualized connectome-targeted transcranial magnetic stimulation for neuropsychiatric sequelae of repetitive traumatic brain injury in a retired NFL player
Authors: Siddiqi Shan H. , Trapp Nicholas T. , Shahim Pashtun , Hacker Carl D. , Laumann Timothy O. , Kandala Sridhar , Carter Alexandre R. , Brody David L.
Published: December 2017

The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial inter-individual variability in anatomical localization of brain networks identified using resting-state functional MRI (rsfMRI). Such variability may be particularly important after repetitive traumatic brain injury (TBI), which is associated with treatment-resistant depression. RSNM enables personalized targeting of repetitive transcranial magnetic stimulation (rTMS), a focal brain stimulation technique that relieves depression when administered over dorsolateral prefrontal cortex.

RSNM was used to identify left/right dorsolateral prefrontal rTMS targets with maximal difference between dorsal attention network and default mode network (DMN) correlations. These targets were spatially distinct from those identified by prior methods. The method was evaluated by administering twenty sessions of left-sided excitatory and right-sided inhibitory rTMS to a retired NFL defensive lineman with progressive treatment-resistant neuropsychiatric disturbances. Treatment led to improvement in Montgomery-Asberg Depression Rating Scale (72%), cognitive testing, and headache scales. In comparison with healthy individuals and subjects with TBI-associated depression, baseline rsfMRI revealed substantially elevated DMN connectivity with medial temporal lobe (MTL). Serial rsfMRI scans showed gradual improvement in MTL-DMN connectivity and stimulation site connectivity with subgenual anterior cingulate cortex. This highlights the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.
Improved genome assembly and annotation for the rock pigeon (Columba livia)
Authors: Holt Carson , Campbell Michael , Keays David A. , Edelman Nathaniel , Kapusta Aurélie , Maclary Emily , Domyan Eric , Suh Alexander , Warren Wesley C. , Yandell Mark , Gilbert M. Thomas P. , Shapiro Michael D.
Published: December 2017

The domestic rock pigeon (Columba livia) is among the most widely distributed and phenotypically diverse avian species. This species is broadly studied in ecology, genetics, physiology, behavior, and evolutionary biology, and has recently emerged as a model for understanding the molecular basis of anatomical diversity, the magnetic sense, and other key aspects of avian biology. Here we report an update to the C. livia genome reference assembly and gene annotation dataset. Greatly increased scaffold lengths in the updated reference assembly, along with an updated annotation set, provide improved tools for evolutionary and functional genetic studies of the pigeon, and for comparative avian genomics in general.
Subtle perturbations of the maize methylome reveal genes and transposons silenced by DNA methylation
Authors: Anderson Sarah N. , Zynda Greg , Song Jawon , Han Zhaoxue , Vaughn Matthew , Li Qing , Springer Nathan M.
Published: December 2017

DNA methylation is a chromatin modification that can provide epigenetic regulation of gene and transposon expression. Plants utilize several pathways to establish and maintain DNA methylation in specific sequence contexts. The chromomethylase (CMT) genes maintain CHG (where H = A, C or T) methylation. The RNA-directed DNA methylation (RdDM) pathway is important for CHH methylation. Transcriptome analysis was performed in a collection ofZea mayslines carrying mutant alleles for CMT or RdDM-associated genes. While the majority of the transcriptome was not affected, we identified sets of genes and transposon families sensitive to context-specific decreases in DNA methylation in mutant lines. Many of the genes that are up-regulated in CMT mutant lines have high levels of CHG methylation, while genes that are differentially expressed in RdDM mutants are enriched for having nearby mCHH islands, providing evidence that context-specific DNA methylation directly regulates expression of a small number of genes. The analysis of a diverse set of inbred lines revealed that many genes regulated by CMTs exhibit natural variation for DNA methylation and gene expression. Transposon families with differential expression in the mutant genotypes show few defining features, though several families up-regulated in RdDM mutants show enriched expression in endosperm, highlighting the importance for this pathway during reproduction. Taken together, our findings suggest that while the number of genes and transposon families whose expression is reproducibly affected by mild perturbations in context-specific methylation is small, there are distinct patterns for loci impacted by RdDM and CMT mutants.
Infino: a Bayesian hierarchical model improves estimates of immune infiltration into tumor microenvironment
Authors: Zaslavsky Maxim , Novik Jacqueline Buros , Chang Eliza , Hammerbacher Jeffrey
Published: December 2017

Robust quantification of immune cell infiltration into the tumor microenvironment may shed light on why only a small proportion of patients benefit from checkpoint therapy. The immune cells surrounding a tumor have been suggested to mediate an effective response to immunotherapy. However, traditional measurement of immune cell content around a tumor by immunohistochemistry, flow cytometry, or mass cytometry allows measurement of only up to a few dozen markers at a time, limiting the number of immune cell types identified. Immune cell type abundances may instead be estimatedin silicoby deconvolving gene expression mixtures from bulk RNA sequencing of tumor tissue. By measuring tens of thousands of transcripts at once, bulk RNA-seq provides a rich input to algorithms that quantify cell type abundances in the tumor microenvironment, affording the potential to quantify the states of a greater number of immune cell types (given adequate training data). Here, we first review existing methods for deconvolution and evaluate their performance on synthetic mixtures. Then we develop a Bayesian inference approach, namedinfino, that learns to distinguish immune cell expression phenotypes and deconvolve mixtures. In contrast to earlier approaches,infinoaccepts RNA sequencing data, models transcript expression variability, and exploits the relationships between cell types to improve deconvolution accuracy and allow interrogation from the level of broad categories to the level of finest granularity. The resulting probability distributions of immune infiltration could be applied to numerous questions concerning the diverse ecology of immune cell types, including assessment of the association of immune infiltration with response to immunotherapy, and study of the expression profile and presence of elusive T cell subcompartments, such as T cell exhaustion.
A multivariate analysis of CalEnviroScreen: comparing environmental and socioeconomic stressors versus chronic disease
Authors: Greenfield Ben K. , Rajan Jayant , McKone Thomas E.
Published: December 2017

Background

The health-risk assessment paradigm is shifting from single stressor evaluation towards cumulative assessments of multiple stressors. Recent efforts to develop broad-scale public health hazard datasets provide an opportunity to develop and evaluate multiple exposure hazards in combination.

Methods

We performed a multivariate study of the spatial relationship between 12 indicators of environmental hazard, 5 indicators of socioeconomic hardship, and 3 health outcomes. Indicators were obtained from CalEnviroScreen (version 3.0), a publicly available environmental justice screening tool developed by the State of California Environmental Protection Agency. The indicators were compared to the total rate of hospitalization for 14 ICD-9 disease categories (a measure of disease burden) at the zip code tabulation area population level. We performed principal component analysis to visualize and reduce the CalEnviroScreen data and spatial autoregression to evaluate associations with disease burden.

Results

CalEnviroScreen was strongly associated with the first principal component (PC) from a principal component analysis (PCA) of all 20 variables (Spearman ρ = 0.95). In a PCA of the 12 environmental variables, two PC axes explained 43% of variance, with the first axis indicating industrial activity and air pollution, and the second associated with ground-level ozone, drinking water contamination and PM2.5. Mass of pesticides used in agriculture was poorly or negatively correlated with all other environmental indicators, and with the CalEnviroScreen calculation method, suggesting a limited ability of the method to capture agricultural exposures. In a PCA of the 5 socioeconomic variables, the first PC explained 66% of variance, representing overall socioeconomic hardship. In simultaneous autoregressive models, the first environmental and socioeconomic PCs were both significantly associated with the disease burden measure, but more model variation was explained by the socioeconomic PCs.

Conclusions

This study supports the use of CalEnviroScreen for its intended purpose of screening California regions for areas with high environmental exposure and population vulnerability. Study results further suggest a hypothesis that, compared to environmental pollutant exposure, socioeconomic status has greater impact on overall burden of disease.
Active sampling state dynamically enhances olfactory bulb odor representation
Authors: Jordan Rebecca , Fukunaga Izumi , Kollo Mihaly , Schaefer Andreas T.
Published: December 2017

The olfactory bulb (OB) is the very first site of odor information processing, yet a wealth of contextual and learned information has been described in its activity. To investigate the mechanistic basis of contextual modulation, we use whole-cell recordings to measure odor responses across rapid (<30 min) learning episodes in identified mitral/tufted cells (MTCs). Across these learning episodes, we found that diverse response changes occur already during the first sniff cycle. Motivated mice develop active sniffing strategies across learning, and it is this change of active sampling state that dynamically modulates odor responses, resulting in enhanced discriminability and detectability of odor representation with learning. Evoking fast sniffing in different behavioral states demonstrates that response changes during active sampling exceed those predicted from purely feed-forward input. Finally, response changes are highly correlated in tufted cells, but not mitral cells, indicating cell-type specificity in the effect of active sampling, and resulting in increased odor detectability in the tufted and enhanced discriminability in the mitral cell population over the rapid learning episodes. Altogether, we show that active sampling state is a crucial component in modulating and enhancing olfactory bulb responsiveness on rapid timescales.
Gene expression imputation across multiple brain regions reveals schizophrenia risk throughout development
Authors: Huckins Laura M. , Dobbyn Amanda , Ruderfer Douglas M. , Hoffman Gabriel , Wang Weiqing , Pardinas Antonio , Rajagopal Veera M , Als Thomas D. , Nguyen Hoang , Girdhar Kiran , Boocock James , Roussos Panos , Fromer Menachem , Kramer Robin , Domencini Enrico , Gamazon Eric , Purcell Shaun ,   CommonMind Consortium, the Schizophrenia Working Group of the Psychiatric Genomics Consortium, iPSYCH-GEMS Schizophrenia Working Group, Ditte Demontis, Børglum Anders D. , Walters James , O’Donovan Michael , Sullivan Patrick , Owen Michael , Devlin Bernie , Sieberts Solveig K. , Cox Nancy , Im Hae Kyung , Sklar Pamela , Stahl Eli A.
Published: December 2017

Transcriptomic imputation approaches offer an opportunity to test associations between disease and gene expression in otherwise inaccessible tissues, such as brain, by combining eQTL reference panels with large-scale genotype data. These genic associations could elucidate signals in complex GWAS loci and may disentangle the role of different tissues in disease development. Here, we use the largest eQTL reference panel for the dorso-lateral pre-frontal cortex (DLPFC), collected by the CommonMind Consortium, to create a set of gene expression predictors and demonstrate their utility. We applied these predictors to 40,299 schizophrenia cases and 65,264 matched controls, constituting the largest transcriptomic imputation study of schizophrenia to date. We also computed predicted gene expression levels for 12 additional brain regions, using publicly available predictor models from GTEx. We identified 413 genic associations across 13 brain regions. Stepwise conditioning across the genes and tissues identified 71 associated genes (67 outside the MHC), with the majority of associations found in the DLPFC, and of which 14/67 genes did not fall within previously genome-wide significant loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple pathways associated with porphyric disorders. We investigated developmental expression patterns for all 67 non-MHC associated genes using BRAINSPAN, and identified groups of genes expressed specifically pre-natally or post-natally.