bluuebunny/crossref_metadata_2025 huggingface dataset:
Blue and Red Light-Evoked Pupil Responses in Photophobic Subjects with TBI
Authors: Yuhas Phillip T. , Shorter Patrick D. , McDaniel Catherine E. , Earley Michael J. , Hartwick Andrew T. E.
Published: July 2016

Purpose

Photophobia is a common symptom in individuals suffering from traumatic brain injury (TBI). Recent evidence has implicated blue light-sensitive intrinsically photosensitive retinal ganglion cells (ipRGCs) in contributing to the neural circuitry mediating photophobia in migraine sufferers. The goal of this work is to test the hypothesis that ipRGC function is altered in TBI patients with photophobia by assessing pupillary responses to blue and red light.

Methods

Twenty-four case participants (mean age 43.3; 58% female), with mild TBI and self-reported photophobia, and 12 control participants (mean age 42.6; 58% female) were in this study. After 10 minutes of dark adaptation, blue (470 nm, 1 × 1013 phots/s/cm2) and red (625 nm, 7 × 1013 phots/s/cm2) flashing (0.1 Hz) light stimuli were delivered for 30 seconds to the dilated left eye while the right pupil was recorded. The amplitude of normalized pupil fluctuation (constriction and dilation) was quantified using Fourier fast transforms.

Results

In both case and control participants, the amplitude of pupil fluctuation was significantly less for the blue light stimuli as compared to the red light stimuli, consistent with a contribution of ipRGCs to these pupil responses. There was no significant difference in the mean pupil fluctuation amplitudes between the two participant groups, but case participants displayed greater variability in their pupil responses to the blue stimulus.

Conclusions

Case and control participants showed robust ipRGC-mediated components in their pupil responses to blue light. The results did not support the hypothesis that ipRGCs are “hypersensitive” to light in TBI participants with photophobia. However, greater pupil response variability in the case subjects suggests that ipRGC function may be more heterogeneous in this group.
Objective Assessment of Vergence after Treatment of Concussion-Related CI: A Pilot Study
Authors: Scheiman Mitchell M. , Talasan Henry , Mitchell G. Lynn , Alvarez Tara L.
Published: July 2016

Purpose

To evaluate changes in objective measures of disparity vergence after office-based vision therapy (OBVT) for concussion-related convergence insufficiency (CI) and determine the feasibility of using this objective assessment as an outcome measure in a clinical trial.

Methods

This was a prospective, observational trial. All participants were treated with weekly OBVT with home reinforcement. Participants included two adolescents and three young adults with concussion-related, symptomatic CI. The primary outcome measure was average peak velocity for 4° symmetrical convergence steps. Other objective outcome measures of disparity vergence included time to peak velocity, latency, accuracy, settling time, and main sequence. We also evaluated saccadic eye movements using the same outcome measures. Changes in clinical measures (near point of convergence, positive fusional vergence at near, Convergence Insufficiency Symptom Survey [CISS] score) were evaluated.

Results

There were statistically significant and clinically meaningful changes in all clinical measures for convergence. Four of the five subjects met clinical success criteria. For the objective measures, we found a statistically significant increase in peak velocity, response accuracy to 4° symmetrical convergence and divergence step stimuli, and the main sequence ratio for convergence step stimuli. Objective saccadic eye movements (5 and 10°) appeared normal pre-OBVT and did not show any significant change after treatment.

Conclusions

This is the first report of the use of objective measures of disparity vergence as outcome measures for concussion-related convergence insufficiency. These measures provide additional information that is not accessible with clinical tests about underlying physiological mechanisms leading to changes in clinical findings and symptoms. The study results also demonstrate that patients with concussion can tolerate the visual demands (over 200 vergence and versional eye movements) during the 25-minute testing time and suggest that these measures could be used in a large-scale randomized clinical trial of concussion-related CI as outcome measures.
Vision Therapy for Binocular Dysfunction Post Brain Injury
Authors: Conrad Joseph Samuel , Mitchell G. Lynn , Kulp Marjean Taylor
Published: July 2016

Purpose

To prospectively evaluate the effectiveness of home-based computer vergence therapy for the treatment of binocular vision disorders in adults at least 3 months after an acquired brain injury.

Methods

Eligibility criteria included presence of binocular dysfunction characterized by receded near point of convergence (≥6 cm break), insufficient positive fusional vergence at near (failing Sheard’s criterion or <15△ blur or break), insufficient negative fusional vergence at near (<12△ blur or break), and/or reduced vergence facility at near (<15 cycles per minute with 12△BO/3△BI). Participants were prescribed 12 weeks of home-based computer vergence therapy. Phoria (cover test), negative fusional vergence, positive fusional vergence, near point of convergence, vergence facility, and symptoms (convergence insufficiency symptom survey [CISS]) were assessed at baseline and after 4, 8, and 12 weeks of prescribed therapy. ANOVA was used to evaluate change in each measure. Percentage successful was also determined.

Results

Nineteen participants were enrolled (mean age 45.4 ± 12.9 years); six participants were lost to follow-up. Baseline findings were orthophoria at distance, 7.2△ exophoria at near, near point of convergence break = 17.5 cm, near point of convergence recovery = 21.8 cm, negative fusional vergence = 12.3△, positive fusional vergence blur = 8.4△, vergence facility = 3.9 cycles per minute, and CISS = 32.1. ANOVA showed a statistically significant improvement for near point of convergence break (p = 0.002) and recovery (p < 0.001), positive fusional vergence blur (p < 0.0001), break (p < 0.0001), and recovery (p < 0.0001), negative fusional vergence blur (p = 0.037), break (p = 0.003), and recovery (p = 0.006), vergence facility (p < 0.0001), and CISS (p = 0.0001). The percentage of patients who were classified as “successful” or “improved” was 69% for near point of convergence (<6 cm or decrease of ≥4 cm), 77% for positive fusional vergence (>15△ and passing Sheard’s criterion or increase of ≥10△), 77% for negative fusional vergence (≥12△ or increase of ≥6△), 62% for positive fusional vergence and near point of convergence composite, and 92% for vergence facility (15 cycles per minute or increase of 3 cycles per minute).

Conclusions

The majority of participants who completed the study experienced meaningful improvements in signs and symptoms.
Programmed Death-Ligand 1 Expression Is Common in Gastric Cancer Associated With Epstein-Barr Virus or Microsatellite Instability
Authors: Ma Changqing , Patel Krishna , Singhi Aatur D. , Ren Bing , Zhu Benjamin , Shaikh Fyza , Sun Weijing
Published: July 2016

Blockade of the programmed death 1 (PD-1) pathway has emerged as a novel therapy for cancer. Therefore, development of biomarkers for response prediction, such as PD-ligand 1 (PD-L1) expression by immunohistochemistry, may help to stratify patients. Solid tumors with CD8 T-cell rich tumor microenvironment have been implicated to be associated with increased PD-L1 expression. We hypothesized that gastric cancers associated with Epstein-Barr virus infection (EBV+) or microsatellite instability (MSI), both of which are known to harbor such tumor microenvironment, are associated with increased PD-L1 expression. Forty-four resected gastric cancers including 7 EBV+, 16 MSI, and 21 microsatellite stable cancers without EBV (EBV−/MSS) were studied for PD-L1 expression and T-cell subpopulations by immunohistochemistry. Positive PD-L1 expression (PD-L1+), defined as membranous staining in either tumor cells or tumor immune infiltrates, was seen in 32 (72%) gastric cancers. EBV+ or MSI cancers showed significantly higher rates of PD-L1+ compared with EBV−/MSS cancers (7/7, 100%; 14/16, 87%; 11/21, 52%; P=0.013). PD-L1+/EBV+ and PD-L1+/MSI cancers had significantly more CD8 T cells at tumor invasive front than PD-L1+/EBV−/MSS cancers (P<0.001). PD-L1+ was not associated with the depth of invasion or nodal metastasis (P=0.534, 0.288). Multivariate analysis showed PD-L1+ was not an independent predictor of disease-free survival while MSI was (P=0.548, 0.043). In summary, EBV+ or MSI gastric cancers are more likely to express PD-L1 and have increased CD8 T cells at tumor invasive front than EBV−/MSS cancers. Our results suggest EBV infection and MSI should be investigated for predicting response to PD-1 blockade.
Survey of Sedation and Analgesia Practice Among Canadian Pediatric Critical Care Physicians*
Authors: Garcia Guerra Gonzalo , Joffe Ari R. , Cave Dominic , Duff Jonathan , Duncan Shannon , Sheppard Cathy , Tawfik Gerda , Hartling Lisa , Jou Hsing , Vohra Sunita
Published: July 2016

Background:

Despite the fact that almost all critically ill children experience some degree of pain or anxiety, there is a lack of high-quality evidence to inform preferred approaches to sedation, analgesia, and comfort measures in this environment. We conducted this survey to better understand current comfort and sedation practices among Canadian pediatric intensivists.

Methods:

The survey was conducted after a literature review and initial focus groups. The survey was then pretested and validated. The final survey was distributed by email to 134 intensivists from 17 PICUs across Canada using the Research Electronic Data Capture system.

Results:

The response rate was 73% (98/134). The most commonly used sedation scores are Face, Legs, Activity, Cry, and Consolability (42%) and COMFORT (41%). Withdrawal scores are commonly used (65%). In contrast, delirium scores are used by only 16% of the respondents. Only 36% of respondents have routinely used sedation protocols. The majority (66%) do not use noise reduction methods, whereas only 23% of respondents have a protocol to promote day/night cycles. Comfort measures including music, swaddling, soother, television, and sucrose solutions are frequently used. The drugs most commonly used to provide analgesia are morphine and acetaminophen. Midazolam and chloral hydrate were the most frequent sedatives.

Conclusion:

Our survey demonstrates great variation in practice in the management of pain and anxiety in Canadian PICUs. Standardized strategies for sedation, delirium and withdrawal, and sleep promotion are lacking. There is a need for research in this field and the development of evidence-based, pediatric sedation and analgesia guidelines.
The Influence of Different Solvents on Systemic Sclerosis
Authors: Zhao Jiu-Hua , Duan Yu , Wang Yu-Jie , Huang Xiao-Lei , Yang Guo-Jun , Wang Jing
Published: July 2016

Background

Several studies have collected detailed data to examine which specific solvents account for the association between solvents and risk of systemic sclerosis (SSc). These studies generally reported elevated risks associated with many of the specific solvents examined, such as toluene, xylene, and trichloroethylene. The previous meta-analysis was not able to conduct separate analyses for specific solvent subtypes.

Objective

The aims of the new meta-analysis were to investigate a more comprehensive estimate and to consider the effect of different solvents on SSc.

Methods

We searched PubMed, Biosis Previews, China National Knowledge Infrastructure, and Wanfang for all articles published before July 2015. Fourteen case-control studies (1657 patients and 3838 controls) were included. The quality of studies was scored according to the Newcastle-Ottawa scale. The final odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed- or random-effects model according to heterogeneity test. Publication bias was assessed using Begg test.

Results

The risk of SSc was significantly different among sex, age, and exposure assessment methods. Separate analyses for specific solvent subtypes indicated that SSc was associated with aromatic solvents (OR, 2.72; 95% CI, 1.21–6.09), trichloroethylene (OR, 2.07; 95% CI, 1.34–3.17), halogenated solvents (OR, 1.49; 95% CI, 1.12–1.99), and ketones (OR, 4.20; 95% CI, 2.19–8.06).

Conclusions

Exposure to identified types solvents does seem to be a risk factor for developing SSc. Needed efforts to decrease such exposures are discussed.
Sleep Quality Is Related to Disease Activity in Patients With Ankylosing Spondylitis
Authors: İn Erdal , Turgut Teyfik , Gülkesen Arif , Yolbaş Servet , Akgöl Gürkan , Koca Süleyman Serdar
Published: July 2016

Background

Ankylosing spondylitis (AS) is a chronic inflammatory disease that is associated with poor sleep quality.

Objectives

The present study aimed to investigate the relationship between disease activity and sleep quality in patients with AS and to evaluate the potential effect of anti–tumor necrosis factor (TNF) treatment on sleep quality and pattern.

Methods

Fifty-nine patients with AS were consecutively included in the study. Twenty-eight patients (47.5%) were receiving anti-TNF, and 31 (52.5%) patients were receiving only nonsteroidal anti-inflammatory drugs (NSAIDs). Demographic and treatment characteristics, spinal mobility measurements, disease activity measurements, and sleep questionnaire results of each patient were recorded. Each patient underwent a polysomnography examination for the evaluation of sleep patterns.

Results

When compared with the patients on NSAID treatment, patients receiving anti-TNF treatment had significantly greater total sleep time and sleep efficiency (P = 0.003 and P < 0.001, respectively). They had a significantly lower (better) Pittsburgh Sleep Quality Index, sleep onset latency, number of awakenings, and arousal index (P < 0.001, for all). Moreover, they had a significantly shorter superficial sleep period (stage 1) and a significantly longer rapid eye movement sleep period (P < 0.001 and P = 0.02, respectively). Higher indexes of disease activity (Bath AS Disease Activity Index, Bath AS Functional Index, and visual analog scale) were reflecting poorer sleep quality.

Conclusions

Sleep quality and pattern was markedly better in patients with AS on anti-TNF compared with the patients on NSAID treatments. Increased disease activity can impair the quality of sleep in AS. Improved sleep quality and pattern in patients on anti-TNF treatment may be related to improved disease activity.
Leprosy Masquerading as Systemic Rheumatic Diseases
Authors: El-Gendy Hala , El-Gohary Rasmia M. , Shohdy Kyrillus S. , Ragab Gaafar
Published: July 2016

Rheumatologic manifestations not only are encountered in leprosy but also can be the first and even the sole presenting manifestation. The hallmark of leprosy is skin and peripheral nerve affection; however, it can affect a wide range of other organs, with the joints being the commonest. We have searched PubMed with the key words leprosy, arthritis, vasculitis, rheumatic diseases, and autoantibodies in a proper combination. Relevant studies were retrieved from scanning of their abstracts. The relevant references provided in these articles were also selected and reviewed. We summarize the clinical and laboratory manifestations that make leprosy masquerade as a systemic rheumatic disease. Moreover, we report 4 Egyptian patients who presented with rheumatologic manifestations, namely, arthritis and vasculitis that turned out to be leprosy related.
Rheumatology Resources in a Region of Buenos Aires Province, Argentina
Authors: Fara Nauan , Sequeira Gabriel
Published: July 2016

Background

Accurate knowledge of the available rheumatology workforce and their working conditions results in better care for patients with rheumatic diseases.

Objective

The aim of this study was to assess the rheumatology resources and their distribution within district V of the College of Physicians (COLMED5) of Buenos Aires Province, Argentina.

Methods

All the registered rheumatologists and all the registered public and private institutions within COLMED5 were identified. Aside from these data, phone calls, letters, Internet-derived information, and databases from public and private health insurance providers and the Argentine Society of Rheumatology were included as well. Rheumatologists’ per-capita rates were built for both the whole district and every town. A rate of at least 1 rheumatologist per 50,000 people was deemed an optimal resource.

Results

Thirty-six rheumatologists were identified; the calculated rate was 1 rheumatologist per 68,403 people; 44% of the health care institutions had a rheumatologist; 33% of them were public institutions. Only 25.5% of COLMED5 total population had optimal rheumatology resources in their town, 70.3% did not reach the optimal resource level but at least had a rheumatologist in their town, and 4.2% had no resources whatsoever; 49% of the total population lacked public health care facilities with inpatient settings and rheumatologists in their town.

Conclusions

Although COLMED5 has 72% of the optimal number of rheumatologists, because of their uneven distribution, only 25.5% of the district’s total population has the optimal rheumatology resources in their town. Nearly half COLMED5 total population lacks public health care facilities with inpatient settings and rheumatologists in their town, and 4.2% has no available rheumatology resource at all.
Treatment of Large Thyroglossal Duct Cyst
Authors: Bezerra Júnior Germano de Lelis , Silva Leonardo de Freitas , Pimentel Gabriel Gomes , Laureano Filho José Rodrigues , Nogueira Renato Luiz Maia
Published: July 2016

The thyroglossal duct cyst is the neck congenital abnormality most common in the childhood. Clinically, it shows itself as a solitary neck mass in the region of hyoid bone, it is painless and can be dislocated during de physical examination and tongue protrusion. The most common treatment is its removal through the Sistrunk technique. Patient with diagnosis of thyroglossal duct cyst in neck region with extension to the mouth floor was treated by total surgical removal through intraoral access. The intraoral approach to the treatment of the thyroglossal duct cyst showed itself practicable and permitted the total removal of the lesion with no recurrence signs.
Risk Factors for Cholelithiasis
Authors: Pak Mila , Lindseth Glenda
Published: July 2016

Gallstone disease is one of the most common public health problems in the United States. Approximately 10%–20% of the national adult populations currently carry gallstones, and gallstone prevalence is rising. In addition, nearly 750,000 cholecystectomies are performed annually in the United States; direct and indirect costs of gallbladder surgery are estimated to be $6.5 billion. Cholelithiasis is also strongly associated with gallbladder, pancreatic, and colorectal cancer occurrence. Moreover, the National Institutes of Health estimates that almost 3,000 deaths (0.12% of all deaths) per year are attributed to complications of cholelithiasis and gallbladder disease. Although extensive research has tried to identify risk factors for cholelithiasis, several studies indicate that definitive findings still remain elusive. In this review, predisposing factors for cholelithiasis are identified, the pathophysiology of gallstone disease is described, and nonsurgical preventive options are discussed. Understanding the risk factors for cholelithiasis may not only be useful in assisting nurses to provide resources and education for patients who are diagnosed with gallstones, but also in developing novel preventive measures for the disease.
Sexual Function After Stroke
Authors: Thomas Heather
Published: July 2016

This article describes the case of a 69-year-old, married, Hispanic heterosexual woman who suffered a right cerebral vascular accident. Assessment measures utilized to identify barriers to sexual activity were the Canadian Occupational Performance Measure, Quality of Sexual Function Scale, and the Stroke Impact Scale. Goals were established in collaboration with the client, and interventions addressed a wide range of barriers. This case demonstrates how occupational therapy and the interprofessional team addressed limitations in engagement in sexual activities. Data collected postintervention showed significant changes in sexual activity, satisfaction, and perceived quality of life. This case demonstrates the importance of addressing sexual activity with clients poststroke and how the health care team can implement strategies to help clients address barriers to this essential human activity.
Sexual Function and the Cancer Patient
Authors: Westermann Melissa , Wolford Juliet , Krychman Michael
Published: July 2016

Sexual health is paramount to the well-being of the geriatric gynecologic oncology cancer survivor and yet often overlooked by providers. Sexual dysfunction in this population originates from baseline normal aging, with concomitant exacerbation from the physical, psychological, and behavioral effects of cancer treatments. Rehabilitation is manifested in a multitude of therapies, including psychological evaluations, physical therapy, behavioral modifications, medical therapies, and sexual pharmacology. Provider and patient recognition of sexual dysfunction can aid in the exploration of treatments to help expedite improvement in quality of life and sexuality, establishing recovery toward a new normal.
Psychosocial Aspects of Sexuality With Aging
Authors: Brandon Marianne
Published: July 2016

Sexual intimacy may be the most private aspect of life, a topic commonly avoided between sex partners or even between a patient and his or her medical professional. Most of the time, sex is an interpersonal experience, occurring within a couple. The physical, emotional, and relationship challenges that often accompany the aging process may add complexity to one's sexual experience and expression. This article explores some potential interpersonal variables that can impact sexual satisfaction and function with age. As the numbers of seniors continue to rise, health practitioners will be increasingly called upon to assist these patients with their sexual concerns.
The Role of Perilipins in the Development of Obesity and Obesity-Related Diseases
Authors: Nicolaidou Katerina , Isoldi Kathy K. , Ramer Nicholas J. , Sarcona Alessandra
Published: July 2016

Understanding nonmodifiable factors promoting weight gain can help clinicians reduce their bias and improve patient care. This review outlines research linking perilipins with the regulation of body fat. Perilipins are proteins that coat lipid droplets. There are 5 known perilipins with varying functions, and perilipin 1 is the most widely researched of all. Rodent studies found a strong link between perilipin 1 and increased fat mass; however, studies with human subjects found inconsistencies, perhaps because of sex and genetic variations. Although some inconsistencies are evident, an association between perilipins and the development of obesity has been established.
Classification of Kidney Transplant Recipients Using a Combination of Estimated GFR and Albuminuria Reflects Risk
Authors: White Christine A. , Akbari Ayub , Talreja Hari , Lalani Neha , Knoll Greg A.
Published: July 2016

Background

The 2012 Kidney Dialysis Initiative Global Outcomes chronic kidney disease (CKD) classification scheme subdivides stage 3 CKD and incorporates the urinary albumin-to-creatinine ratio (ACR). The aim of this study was to evaluate whether the novel scheme provides graded risk in kidney transplant recipients (KTRs).

Methods

Prevalent KTRs with available laboratory data were included. The primary outcome was a composite of doubling of serum creatinine, graft failure, or death. Patients were stratified using the CKD-Epidemiolgic Collaboration equation, and ACR and the event rate per 1000 patient-years in each CKD category were calculated.

Results

There were 269 KTRs with a mean follow-up of 4.5 ± 2.0 years. There was a graded increase in outcomes with increasing ACR and decreasing estimated glomerular filtration rate (eGFR). For the primary outcome, the event rate was 15.3 (95% confidence interval, 4.2-39.2) per 1000 patient-years for those with an eGFR greater than 60 mL/min per 1.73 m2 and an ACR less than 30 mg/g, whereas it was 375 (95% confidence interval, 193.8-655.1) for those with an eGFR less than 30 mL/min per 1.73 m2 and an ACR greater than 300 mg/g.

Conclusions

The novel Kidney Dialysis Initiative Global Outcomes classification scheme provides graded risk for important clinical events in KTRs. This information can be used to identify high-risk patients and to tailor follow-up and management strategies aimed at improving outcomes.
MRI Markers Predict Cognitive Decline Assessed by Telephone Interview
Authors: Wright Clinton B. , Dong Chuanhui , Caunca Michelle R. , DeRosa Janet , Kuen Cheng Ying , Rundek Tatjana , Elkind Mitchell S.V. , DeCarli Charles , Sacco Ralph L.
Published: July 2016

Background:

Brain magnetic resonance imaging (MRI) allows researchers to observe structural pathology that may predict cognitive decline. Some populations are less accessible through traditional in-person visits, and may be under-represented in the literature.

Methods:

We examined white matter hyperintensity volume (WMHV) and cerebral parenchymal fraction (CPF) as predictors of cognitive decline measured by a modified Telephone Interview for Cognitive Status (TICS-m) in the Northern Manhattan Stroke Study, a racially and ethnically diverse cohort study. Participants were stroke-free, above 50 years old, and had no contraindications to MRI. A total of 1143 participants had MRI and TICS-m data available [mean age 70 (SD=9), 61% women, 66% Hispanic, 17% Black, 15% white].

Results:

Those in the third and fourth quartiles of WMHV had significantly greater decline in TICS-m over time as compared with those in the first quartile (Q3: −0.17 points/year, Q4: −0.30 points/year). Those in the bottom 2 quartiles of CPF had significantly greater decline in TICS-m than those in the top quartile (Q1: −0.3 points/year, Q2: −0.2 points/year). Apolipoprotein E (APOE) e4 allele carriers had greater cognitive decline per unit of CPF. Those with greater CPF preserve TICS-m performance better despite greater WMHV.

Conclusions:

Telephone cognitive assessments can detect decline due to white matter lesions and smaller brain volumes.
Optic Disc Metastasis as the Presenting Sign of Lung Adenocarcinoma
Authors: Micieli Jonathan A. , Margolin Edward A.
Published: July 2016

A 67-year-old woman noticed vision loss in her right eye and was found to have an elevated, well-circumscribed white mass within the right optic disc. The patient underwent an evaluation which revealed 4 brain metastases and a large left hilar mass that proved to be adenocarcinoma of the lung. Because she continued to lose vision, the optic disc metastasis was treated with stereotactic radiotherapy. Although she reported vision improvement, she died soon afterward. There are 9 previous reports in the English literature of isolated optic disc metastasis as the presenting sign of cancer. Familiarity with the features of optic disc metastasis can lead to earlier recognition and treatment of the underlying malignant neoplasm.
Does allopreening control avian ectoparasites?
Authors: Villa Scott M. , Goodman Graham B. , Ruff James S. , Clayton Dale H.
Published: July 2016

For birds, the first line of defence against ectoparasites is preening. The effectiveness of self-preening for ectoparasite control is well known. By contrast, the ectoparasite control function of allopreening—in which one birds preens another—has not been rigorously tested. We infested captive pigeons with identical numbers of parasitic lice, and then compared rates of allopreening to the abundance of lice on the birds over time. We documented a negative relationship between rates of allopreening and the number of lice on birds. Moreover, we found that allopreening was a better predictor of louse abundance than self-preening. Our data suggest that allopreening may be a more important means of ectoparasite defence than self-preening when birds live in groups. Our results have important implications for the evolution of social behaviour.
Brian Eyre CBE FREng. 29 November 1933 — 28 July 2014
Authors: Pooley Derek , Smith George , Windsor Colin
Published: July 2016

Brian Eyre was an outstanding metallurgist who played a leading role in the development of nuclear engineering materials. His experiments on irradiated metals enabled a theoretical understanding of the mechanisms of radiation damage, and in particular the formation of voids and void swelling in structural steels. His work on the fracture of metals advanced our understanding of intergranular embrittlement and helped define the specifications of the structural components in nuclear reactors. He rose from a humble upbringing in London's East End to become Chief Executive of the UK Atomic Energy Authority (UKAEA). He was instrumental in transforming the UKAEA from a organization whose mission was to develop nuclear power generating systems into the privatized AEA Technology, which worked on a wide range of technologies on a customer–contractor basis.
Neonicotinoid insecticides can serve as inadvertent insect contraceptives
Authors: Straub Lars , Villamar-Bouza Laura , Bruckner Selina , Chantawannakul Panuwan , Gauthier Laurent , Khongphinitbunjong Kitiphong , Retschnig Gina , Troxler Aline , Vidondo Beatriz , Neumann Peter , Williams Geoffrey R.
Published: July 2016

There is clear evidence for sublethal effects of neonicotinoid insecticides on non-target ecosystem service-providing insects. However, their possible impact on male insect reproduction is currently unknown, despite the key role of sex. Here, we show that two neonicotinoids (4.5 ppb thiamethoxam and 1.5 ppb clothianidin) significantly reduce the reproductive capacity of male honeybees (drones),
Apis mellifera
. Drones were obtained from colonies exposed to the neonicotinoid insecticides or controls, and subsequently maintained in laboratory cages until they reached sexual maturity. While no significant effects were observed for male teneral (newly emerged adult) body mass and sperm quantity, the data clearly showed reduced drone lifespan, as well as reduced sperm viability (percentage living versus dead) and living sperm quantity by 39%. Our results demonstrate for the first time that neonicotinoid insecticides can negatively affect male insect reproductive capacity, and provide a possible mechanistic explanation for managed honeybee queen failure and wild insect pollinator decline. The widespread prophylactic use of neonicotinoids may have previously overlooked inadvertent contraceptive effects on non-target insects, thereby limiting conservation efforts.
Divergent evolution peaks under intermediate population bottlenecks during bacterial experimental evolution
Authors: Vogwill Tom , Phillips Robyn L. , Gifford Danna R. , MacLean R. Craig
Published: July 2016

There is growing evidence that parallel molecular evolution is common, but its causes remain poorly understood. Demographic parameters such as population bottlenecks are predicted to be major determinants of parallelism. Here, we test the hypothesis that bottleneck intensity shapes parallel evolution by elucidating the genomic basis of adaptation to antibiotic-supplemented media in hundreds of populations of the bacteriumPseudomonas fluorescensPf0-1. As expected, bottlenecking decreased the rate of phenotypic and molecular adaptation. Surprisingly, bottlenecking had no impact on the likelihood of parallel adaptive molecular evolution at a genome-wide scale. However, bottlenecking had a profound impact on the genes involved in antibiotic resistance. Specifically, under either intense or weak bottlenecking, resistance predominantly evolved by strongly beneficial mutations which provide high levels of antibiotic resistance. In contrast with intermediate bottlenecking regimes, resistance evolved by a greater diversity of genetic mechanisms, significantly reducing the observed levels of parallel genetic evolution. Our results demonstrate that population bottlenecking can be a major predictor of parallel evolution, but precisely how may be more complex than many simple theoretical predictions.
Ocean acidification affects fish spawning but not paternity at CO
2
seeps
Authors: Milazzo Marco , Cattano Carlo , Alonzo Suzanne H. , Foggo Andrew , Gristina Michele , Rodolfo-Metalpa Riccardo , Sinopoli Mauro , Spatafora Davide , Stiver Kelly A. , Hall-Spencer Jason M.
Published: July 2016

Fish exhibit impaired sensory function and altered behaviour at levels of ocean acidification expected to occur owing to anthropogenic carbon dioxide emissions during this century. We provide the first evidence of the effects of ocean acidification on reproductive behaviour of fish in the wild. Satellite and sneaker male ocellated wrasse (
Symphodus ocellatus
) compete to fertilize eggs guarded by dominant nesting males. Key mating behaviours such as dominant male courtship and nest defence did not differ between sites with ambient versus elevated CO
2
concentrations. Dominant males did, however, experience significantly lower rates of pair spawning at elevated CO
2
levels. Despite the higher risk of sperm competition found at elevated CO
2
, we also found a trend of lower satellite and sneaker male paternity at elevated CO
2
. Given the importance of fish for food security and ecosystem stability, this study highlights the need for targeted research into the effects of rising CO
2
levels on patterns of reproduction in wild fish.
Biophysical properties of human β-cardiac myosin with converter mutations that cause hypertrophic cardiomyopathy
Authors: Kawana Masataka , Sarkar Saswata S , Sutton Shirley , Ruppel Kathleen M , Spudich James
Published: July 2016

Hypertrophic cardiomyopathy (HCM) affects 1 in 500 individuals and is an important cause of arrhythmias and heart failure. Clinically, HCM is characterized as causing hyper-contractility, and therapies are aimed toward controlling the hyperactive physiology. β-cardiac myosin comprises ~40 percent of genetic mutations associated with HCM and the converter domain of myosin is a hot spot for HCM-causing mutations, but the underlying primary effects of these mutations on myosin's biomechanical function remain elusive. We hypothesize that these mutations affect the biomechanical properties of myosin, such as increasing its intrinsic force and/or its duty ratio and therefore the ensemble force of the sarcomere. Using recombinant human β-cardiac myosin, we characterize the molecular effects of three severe HCM-causing converter domain mutations R719W, R723G and G741R. Contrary to our hypothesis, the intrinsic forces of R719W and R723G mutant myosins are decreased compared to wild type, and unchanged for G741R. Actin and regulated thin filament gliding velocities are ~15 percent faster for R719W and R723G myosin, while there is no change in velocity for G741R. ATPase activities and the load-dependent velocity change profiles of all three mutant proteins are very similar to wild type. These results indicate that the net biomechanical properties of human β-cardiac myosin carrying these converter domain mutations are very similar to wild type or even slightly hypo-contractile, leading us to consider an alternative mechanism for the clinically observed hyper-contractility. Future work includes how these mutations affect protein interactions within the sarcomere that increase the availability of myosin heads participating in force production.
Discovery of Cancer Driver Long Noncoding RNAs across 1112 Tumour Genomes: New Candidates and Distinguishing Features
Authors: Lanzós Andrés , Carlevaro-Fita Joana , Mularoni Loris , Reverter Ferran , Palumbo Emilio , Guigó Roderic , Johnson Rory
Published: July 2016

Long noncoding RNAs (lncRNAs) represent a vast unexplored genetic space that may hold missing drivers of tumourigenesis, but few such “driver lncRNAs” are known. Until now, they have been discovered through changes in expression, leading to problems in distinguishing between causative roles and passenger effects. We here present a different approach for driver lncRNA discovery using mutational patterns in tumour DNA. Our pipeline, ExInAtor, identifies genes with excess load of somatic single nucleotide variants (SNVs) across panels of tumour genomes. Heterogeneity in mutational signatures between cancer types and individuals is accounted for using a simple local trinucleotide background model, which yields high precision and low computational demands. We use ExInAtor to predict drivers from the GENCODE annotation across 1112 entire genomes from 23 cancer types. Using a stratified approach, we identify 15 high-confidence candidates: 9 novel and 6 known cancer-related genes, includingMALAT1,NEAT1andSAMMSON. Both known and novel driver lncRNAs are distinguished by elevated gene length, evolutionary conservation and expression. We have presented a first catalogue of mutated lncRNA genes driving cancer, which will grow and improve with the application of ExInAtor to future tumour genome projects.
Chaotic propagation of spatial cytoskeletal instability modulates integrity of podocyte foot processes
Authors: Falkenberg Cibele V. , Azeloglu Evren U. , Stothers Mark , Deerinck Thomas J. , Chen Yibang , He John C. , Ellisman Mark H. , Hone James C. , Iyengar Ravi , Loew Leslie M.
Published: July 2016

The kidney podocyte’s function depends on its distinctive morphology. Each podocyte has fingerlike projections, called foot processes, that interdigitate with the processes of neighboring cells to form the glomerular filtration barrier. The integrity of foot process interactions depends on tight spatial control of the dynamics of the underlying actin cytoskeleton, which is regulated by the GTPases, Rac1 and RhoA. To understand how spatially-specific regulation of actin filament dynamics within foot processes controls local morphology, we used a combination of 3-D microscopy and dynamical models. We experimentally determined cell-cell interactions using serial blockface scanning electron microscopy and reconstructed a 3-D spatial representation of a podocyte. We developed a minimal dynamical system for regulation of the actin cytoskeleton; using this 3-D model, we determined how spatial reaction-diffusion dynamics can dysregulate actin bundling, leading to propagation of chaotic foot process effacement. Consistent with experimental observations, our simulations predicted that hyperactive RhoA could destabilize the cytoskeleton. Our simulations showed that deleterious mechanochemical stimuli could lead to local heterogeneity of cytoskeletal dynamics resulting in the emergence of progressive and chaotic loss of foot processes. While global enhancement of Rac1 may result in stronger bundles, the spatial simulations showed that even transient local heterogeneities in polymerization could have dramatic consequences in the stability of multiple foot processes. We conclude that the podocyte morphology optimized for filtration contains intrinsic fragility whereby local imbalances in biochemical and biophysical reactions lead to morphological changes associated with glomerular pathophysiology.
AFNI and Clustering: False Positive Rates Redux
Authors: Cox Robert W , Reynolds Richard C , Taylor Paul A
Published: July 2016

In response to reports of inflated false positive rate (FPR) in FMRI group analysis tools, a series of replications, investigations, and software modifications were made to address this issue. While these investigations continue, significant progress has been made to adapt AFNI to fix such problems. Two separate lines of changes have been made. First, a long-tailed model for the spatial correlation of the FMRI noise characterized by autocorrelation function (ACF) was developed and implemented into the 3dClustSim tool for determining the cluster-size threshold to use for a given voxel-wise threshold. Second, the 3dttest++ program was modified to do randomization of the voxel-wise t-tests and then to feed those randomizedt-statistic maps into 3dClustSim directly for cluster-size threshold determination-without any spatial model for the ACF. These approaches were tested with the Beijing subset of the FCON-1000 data collection. The first approach shows markedly improved (reduced) FPR, but in many cases is still above the nominal 5%. The second approach shows FPRs clustered tightly about 5% across all per-voxelp-value thresholds ≤ 0.01. Ift-tests from a univariate GLM are adequate for the group analysis in question, the second approach is what the AFNI group currently recommends for thresholding. If more complex per-voxel statistical analyses are required (where permutation/randomization is impracticable), then our current recommendation is to use the new ACF modeling approach coupled with a per-voxelp-threshold of 0.001 or below. Simulations were also repeated with the now infamously “buggy” version of 3dClustSim: the effect of the bug on FPRs was minimal (of order a few percent).
Massively parallel digital transcriptional profiling of single cells
Authors: Zheng Grace X.Y. , Terry Jessica M. , Belgrader Phillip , Ryvkin Paul , Bent Zachary W. , Wilson Ryan , Ziraldo Solongo B. , Wheeler Tobias D. , McDermott Geoff P. , Zhu Junjie , Gregory Mark T. , Shuga Joe , Montesclaros Luz , Masquelier Donald A. , Nishimura Stefanie Y. , Schnall-Levin Michael , Wyatt Paul W , Hindson Christopher M. , Bharadwaj Rajiv , Wong Alexander , Ness Kevin D. , Beppu Lan W. , Deeg H. Joachim , McFarland Christopher , Loeb Keith R. , Valente William J. , Ericson Nolan G. , Stevens Emily A. , Radich Jerald P. , Mikkelsen Tarjei S. , Hindson Benjamin J. , Bielas Jason H.
Published: July 2016

Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3′ mRNA counting of up to tens of thousands of single cells per sample. Cell encapsulation in droplets takes place in ∼6 minutes, with ∼50% cell capture efficiency, up to 8 samples at a time. The speed and efficiency allow the processing of precious samples while minimizing stress to cells. To demonstrate the system′s technical performance and its applications, we collected transcriptome data from ∼¼ million single cells across 29 samples. First, we validate the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs. Then, we profile 68k peripheral blood mononuclear cells (PBMCs) to demonstrate the system′s ability to characterize large immune populations. Finally, we use sequence variation in the transcriptome data to determine host and donor chimerism at single cell resolution in bone marrow mononuclear cells (BMMCs) of transplant patients. This analysis enables characterization of the complex interplay between donor and host cells and monitoring of treatment response. This high-throughput system is robust and enables characterization of diverse biological systems with single cell mRNA analysis.
A Novel Family of Genomics Islands Across Multiple Species ofStreptococcus
Authors: Wang Jing , Wang Changjun , Feng Weizhong , Feng Youjun , Zhi Liming , Li Wenjuan , Yao Yi , Jiang Shibo , Tang Jiaqi
Published: July 2016

The genusStreptococcusis one of the most genomically diverse and important human and agricultural pathogens. The acquisition of genomic islands (GIs) plays a central role in adaptation to new hosts in the genus pathogens. The research presented here employs a comparative genomics approach to define a novel family of GIs in the genusStreptococcuswhich also appears across strains of the same species. Specifically, we identified 9Streptococcusgenomes out of 67 sequenced genomes analyzed, and we termed these as 15bpStreptococcusgenomic islands, or 15SGIs, including i) insertion adjacent to the 3’ end of ribosomel7/l12gene, ii) large inserts of horizontally acquired DNA, and iii) the presence of mobility genes (integrase) and replication initiators. We have identified a novel family of 15SGIs and seems to be important in species differentiation and adaptation to new hosts. It plays an important role during strain evolution in the genusStreptococcus.
The role of brain oscillations in predicting the sensory consequences of your actions
Authors: Cao Liyu , Thut Gregor , Gross Joachim
Published: July 2016

Being able to predict self-generated sensory consequences is an important feature of normal brain functioning. In the auditory domain, self-generated sounds lead to smaller brain responses compared to externally generated sounds. Here we investigated the role of brain oscillations underlying this effect. With magnetoencephalography, we show that self-generated sounds are associated with increased pre-stimulus alpha power and decreased post-stimulus gamma power and alpha/beta phase locking in auditory cortex. All these oscillatory changes are correlated with changes in evoked responses. Furthermore, they correlate with each other across participants, supporting the idea that they constitute a neural information processing sequence for self-generated sounds, with pre-stimulus alpha power representing prediction and post-stimulus gamma power representing prediction error, which is further processed with post-stimulus alpha/beta phase resetting. Additional cross-trial analysis provides further support for the proposed sequence that might reflect a general mechanism for the prediction of self-generated sensory input.
Phosphoproteomics-based Profiling of Kinase Activities in Cancer Cells
Authors: Wirbel Jakob , Cutillas Pedro , Saez-Rodriguez Julio
Published: July 2016

Cellular signaling, predominantly mediated by phosphorylation through protein kinases, is found to be deregulated in most cancers. Accordingly, protein kinases have been subject to intense investigations in cancer research, to understand their role in oncogenesis and to discover new therapeutic targets. Despite great advances, an understanding of kinase dysfunctioning in cancer is far from complete.

A powerful tool to investigate phosphorylation is mass-spectrometry (MS)-based phosphoproteomics, which enables the identification of thousands of phosphorylated peptides in a single experiment. Since every phosphorylation event results from the activity of a protein kinase, high-coverage phosphoproteomics data should indirectly contain comprehensive information about the activity of protein kinases.

In this chapter, we discuss the use of computational methods to predict kinase activity scores from MS-based phosphoproteomics data. We start with a short explanation of the fundamental features of the phosphoproteomics data acquisition process from the perspective of the computational analysis. Next, we briefly review the existing databases with experimentally verified kinase-substrate relationships and present a set of bioinformatic tools to discover novel kinase targets. We then introduce different methods to infer kinase activities from phosphoproteomics data and these kinase-substrate relationships. We illustrate their application with a detailed protocol of one of the methods, KSEA (Kinase Substrate Enrichment Analysis). This method is implemented in Python within the framework of the open-source Kinase Activity Toolbox (kinact), which is freely available athttp://github.com/saezlab/kinact/.