bluuebunny/crossref_metadata_2025 huggingface dataset:
Progression of Unilateral Hearing Loss in Children With and Without Ipsilateral Cochlear Nerve Canal Stenosis: A Hazard Analysis
Authors: Purcell Patricia L. , Shinn Justin R. , Coggeshall Scott S. , Phillips Grace , Paladin Angelisa , Sie Kathleen C. Y. , Horn David L.
Published: May 2017

Objective:

To investigate the risk of hearing loss progression in each ear among children with unilateral hearing loss associated with ipsilateral bony cochlear nerve canal (BCNC) stenosis.

Setting:

Tertiary pediatric referral center.

Patients:

Children diagnosed with unilateral hearing loss who had undergone temporal bone computed tomography imaging and had at least 6 months of follow-up audiometric testing were identified from a prospective audiological database.

Interventions:

Two pediatric radiologists blinded to affected ear evaluated imaging for temporal bone anomalies and measured bony cochlear canal width independently. All available audiograms were reviewed, and air conduction thresholds were documented.

Main Outcome Measure:

Progression of hearing loss was defined by a 10 dB increase in air conduction pure-tone average.

Results:

One hundred twenty eight children met inclusion criteria. Of these, 54 (42%) had a temporal bone anomaly, and 22 (17%) had ipsilateral BCNC stenosis. At 12 months, rates of progression in the ipsilateral ear were as follows: 12% among those without a temporal bone anomaly, 13% among those with a temporal bone anomaly, and 17% among those with BCNC stenosis. Children with BCNC stenosis had a significantly greater risk of progression in their ipsilateral ear compared with children with no stenosis: hazard ratio (HR) 2.17, 95% confidence interval (CI) (1.01, 4.66),pvalue 0.046. When we compared children with BCNC stenosis to those with normal temporal bone imaging, we found that the children with stenosis had nearly two times greater risk estimate for progression, but this difference did not reach significance, HR 1.9, CI (0.8, 4.3),p = 0.1. No children with BCNC stenosis developed hearing loss in their contralateral year by 12 months of follow-up.

Conclusion:

Children with bony cochlear nerve canal stenosis may be at increased risk for progression in their ipsilateral ear. Audiometric and medical follow-up for these children should be considered.
Complete Resection of Pancreatoblastoma With Portal Vein Obstruction After High-dose Chemotherapy: A Case Report
Authors: Ibuka Souji , Uehara Shuichiro , Ueno Takehisa , Oue Takaharu , Miyamura Takako , Hashii Yoshiko , Okuyama Hiroomi
Published: May 2017

Background:

As no standard chemotherapy exists for pancreatoblastoma (PB), surgical resection is the most effective way of achieving complete remission.

Case Report:

A 3-year-old girl with PB causing portal vein obstruction was referred to our hospital. Because of the portal vein involvement, she initially received 5 cycles of preoperative chemotherapy after biopsy, consisting of cyclophosphamide, vincristine, pirarubicin, and cisplatin. After chemotherapy, she underwent distal pancreatectomy, and the tumor was resected completely. She has been disease free for 4 years since the operation.

Conclusions:

Even in cases of advanced PB, complete surgical resection with appropriate chemotherapy can lead to complete remission.
Thalassemia Major and Priapism: A Case Report of an Adolescent
Authors: Öz Sibel , Küpeli Serhan , Sezgin Gülay , Bayram İbrahim
Published: May 2017

Priapism is defined as a prolonged pathologic penile erection without sexual stimulation. In children, priapism secondary to sickle cell disease or hematological malignancy is a frequent condition. Appropriate treatment of priapism varies; the treatment is primarily etiological, conservative management. In the present report, we aimed to present a case of asplenic thalassemia major who developed priapism, improved with hydration and ibuprofen treatment. Clinicians should take into account that priapism can be encountered in patients with thalassemia major. To our knowledge this is the second publication reporting the association between thalassemia major and priapism in childhood.
Parental Perceptions of Obesity and Obesity Risk Associated With Childhood Acute Lymphoblastic Leukemia
Authors: Jones Gary L. , McClellan Wendy , Raman Sripriya , Sherman Ashley , Guest Erin , August Keith
Published: May 2017

The prevalence of obesity and related comorbidities in survivors of childhood acute lymphoblastic leukemia (ALL) is well established and ranges anywhere from 29% to 69% depending on the study. We sought to explore the awareness of parents of survivors of childhood ALL regarding the increased risk of obesity and their perceptions regarding the overall health of their child. One hundred twenty-one parents of 99 survivors of pediatric ALL completed surveys regarding perceptions of obesity risk in survivors. Eighty percent of parents of overweight and obese survivors correctly identified their child as “a little overweight” or “overweight.” Few parents recalled discussing weight gain (21%) or obesity risk (36%) with their practitioner. Parents that did recall having these discussions and/or reported a decreased level of posttherapy activity in their child were more likely to be concerned about their child’s weight status. Improved awareness and education regarding the risk of obesity and associated comorbid conditions may provide an avenue for future prevention of obesity in survivors of pediatric ALL. Discussion and education regarding a healthy lifestyle, including proper diet and exercise, should be incorporated early in routine patient visits.
Thalidomide-induced Stroke in a Child With Thalassemia Major
Authors: Gunaseelan Sushil , Prakash Anand
Published: May 2017

β-thalassemia major is a hereditary anemia resulting from defects in β-globin production. It is also characterized by a hypercoagulable state with an increased risk of thrombosis. Thalidomide, a drug known for its immunomodulating and antiangiogenic properties, has recently been demonstrated to induce γ-globin gene expression and to increase the proliferation of erythroid cells. An increasing incidence of thromboembolic events in thalidomide-treated patients has been reported. This is often in the context of thalidomide combinations with other drugs, including steroids and particularly anthracycline-based chemotherapy, and with very low incidence of thrombosis with single-agent thalidomide treatment. We report a case of stroke in a β-thalassemic child who had received a course of thalidomide.
Clinical Assessment and Diagnostics of Patients With Hand Disorders
Authors: Leow Mabel Qi He , Lim Rebecca Qian Ru , Tay Shian Chao
Published: May 2017

Clinical assessment of the hand is important for diagnosing underlying hand disorders. Using a case study approach, the clinical assessment for three disorders of the hands is presented: trigger finger (stenosing tenosynovitis), carpal tunnel syndrome, and ulnar-sided wrist injury (styloid impingement). We assess the annular one pulley and finger range of motion for patients with trigger finger. To diagnose for carpal tunnel syndrome, assessment for Tinel's sign, Phalen's sign, abductor pollicis brevis muscle bulk, two-point discrimination, and obtaining a nerve conduction study are performed. Assessment for ulnar-sided wrist injury includes wrist range of motion, assessment of distal radial ulnar joint stability, provocation tests, grip strength, x-ray, and magnetic resonance imaging. This article begins with a description of the hand and wrist anatomy. For each case study, the clinical history is described, followed by a discussion of the pathophysiology, clinical assessments, and diagnostic tests.
The Biopsychosocial Model of Low Back Pain and Patient-Centered Outcomes Following Lumbar Fusion
Authors: Lall Maureen P. , Restrepo Elizabeth
Published: May 2017

Lumbar fusion is a surgical procedure performed to eliminate painful motion in a spinal segment by joining, or fusing, two or more vertebrae. Although the surgery has a high rate of producing radiographic fusion, many patients report pain, functional disability, an inability to return to work, and prolonged opioid pain reliever use following the procedure. Using the biopsychosocial model of low back pain as a framework, this review of the literature describes the biological, psychological, and social factors that have been associated with these negative outcomes. The findings suggest that at least some of the variability in postoperative outcomes may be due to preoperative patient characteristics, and evidence the theorized relationship between biopsychosocial factors and low back disability. The review also highlights a gap in the literature regarding biopsychosocial predictors of prolonged opioid use following lumbar fusion.
Hemosiderotic Fibrolipomatous Tumor, Pleomorphic Hyalinizing Angiectatic Tumor, and Myxoinflammatory Fibroblastic Sarcoma: Related or Not?
Authors: Boland Jennifer M. , Folpe Andrew L.
Published: May 2017

Hemosiderotic fibrolipomatous tumor is an unusual, distinctive soft tissue neoplasm with locally recurring potential, which most commonly occurs in the ankle and foot. Morphologic evidence strongly suggests that hemosiderotic fibrolipomatous tumor is related to another rare, locally aggressive tumor of the distal extremities, pleomorphic hyalinizing angiectatic tumor, with areas identical to hemosiderotic fibrolipomatous tumor seen at the periphery in most if not all pleomorphic hyalinizing angiectatic tumor. This morphologic evidence is further supported by molecular genetic data, showing recurrent TGFBR3 and/or MGEA5 rearrangements in both hemosiderotic fibrolipomatous tumor and pleomorphic hyalinizing angiectatic tumor. A possible link between hemosiderotic fibrolipomatous tumor and yet another low-grade sarcoma of the distal extremities, myxoinflammatory fibroblastic sarcoma, has also been suggested based on the occurrence of unusual examples of hemosiderotic fibrolipomatous tumor showing progression to myxoid sarcoma, demonstrating some but not all features of myxoinflammatory fibroblastic sarcoma. These “hybrid hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcoma” also commonly show TGFBR3 and/or MGEA5 rearrangements. However, classic myxoinflammatory fibroblastic sarcoma lacks areas resembling hemosiderotic fibrolipomatous tumor, and shows a very low frequency of TGFBR3 and/or MGEA5 rearrangements in prospectively diagnosed cases. This suggests that so-called “hybrid hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcoma” represents a form of malignant progression within hemosiderotic fibrolipomatous tumor, rather than a lesion strictly related to classic myxoinflammatory fibroblastic sarcoma. This article will review the morphologic features, genetic features, and differential diagnosis of these rare neoplasms, and discuss their interrelation, or lack thereof.
Critical Care Interventions for Asthmatic Patients Admitted From the Emergency Department to the Pediatric Intensive Care Unit
Authors: Cundiff Kristen Michelle , Gerard James M. , Flood Robert G.
Published: May 2017

Objectives

The aim of this study was to assess the frequency and predictors of critical interventions in asthmatic patients admitted to the pediatric intensive care unit (PICU) at a tertiary-care pediatric hospital.

Methods

We conducted a retrospective chart review of patients admitted from our emergency department (ED) to the PICU for treatment of status asthmaticus between January 1, 2008, and March 31, 2013. Patients with concomitant medical conditions and those who received a critical intervention, other than continuously aerosolized albuterol, in the ED before admission were excluded. Data collected included patient demographics, clinical characteristics including clinical asthma scores (CASs), hospital course, and adverse events.

Results

A total of 384 patients were included in the analyses (mean age, 8.2 ± 4.5 years). Thirty-four patients (8.9%) received at least 1 critical intervention. No patients were intubated, had central venous catheter placement, and developed circulatory collapse or pneumothoraxes. Independent predictors associated with an increased likelihood of receiving a critical intervention included age above 8 years (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.9–9.4), previous PICU admission (OR, 3.2; 95% CI, 1.5–6.6), altered mental status on ED arrival (OR, 4.5; 95% CI, 1.5–13.4), CAS on ED arrival of 5 or greater (OR, 3.4; 95% CI, 1.3–9.1), and CAS on PICU admission of 5 or greater (OR, 4.3; 95% CI, 1.8–10.2).

Conclusions

Patients admitted to the PICU for status asthmaticus infrequently require critical interventions if they have not been initiated in the ED. Patients with a CAS of less than 5 may be safely managed with continuously aerosolized albuterol on non–critical care units with low risk for clinical deterioration.
Assessing Dehydration Employing End-Tidal Carbon Dioxide in Children With Vomiting and Diarrhea
Authors: Freedman Stephen B. , Johnson David W. , Nettel-Aguirre Alberto , Mikrogianakis Angelo , Williamson-Urquhart Sarah , Monfries Nicholas , Cheng Adam
Published: May 2017

Objective

Serum bicarbonate reflects dehydration severity in children with gastroenteritis. Previous work in children receiving intravenous rehydration has correlated end-tidal carbon dioxide (EtCO2) with serum bicarbonate. We evaluated whether EtCO2 predicts weight change in children with vomiting and/or diarrhea.

Methods

A prospective cohort study was conducted. Eligible children were 3 months to 10 years old and presented for emergency department (ED) care because of vomiting and/or diarrhea. End-tidal carbon dioxide measurements were performed after triage. The diagnostic standard was weight change determined from serial measurements after symptom resolution. A receiver operating characteristic curve was constructed to identify a cut-point to predict 5% or more dehydration.

Results

In total, 195 children were enrolled. Among the 169 (87%) with EtCO2 measurements, the median (interquartile range [IQR]) was 30.4 (27.8 to 33.1). One hundred fifty-eight had repeat weights performed at home; the median (IQR) weight change from ED presentation to well weight was +0.06 (−0.14 to +0.30) or +0.72% (−1.2% to +2.1%). Sixteen percent (25/158) had 3% or more and 4% (6/158) had 5% or more weight gain (ie, percent dehydration). One hundred sixteen (60%) completed home follow-up and had acceptable EtCO2 recordings. Receiver operating curve analysis revealed an area under the curve of 0.34 (95% confidence interval, 0.06 to 0.62) for EtCO2 as a predictor of 5% or more dehydration.

Conclusions

The limited accuracy of EtCO2 measurement to predict 5% or more dehydration precludes its use as a tool to assess dehydration severity in children. End-tidal carbon dioxide monitoring does not have the ability to identify those children with 5% or more dehydration in a cohort of children with vomiting and/or diarrhea presenting for ED care.
Evaluation of Highest Level Pediatric Trauma Activation Criteria
Authors: Zagory Jessica A. , Wieck Minna M. , Lerner Brooke E. , Moody Suzanne , Falcone Richard A. , Burke Rita V.
Published: May 2017

Background

Despite the presence of a tiered in-hospital trauma triage system for the past decade, trauma centers still struggle with a definitive list of highest level activation criteria. In 2002, the American College of Surgeons (ACS) mandated 6 criteria for highest level activation. However, it is unknown if pediatric trauma centers follow these criteria. The purpose of this study is to identify and categorize the highest level pediatric trauma criteria used by pediatric trauma centers in the United States.

Methods

In collaboration with the ACS, we reviewed activation criteria for highest level trauma activation for all ACS-verified level I pediatric trauma centers in the United States. Criteria were sorted by 2 reviewers into categories of indicators used for activation: patient demographic, physiologic, anatomic, intervention/resource usage, mechanism, and other.

Results

A total of 51 unique criteria for highest level trauma activation were identified from 54 (96%) of 56 level I pediatric trauma centers. Each center used between 1 and 29 criteria. A total of 42.6% of pediatric trauma centers followed all 6 criteria recommended by ACS. The most commonly omitted criterion was emergency physician discretion. The most common criteria not included in the ACS recommendations, but included in the highest level activation criteria, were amputation proximal to wrist or ankle (63%), and spinal cord injury/paralysis (63%).

Conclusions

There is wide variation in the criteria used for highest level trauma activation among pediatric trauma centers. Further research investigating individual or grouped criteria to determine the most sensitive and specific criteria are necessary for appropriate triage and resource usage.
The HEADS-ED
Authors: Cappelli Mario , Zemek Roger , Polihronis Christine , Thibedeau Nathalie R. , Kennedy Allison , Gray Clare , Jabbour Mona , Reid Sarah , Cloutier Paula
Published: May 2017

Objectives

This effectiveness study aimed to evaluate the clinical use of the HEADS-ED tool for patients presenting to a pediatric emergency department (PED) for mental health (MH) care.

Methods

In this pragmatic trial, PED physicians used the HEADS-ED to guide their assessment and identify areas of MH need in 639 patients (mean [SD], 15.16 [1.40] years; female, 72.6%) who presented to the emergency department with MH concerns between May 2013 and March 2014.

Results

The HEADS-ED guided consultation to psychiatry/crisis, with 86% receiving a recommended consult. Those with a HEADS-ED score of greater than or equal to 8 and suicidality of 2 (relative risk, 2.64; confidence interval, 2.28–3.06) had a 164% increased risk of physicians requesting a consult compared with those with a score of less than 8 or greater than or equal to 8 with no suicidality of 2. The HEADS-ED mean score was significantly higher for those who received a consult (M = 6.91) than those who did not (M = 4.70; P = 0.000). Similarly, the mean score for those admitted was significantly higher (M = 7.21) than those discharged (M = 5.28; P = 0.000). Agreement on needs requiring action between PED physicians and crisis intervention workers was obtained for a subset of 140 patients and ranged from 62% to 93%.

Conclusions

Results support the HEADS-ED's use by PED physicians to help guide the assessment and referral process and for discussing the clinical needs of patients among health care providers using a common action-oriented language.
Out-of-Pocket Spending Under the Affordable Care Act for Patients With Cancer
Authors: Dixon Matthew S. , Cole Ashley L. , Dusetzina Stacie B.
Published: May 2017

The Patient Protection and Affordable Care Act (ACA) included several key provisions aimed at lowering the out-of-pocket cost burden for patients. In this review, we summarize the effect of 3 provisions under Medicaid, Medicare, and commercial insurance, respectively: expansion of Medicaid eligibility, closing the doughnut hole for Medicare Part D beneficiaries, and requiring an annual limit on out-of-pocket spending for commercially insured patients. Through this review, we find early evidence that these 3 ACA provisions have reduced the out-of-pocket burden or increased access to health insurance for many patients. Proposals to repeal and replace the ACA should consider retaining some of these important features that limit financial exposure for patients. At the same time, we have highlighted some important gaps left by the ACA that could be targeted by replacement plans. Addressing these issues may help to increase access to care and affordability for patients with cancer and without.
The Affordable Care Act and Cancer Care for Young Adults
Authors: Han Xuesong , Jemal Ahmedin
Published: May 2017

The Affordable Care Act (ACA) requires health plans that provide coverage for dependents to cover adult children to age 26 years. Extensive evidence has shown that since its implementation in September 2010 insurance coverage and access to care for young adults in the general population have increased. This article reviews the studies that have evaluated the impacts of the ACA on access to cancer care and outcomes for young adults aged 19 to 25 years. Current literature shows that the ACA increased insurance rate and cancer diagnosis at early stage for young adults. There is also evidence of the ACA’s positive effects on initiation and completion of human papillomavirus vaccination and receipt of fertility-sparing treatment for cervical cancer among young women. Several avenues of future research on the ACA and cancer care are suggested.
Norovirus and Clostridium difficile outbreaks: squelching the wildfire
Authors: Fisher Ann , Dembry Louise M.
Published: May 2017

Purpose of review

Gastrointestinal outbreaks in the healthcare setting cause increased morbidity and mortality in an already vulnerable population. Optimization of infection prevention measures can be a challenge in healthcare settings. This review describes new literature that may change the traditional infection prevention approach to such outbreaks.

Recent findings

Asymptomatic carriers of both norovirus and Clostridium difficile can pose risk of transmission to others and the environment. Rapid recognition and diagnosis can decrease the extent of an outbreak. No-touch technologies for environmental disinfection are new and effective tools. Infection prevention consultant services and systems redesign can augment efforts to control baseline infection rates and outbreaks. Antimicrobial stewardship continues to be essential to prevent C. difficile infection.

New approaches are needed to stem the tide of norovirus and C. difficile clusters and outbreaks in healthcare settings. Accurate recognition, testing, and implementation of infection prevention measures can be supported with rapid testing modalities, access to updated guidelines and no-touch disinfection systems. The work–environment culture should be carefully assessed and restructured using human engineering models to promote effective infection prevention practices. Antimicrobial stewardship initiatives are needed at the bedside and at national levels.
The evolution of care improves outcome in blunt thoracic aortic injury: A Western Trauma Association multicenter study
Authors: Shackford Steven R. , Dunne Casey E. , Karmy-Jones Riyad , Long William , Teso Desarom , Schreiber Martin A. , Watson Justin , Watson Cheri , McIntyre Robert C. , Ferrigno Lisa , Shapiro Mark L. , Southerland Kevin , Dunn Julie A. , Reckard Paul , Scalea Thomas M. , Brenner Megan , Teeter William A.
Published: May 2017

BACKGROUND

The management of blunt thoracic aortic injury (BTAI) has evolved radically in the last decade with changes in the processes of care and the introduction of thoracic endovascular aortic repair (TEVAR). These changes have wrought improved outcome, but the direct effect of TEVAR on outcome remains in question as previous studies have lacked vigorous risk adjustment and long-term follow-up. To address these knowledge gaps, we compared the outcomes of TEVAR, open surgical repair, and nonoperative management for BTAI.

METHODS

Eight verified trauma centers recruited from the Western Trauma Association Multicenter Study Group retrospectively studied all patients with BTAI admitted between January 1, 2006, and June 30, 2016. Data included demographics, comorbidities, admitting physiology, injury severity, in-hospital care, and outcome.

RESULTS

We studied 316 patients with BTAI; 57 (18.0%) were in extremis and died before treatment. Of the 259 treated surgically, TEVAR was performed in 176 (68.0%), open in 28 (10.8%), hybrid in 4 (1.5%), and nonoperative in 51 (19.7%). Thoracic endovascular aortic repair and open repair groups had similar Injury Severity Scale score, chest Abbreviated Injury Scale score, Trauma and Injury Severity Score, and probability of survival, but differed in median age (open: 28 [interquartile range {IQR}, 19–51]; TEVAR: 46 [IQR, 28–60]; p < 0.007), zone of aortic injury (p < 0.001), and grade of aortic injury (open: 6 [IQR, 4–6]; TEVAR: 2 [IQR, 2–4]; p < 0.001). The overall in-hospital mortality was 6.6% (TEVAR: 5.7%, open: 10.7%, nonoperative: 3.9%; p = 0.535). Of the 240 patients who survived to discharge, two died (one at 9 months and one at 8 years); both were managed with TEVAR, but the deaths were unrelated to the aortic procedure. Stent graft surveillance computed tomography scans were not obtained in 37.6%.

CONCLUSIONS

The mortality of BTAI continues to decrease. Thoracic endovascular aortic repair, when anatomically suitable, should be the treatment of choice. Open repair remains necessary for more proximal injuries. Process improvement in computed tomography imaging in follow-up of TEVAR is warranted.

LEVEL OF EVIDENCE

Therapeutic/care management, level III.
Suicide, guns, and buyback programs: An epidemiologic analysis of firearm-related deaths in Connecticut
Authors: Baumann Laura , Clinton Heather , Berntsson Rob , Williams Susan S. , Rovella James C. , Shapiro David , Thaker Shefali , Borrup Kevin , Lapidus Garry , Campbell Brendan T.
Published: May 2017

BACKGROUND

Gun buyback programs aim to remove unwanted firearms from the community with the goal of preventing firearm injury and death. Buyback programs are held in many communities, but evidence demonstrating their effectiveness is lacking. The purpose of this study is to compare firearms collected at buyback events to crime guns and firearms used in homicides and suicides.

METHODS

Detailed firearm and case data were obtained from the Hartford Police Department and the Office of the Chief Medical Examiner from January through December of 2015. Information was reviewed for guns collected at buyback events, crime guns confiscated by police, and for weapons associated with firearm fatalities. Detailed firearm data included type, manufacturer, model, and caliber (small, ≤ 0.32 caliber; medium, 0.357 caliber to 9 mm; large, ≥ 0.40 caliber). χ2 analyses were used for comparisons between groups.

RESULTS

In 2015, 224 crime guns were seized by the Hartford Police, 169 guns were collected at four community buyback events, and there were 187 firearm-related deaths statewide (105 suicides, 81 homicides, 1 legal intervention). Comparisons between buyback, crime, and fatality-related firearms are shown in the table below. Medium caliber handguns account for the majority of crime guns and fatalities, and buyback programs collected smaller caliber handguns. The demographics of individuals who turn in guns at buyback events and commit suicide are similar: age (buyback, 63 ± 11; suicide, 52 ± 18; homicide, 34 ± 12 years), sex (buyback, 81%; suicide, 91%; homicide, 84% men), and race (buyback, 80%; suicide, 97%; homicide, 47% white).

CONCLUSION

Handguns account for the majority of crime guns and firearm-related fatalities in Connecticut. Buyback programs are both an opportunity to remove unwanted handguns from the community and to remove firearms from the homes of individuals at increased risk of suicide.

LEVEL OF EVIDENCE

Epidemiologic/therapeutic study, level IV.
Selection of the intrinsic polarization properties of animal optical materials creates enhanced structural reflectivity and camouflage
Authors: Feller Kathryn D. , Jordan Thomas M. , Wilby David , Roberts Nicholas W.
Published: May 2017

Many animals use structural coloration to create bright and conspicuous visual signals. Selection of the size and shape of the optical structures animals use defines both the colour and intensity of the light reflected. The material used to create these reflectors is also important; however, animals are restricted to a limited number of materials: commonly chitin, guanine and the protein, reflectin. In this work we highlight that a particular set of material properties can also be under selection in order to increase the optical functionality of structural reflectors. Specifically, polarization properties, such as birefringence (the difference between the refractive indices of a material) and chirality (which relates to molecular asymmetry) are both under selection to create enhanced structural reflectivity. We demonstrate that the structural coloration of the gold beetleChrysina resplendensand silvery reflective sides of the Atlantic herring,Clupea harengusare two examples of this phenomenon. Importantly, these polarization properties are not selected to control the polarization of the reflected light as a source of visual informationper se.Instead, by creating higher levels of reflectivity than are otherwise possible, such internal polarization properties improve intensity-matching camouflage.

This article is part of the themed issue ‘Animal coloration: production, perception, function and application’.
What maintains signal honesty in animal colour displays used in mate choice?
Authors: Weaver Ryan J. , Koch Rebecca E. , Hill Geoffrey E.
Published: May 2017

Many of the colour displays of animals are proposed to have evolved in response to female mate choice for honest signals of quality, but such honest signalling requires mechanisms to prevent cheating. The most widely accepted and cited mechanisms for ensuring signal honesty are based on the costly signalling hypothesis, which posits that costs associated with ornamentation prevent low-quality males from being highly ornamented. Alternatively, by the index hypothesis, honesty can be achieved via cost-free mechanisms if ornament production is causally linked to core physiological pathways. In this essay, we review how a costly signalling framework has shaped empirical research in mate choice for colourful male ornaments and emphasize that alternative interpretations are plausible under an index signalling framework. We discuss the challenges in both empirically testing and distinguishing between the two hypotheses, noting that they need not be mutually exclusive. Finally, we advocate for a comprehensive approach to studies of colour signals that includes the explicit consideration of cost-free mechanisms for honesty.

This article is part of the themed issue ‘Animal coloration: production, perception, function and application’.
The colours of humanity: the evolution of pigmentation in the human lineage
Authors: Jablonski Nina G. , Chaplin George
Published: May 2017

Humans are a colourful species of primate, with human skin, hair and eye coloration having been influenced by a great variety of evolutionary forces throughout prehistory. Functionally naked skin has been the physical interface between the physical environment and the human body for most of the history of the genus
Homo
, and hence skin coloration has been under intense natural selection. From an original condition of protective, dark, eumelanin-enriched coloration in early tropical-dwelling
Homo
and
Homo sapiens
, loss of melanin pigmentation occurred under natural selection as
Homo sapiens
dispersed into non-tropical latitudes of Africa and Eurasia. Genes responsible for skin, hair and eye coloration appear to have been affected significantly by population bottlenecks in the course of
Homo sapiens
dispersals. Because specific skin colour phenotypes can be created by different combinations of skin colour–associated genetic markers, loss of genetic variability due to genetic drift appears to have had negligible effects on the highly redundant genetic ‘palette’ for the skin colour. This does not appear to have been the case for hair and eye coloration, however, and these traits appear to have been more strongly influenced by genetic drift and, possibly, sexual selection.

This article is part of the themed issue ‘Animal coloration: production, perception, function and application’.
Double maternal effect: duplicated nucleoplasmin 2 genes,npm2aandnpm2b, are shared by fish and tetrapods, and have distinct and essential roles in early embryogenesis
Authors: Cheung Caroline T. , Pasquier Jérémy , Bouleau Aurélien , Nguyen Thao-Vi , Chesnel Franck , Guiguen Yann , Bobe Julien
Published: May 2017

Nucleoplasmin 2(npm2) is an essential maternal-effect gene that mediates early embryonic events through its function as a histone chaperone that remodels chromatin. Here we report the existence of twonpm2(npm2aandnpm2b) genes in zebrafish. We examined the evolution ofnpm2aandnpm2bin a variety of vertebrates, their potential phylogenetic relationships, and their biological functions using knockout models via the CRISPR/cas9 system. We demonstrated that the twonpm2duplicates exist in a wide range of vertebrates, including sharks, ray-finned fish, amphibians, and sauropsids, whilenpm2awas lost in Coelacanth and mammals, as well as some specific teleost lineages. Using phylogeny and synteny analyses, we traced their origins to the early stages of vertebrate evolution. Our findings suggested thatnpm2aandnpm2bresulted from an ancient local gene duplication, and their functions diverged although key protein domains were conserved. We then investigated their functions by examining their tissue distribution in a wide variety of species and found that they shared ovarian-specific expression, a key feature of maternal-effect genes. We also showed that bothnpm2aandnpm2bare maternally-inherited transcripts in vertebrates. Moreover, we used zebrafish knockouts to demonstrate thatnpm2aandnpm2bplay essential, but distinct, roles in early embryogenesis.npm2afunctions very early during embryogenesis, at or immediately after fertilization, whilenpm2bis involved in processes leading up to or during zygotic genome activation. These novel findings will broaden our knowledge on the evolutionary diversity of maternal-effect genes and underlying mechanisms that contribute to vertebrate reproductive success.

Author Summary

The protein and transcript of thenpm2gene have been previously demonstrated as maternal contributions to embryos of several vertebrates. Recently, twonpm2genes, denoted here asnpm2aandnpm2b, were discovered in zebrafish. This study was conducted to explore the evolutionary origin and changes that occurred that culminated in their current functions. We found that an ancient local duplication of the ancestralnpm2gene created the current two forms, and while most vertebrates retained both genes, notably, mammals and certain species of fish lostnpm2aand, albeit rarely, bothnpm2aandnpm2b. Our functional analyses showed thatnpm2aandnpm2bhave diverse but essential functions during embryogenesis, asnpm2amutants failed to undergo development at the earliest stage whilenpm2bmutants developed, although abnormally, until the zygotic genome activation stage after which their development was arrested followed subsequently by death. Our study is the first to clearly demonstrate the evolution, diversification, and functional analyses of thenpm2genes, which are essential maternal factors that are required for proper embryonic development and survival.
Life stage associated remodeling of lipid metabolism regulation in the duplicated Atlantic salmon genome
Authors: Gillard Gareth , Harvey Thomas N. , Gjuvsland Arne , Jin Yang , Thomassen Magny , Lien Sigbjørn , Leaver Michael , Torgersen Jacob S. , Hvidsten Torgeir R. , Vik Jon Olav , Sandve Simen R.
Published: May 2017

Atlantic salmon migrates from rivers to sea to feed, grow and develop gonads before returning to spawn in freshwater. These habitat shifts require great phenotypic plasticity. To address the unresolved question of how the shift in diet between fresh and saltwater affects the regulation of metabolic function, we fed salmon contrasting diets in each of the two life stages. Combining transcriptomics with comparative genomics, we found that lipid metabolism undergoes a concerted shift between fresh- and saltwater stages. Lipogenesis and lipid transport become less active in liver after transition to saltwater, while genes for lipid uptake in gut are more expressed in lipid-rich seawater environments. We assess how the whole-genome duplication that gave rise to the salmonids has impacted the evolution of lipid metabolism, and find signatures of pathway-specific selection pressure on gene duplicates, as well as a limited number of cases of increased gene dosage.
Exact Topological Inference for Paired Brain NetworksviaPersistent Homology
Authors: Chung Moo K. , Villalta-Gil Victoria , Lee Hyekyoung , Rathouz Paul J. , Lahey Benjamin B. , Zald David H.
Published: May 2017

We present a novel framework for characterizing paired brain networks using techniques in hyper-networks, sparse learning and persistent homology. The framework is general enough for dealing with any type of paired images such as twins, multimodal and longitudinal images. The exact nonparametric statistical inference procedure is derived on testing monotonic graph theory features that do not rely on time consuming permutation tests. The proposed method computes the exact probability in quadratic time while the permutation tests require exponential time. As illustrations, we apply the method to simulated networks and a twin fMRI study. In case of the latter, we determine the statistical significance of the heritability index of the large-scale reward network where every voxel is a network node.
Cebranopadol blocks the escalation of cocaine intake and conditioned reinstatement of cocaine seeking in rats
Authors: de Guglielmo Giordano , Matzeu Alessandra , Kononoff Jenni , Mattioni Julia , Martin-Fardon Rémi , George Olivier
Published: May 2017

Cebranopadol is a novel agonist of nociceptin/orphanin FQ peptide (NOP) and opioid receptors with analgesic properties that is being evaluated in clinical Phase 2 and Phase 3 trials for the treatment of chronic and acute pain. Recent evidence indicates that the combination of opioid and NOP receptor agonism may be a new treatment strategy for cocaine addiction. We sought to extend these findings by examining the effects of cebranopadol on cocaine self-administration (0.5 mg/kg/infusion) and cocaine conditioned reinstatement in rats with extended access to cocaine. Oral administration of cebranopadol (0, 25, and 50 μg/kg) reversed the escalation of cocaine self-administration in rats that were given extended (6 h) access to cocaine, whereas it did not affect the self-administration of sweetened condensed milk (SCM). Cebranopadol induced conditioned place preference but did not affect locomotor activity during the conditioning sessions. Finally, cebranopadol blocked the conditioned reinstatement of cocaine seeking. These results show that oral cebranopadol treatment prevented addiction-like behaviors (i.e., the escalation of intake and reinstatement), suggesting that it may be a novel strategy for the treatment of cocaine use disorder. However, the conditioned place preference that was observed after cebranopadol administration suggests that this compound may have some intrinsic rewarding effects.
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesodermin vitro
Authors: Chal Jérome , Al Tanoury Ziad , Oginuma Masayuki , Moncuquet Philippe , Gobert Bénédicte , Miyanari Ayako , Tassy Olivier , Guevara Getzabel , Bera Agata , Sumara Olga , Garnier Jean-Marie , Kennedy Leif , Knockaert Marie , Gayraud-Morel Barbara , Tajbakhsh Shahragim , Pourquié Olivier
Published: May 2017

In vertebrates, body skeletal muscles and axial skeleton derive from the paraxial mesoderm which flanks the neural tube and notochord. The paraxial mesoderm forms in the posterior region of the embryo as presomitic mesoderm (PSM), which generates the embryonic segments called somites. Here, we characterized gene signatures identified using microarray series from the mouse PSM and compared the PSM transcriptome dynamics to that of the developing neural tube. In contrast to the PSM where an abrupt transcriptome reorganisation occurs at the level of the determination front, we show that transcriptome changes are progressive during parallel stages of neural tube differentiation. We show that these early differentiation stages of the paraxial mesoderm can be efficiently recapitulated in monolayer culturein vitrousing murine Embryonic Stem (ES) cells. We describe a serum-containing protocol which parallelsin vivotissue maturation allowing differentiation of ES cells towards a paraxial mesoderm fate. We show that R-spondin treatment or Wnt activation alone can induce posterior PSM markers in both mouse and human ES/iPS cells but acquisition of a committed posterior PSM fate requires BMP inhibition to prevent induced cells to drift to a lateral plate mesoderm identity. We show that posterior PSM-like cells induced from mouse ES cells can be further differentiatedin vitroto acquire an anterior PSMPax3-positive identity. When grafted into injured adult muscle, these induced PSM-like precursors generated large numbers of immature muscle fibers. We further show that exposing ES-derived PSM-like cells to a brief FGF inhibition step followed by culture in horse serum-containing medium allows efficient recapitulation of the myogenic program. Differentiating ES cells first produce mononucleated embryonic myocytes and subsequently multinucleated myotubes, as well as Pax7-positive cells. The protocol described here results in improved differentiation and maturation of mouse muscle fibers differentiatedin vitroover serum-free protocols. It provides an efficient system for the study of myogenic processes otherwise difficult to studyin vivosuch as fusion or satellite cell differentiation.
Differential associations of various depression-related phenotypes with cardiometabolic risks: Identification of shared genetic factors and implications for drug repositioning
Authors: Wong Brian Chi-Fung , Chau Carlos Kwan-Long , Ao Fu-Kiu , Mo Cheuk-Hei , Wong Sze-Yung , Wong Yui-Hang , So Hon-Cheong
Published: May 2017

Numerous studies have suggested associations between depression and cardiometabolic abnormalities or diseases, such as coronary artery disease and type 2 diabetes. However, little is known about the mechanism underlying this comorbidity, and whether the relationship differs by depression subtypes. Using the polygenic risk score (PRS) approach and linkage disequilibrium (LD) score regression, we investigated the genetic overlap of various depression-related phenotypes with a comprehensive panel of 20 cardiometabolic traits. GWAS results for major depressive disorder (MDD) were taken from the PGC and CONVERGE studies, with the latter focusing on severe melancholic depression. GWAS results on general depressive symptoms (DS) and neuroticism were also included. We also identified the shared genetic variants and inferred enriched pathways. In addition, we looked for drugs over-represented among the top shared genes, with an aim to finding repositioning opportunities for comorbidities.

We found significant polygenic sharing between MDD, DS and neuroticism with various cardiometabolic traits. In general, positive polygenic associations with CV risks were observed for most depression phenotypes except MDD-CONVERGE. Counterintuitively, PRS representing severe melancholic depression was associated with reduced CV risks. Enrichment analyses of shared SNPs revealed many interesting pathways, such as those related to inflammation, that underlie the comorbidity of depressive and cardiometabolic traits. Using a gene-set analysis approach, we also revealed a number of repositioning candidates, some of which were supported by prior studies, such as bupropion and glutathione. Our study highlights shared genetic bases of depression with cardiometabolic traits, and suggests the associations vary by depression subtypes. To our knowledge, this is the also first study to make use of human genomic data to guide drug discovery or repositioning for comorbid disorders.
The genetic intractability ofSymbiodinium microadriaticumto standard algal transformation methods
Authors: Chen Jit Ern , Barbrook Adrian C. , Cui Guoxin , Howe Christopher J. , Aranda Manuel
Published: May 2017

Modern transformation and genome editing techniques have shown great success across a broad variety of organisms. However, no study of successfully applied genome editing has been reported in a dinoflagellate despite the first genetic transformation ofSymbiodiniumbeing published about 20 years ago. Using an array of different available transformation techniques, we attempted to transformSymbiodinium microadriaticum(CCMP2467), a dinoflagellate symbiont of reef-building corals, with the view to performing subsequent CRISPR-Cas9 mediated genome editing. Plasmid vectors designed for nuclear transformation containing the chloramphenicol resistance gene under the control of the CaMV p35S promoter as well as several putative endogenous promoters were used to test a variety of transformation techniques including biolistics, electroporation and silicon carbide whiskers. Chloroplast-targeted transformation were attempted using an engineeredSymbiodiniumchloroplast minicircle encoding a modified PsbA protein that confers atrazine resistance. We report that we have been unable to confer chloramphenicol or atrazine resistance toSymbiodinium microadriaticumstrain CCMP2467.
Insuperable problems of the genetic code initially emerging in an RNA World
Authors: Wills Peter R , Carter Charles W
Published: May 2017

Differential equations for error-prone information transfer (template replication, transcription or translation) are developed in order to consider, within the theory of autocatalysis, the advent of coded protein synthesis. Variations of these equations furnish a basis for comparing the plausibility of contrasting scenarios for the emergence of tRNA aminoacylation, ultimately by enzymes, and the relationship of this process with the origin of the universal system of molecular biological information processing embodied in the Central Dogma. The hypothetical RNA World does not furnish an adequate basis for explaining how this system came into being, but principles of self-organisation that transcend Darwinian natural selection furnish an unexpectedly robust basis for a rapid, concerted transition to genetic coding from a peptide•RNA world.
A phylogenetic method to perform genome-wide association studies in microbes that accounts for population structure and recombination
Authors: Collins Caitlin , Didelot Xavier
Published: May 2017

Genome-Wide Association Studies (GWAS) in microbial organisms have the potential to vastly improve the way we understand, manage, and treat infectious diseases. Yet, GWAS methods established thus far remain insufficiently able to capitalise on the growing wealth of bacterial and viral genetic sequence data. Facing clonal population structure and homologous recombination, existing GWAS methods struggle to achieve both the precision necessary to reject spurious findings and the power required to detect associations in microbes. In this paper, we introduce a novel phylogenetic approach that has been tailor-made for microbial GWAS, which is applicable to organisms ranging from purely clonal to frequently recombining, and to both binary and continuous phenotypes. Our approach is robust to the confounding effects of both population structure and recombination, while maintaining high statistical power to detect associations. Thorough testing via application to simulated data provides strong support for the power and specificity of our approach and demonstrates the advantages offered over alternative cluster-based and dimension-reduction methods. Two applications toNeisseria meningitidisillustrate the versatility and potential of our method, confirming previously-identified penicillin resistance loci and resulting in the identification of both well-characterised and novel drivers of invasive disease. Our method is implemented as an open-source R package called treeWAS which is freely available athttps://github.com/caitiecollins/treeWAS.