bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk and Resilience in Pediatric Pain
Authors: Feinstein Amanda B. , Sturgeon John A. , Bhandari Rashmi P. , Yoon Isabel A. , Ross Alexandra C. , Huestis Samantha E. , Griffin Anya T. , Simons Laura E.
Published: July 2018

Objectives:

Both pediatric and parent pain catastrophizing and pain acceptance are key factors associated with pediatric pain outcomes; however, the interactive effects of these factors within the parent-child dyad have yet to be tested. The aims of this study were to examine: (1) the mediating role of child catastrophizing between parent catastrophizing and child outcomes (pain interference and mobility), (2) the mediating role of child acceptance between parent acceptance and child outcomes, and (3) whether child acceptance buffers the relation between parent catastrophizing and child catastrophizing, which in turn impacts child outcomes.

Materials and Methods:

Cross-sectional data from 324 youth with chronic pain ages 10 to 17 years (mean age=14.72, [SD=2.12]; 73.1% female; 59% Caucasian) and their parents were collected. Participants completed measures assessing pediatric Patient-Reported Outcome Measurement Information System (PROMIS) domains (mobility and pain interference), pain catastrophizing, pain acceptance, and child pain intensity. Mediation was conducted via 1000-draw bootstrap–adjusted analyses in Mplus.

Results:

Parent pain catastrophizing was indirectly associated with child pain interference via child catastrophizing but was not associated with mobility difficulties in the mediation model. Parent pain acceptance was indirectly associated with both child pain interference and mobility via child acceptance. We did not find evidence of child acceptance-buffering parent and child pain catastrophizing.

Discussion:

The findings of this study highlight the need for caregiver involvement in multidisciplinary treatments to mitigate risk and enhance resilience in youth with chronic pain.
The Effect of Axial Torsion on the Mechanical Properties of the Annulus Fibrosus
Authors: Harvey-Burgess Maxine , Gregory Diane E.
Published: July 2018

Study Design.

In-vitro study of the tissue mechanics of annulus fibrosus.

Objective.

To determine the effect of axial torsion on the mechanical properties of the inter- and intralamellar matrices.

Summary of Background Data.

Axial torsion, when combined with repetitive flexion, has been associated with an increased risk of intervertebral disc herniation. However, the mechanisms behind this relationship are poorly understood.

Methods.

Bovine intervertebral discs (IVDs) from the caudal region were exposed to a combination of either 0° or 12° of static axial torsion and 0 N or 1000 N of compression for 2 hours in an attempt to created micro-damage to the IVD. Following the loading protocol, one multilayered sample and two single layer samples were dissected from the annulus fibrosus to undergo tensile testing of the inter- and intralamellar matrices. Histological staining was also performed.

Results.

The strength of the interlamellar matrix was not affected by axial torsion or compression, suggesting that torsion did not damage the interlamellar matrix. However, intralamellar matrix strength of samples exposed to axial torsion, regardless of compressive loading magnitude, was 48% lower than those from samples that were not exposed to torsion (P < 0.001). Similarly, intralamellar matrix stiffness of samples exposed to axial torsion was 42% lower than from samples that were not exposed to torsion (P = 0.010). Additionally, histological analysis demonstrated more disruption within individual lamellae of the samples exposed to axial torsion compared with samples that were not.

Conclusion.

This study suggests that axial torsion damages the components of the intralamellar matrix as a result of the strain it puts on the matrix, thus making the intervertebral disc more susceptible to herniation.

Level of Evidence: N/A
Manual of Wiring Techniques for Orthopedic Surgery
Authors: Appleton Abraham T. , Mantz Gabriel A. , Golden-Appleton Aurora , Debenham Cai T. , Sandoval Taylor N. , Wang Qikun , Hernandez Christopher J.
Published: July 2018

Cerclage and tension band wiring techniques can be inexpensively and effectively utilized in orthopedic surgical procedures, many of which are enumerated in this article. The following cerclage wiring configurations are described and demonstrated in accompanying videos: wrapped around once and wrapped around twice patterns locked with a symmetric twist, knot twist, eyelet bend-back, or crimped double barrel sleeve; doubled symmetric twist; hairpin loop; and Mittelmeier’s double loop bend-back with twist. Tension band wiring variations are also described and illustrated. Modes of wire failure are discussed and displayed in videos. Results of previously unreported experiments measuring compression capability of a variety of wire tightening devices and cerclage configurations support the superiority of the wrapped around twice pattern over wrapped around once, symmetric twist over eyelet bend-back and knot twist, and the importance of using a finishing twist when tensioning and locking wire with a symmetric twist or doubled symmetric twist.
The Association Between Inhaled Nitric Oxide Treatment and ICU Mortality and 28-Day Ventilator-Free Days in Pediatric Acute Respiratory Distress Syndrome*
Authors: Bhalla Anoopindar K. , Yehya Nadir , Mack Wendy J. , Wilson Melissa L. , Khemani Robinder G. , Newth Christopher J. L.
Published: July 2018

Objectives:

To investigate the association between inhaled nitric oxide treatment and ICU mortality and 28-day ventilator-free days in pediatric acute respiratory distress syndrome.

Design:

Retrospective cohort study. A propensity score for inhaled nitric oxide treatment was developed and used in the analysis.

Setting:

Two quaternary care PICUs.

Patients:

Children with pediatric acute respiratory distress syndrome.

Interventions:

None.

Measurements and Main Results:

There were 499 children enrolled in this study with 143 (28.7%) receiving inhaled nitric oxide treatment. Children treated with inhaled nitric oxide were more likely to have a primary diagnosis of pneumonia (72% vs 54.8%; p < 0.001), had a higher initial oxygenation index (median 16.9 [interquartile range, 10.1–27.3] vs 8.5 [interquartile range, 5.8–12.2]; p < 0.001), and had a higher 72-hour maximal Vasoactive-Inotrope Score (median 15 [interquartile range, 6–25] vs 8 [interquartile range, 0–17.8]; p < 0.001) than those not receiving inhaled nitric oxide. Mortality was higher in the inhaled nitric oxide treatment group (25.2% vs 16.3%; p = 0.02), and children in this group had fewer 28-day ventilator-free days (10 d [interquartile range, 0–18 d] vs 17 d (interquartile range 5.5–22 d]; p < 0.0001). We matched 176 children based on propensity score for inhaled nitric oxide treatment. In the matched cohort, inhaled nitric oxide treatment was not associated with mortality (odds ratio, 1.3 [95% CI, 0.56–3.0]) or 28-day ventilator-free days (incidence rate ratio, 0.91 [95% CI, 0.80–1.04]). These results remained consistent in the entire study cohort when the propensity score for inhaled nitric oxide treatment was used for either inverse probability weighting or stratification in regression modeling with the exception that subjects treated with inhaled nitric oxide were more likely to have 0 ventilator-free days (p ≤ 0.02). In secondary analysis stratified by oxygenation response, inhaled nitric oxide treatment was not associated with mortality or 28-day ventilator-free days in children with a positive oxygenation response (all p > 0.2)

Conclusions:

Treatment with inhaled nitric oxide in pediatric acute respiratory distress syndrome is not associated with improvement in either mortality or ventilator-free days and may be associated with harm. Further prospective trials are required to define the role of inhaled nitric oxide treatment in pediatric acute respiratory distress syndrome.
Emerging Nonsurgical Therapies for Locally Advanced and Metastatic Nonmelanoma Skin Cancer
Authors: Chen Leon , Aria Alexander B. , Silapunt Sirunya , Migden Michael R.
Published: July 2018

BACKGROUND

Locally advanced and metastatic nonmelanoma skin cancer (NMSC) not amenable to surgical resection requires a different approach to therapy.

OBJECTIVE

To review the efficacy and adverse effects of emerging treatment options for locally advanced and metastatic NMSC.

MATERIALS AND METHODS

A comprehensive search on PubMed was conducted to identify relevant literature investigating the role of program cell death 1 (PD-1) inhibitor, cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor, epidermal growth factor receptor (EGFR) inhibitor, and Hedgehog pathway inhibitors in the treatment of NMSC.

RESULTS

PD-1 inhibitor and CTLA-4 inhibitor have shown promising efficacy with tolerable side-effect profiles in the treatment of NMSC, although the number of cases reported is limited. Currently, 3 larger-scale clinical trials are investigating PD-1 inhibitor therapy for NMSC. Similarly, EGFR inhibitor demonstrated marginal success in unresectable cutaneous squamous cell carcinomas. Hedgehog pathway inhibitors were approved by the US FDA for treatment of locally advanced and metastatic basal cell carcinomas and have shown favorable efficacy. Common adverse effects included muscle spasm, alopecia, and dysgeusia.

CONCLUSION

Systemic therapies including PD-1 inhibitors and CTLA-4 inhibitors have demonstrated early promising results for difficult-to-treat NMSC. Future studies are necessary to optimize treatment outcome.
Epidermal Fluence Threshold Determination by Real-Time Melanin Measurements
Authors: Lloyd Amanda Abramson , Graves Michael S. , Ross Edward V.
Published: July 2018

BACKGROUND AND OBJECTIVE

Epidermal preservation is essential during laser treatment for vascular, hair, and benign pigment dyschromias. Epidermal tolerance is determined by epidermal melanin content, fluence, pulse width, wavelength, skin cooling, and spot size. The authors' objective was to determine the maximum epidermal tolerance for the long-pulse alexandrite 755 nm and the long-pulse neodymium-doped yttrium aluminum garnet (Nd:YAG) 1064-nm lasers for varying epidermal melanin content.

MATERIALS AND METHODS

Skin melanin measurements were performed at the test sites with a melanin reader, and 0.5 to 1 second of refrigerated air precooled the skin. Then, alexandrite and Nd:YAG laser test spots of 5 to 18 mm were delivered in a series of ascending fluences using 5-, 20-, and 50-ms pulse widths. Skin response at 24 to 48 and 96 hours was scored from 0 to 15 varying from “no reaction” to “severe scabbing.”

RESULTS

Alexandrite laser, mean threshold fluences increased by a factor of 1.2 increasing from 5 to 20 ms, and by a factor of 1.4 increasing from 5 to 50 ms, among subjects with a melanin index (MI) from 9 to 25 (Fitzpatrick skin phototype I-III). The Nd:YAG fluence to reach epidermal tolerance was 6X the fluence with the alexandrite laser for the same MI in subjects with MI 26 to 35.

CONCLUSION

Epidermal melanin measurements are quantitative and objective, therefore, improving treatment setting determination by decreasing the risk of overtreatment or undertreatment.
AMPLITUDE LOSS OF THE HIGH-FREQUENCY FLICKER ELECTRORETINOGRAM IN EARLY DIABETIC RETINOPATHY
Authors: McAnany J. Jason , Park Jason C. , Chau Felix Y. , Leiderman Yannek I. , Lim Jennifer I. , Blair Norman P.
Published: July 2018

Purpose:

To evaluate retinal dysfunction in diabetic patients who have mild or no nonproliferative diabetic retinopathy (DR) using the high-frequency flicker electroretinogram.

Methods:

Light-adapted flicker electroretinograms were recorded from 15 diabetic patients who have no clinically apparent retinopathy, 15 diabetic patients who have mild nonproliferative DR, and 15 nondiabetic, age-equivalent controls. Electroretinograms were elicited by full-field flicker at 2 temporal frequencies, 31.25 and 62.5 Hz, and were recorded using conventional techniques. Amplitude and timing of the flicker responses were compared among the groups and correlated with clinical characteristics including age, acuity, disease duration, and HbA1c.

Results:

The 31.25-Hz flicker amplitude was slightly, but nonsignificantly, smaller for subjects with no DR and mild nonproliferative DR , compared with the control group (both t < 1.38, P > 0.31); small, nonsignificant response delays for both patient groups were also observed (both t < 1.57, P > 0.12). By contrast, there were significant amplitude reductions for the 62.5-Hz flicker stimulus: mean amplitude was reduced by 32% for subjects with no DR and by 41% for subjects with mild nonproliferative DR (both t > 2.92 and P < 0.01). Response timing at 62.5 Hz did not differ significantly from control for either group (both t < 1.2 and P > 0.39). Electroretinogram amplitude and timing were not correlated significantly with clinical characteristics.

Conclusion:

The 62.5-Hz flicker electroretinogram is useful for evaluating retinal dysfunction in diabetic patients who have mild or no DR because this response can be significantly reduced. Attenuation of the high-frequency flicker electroretinogram, which is primarily generated by bipolar cells, suggests a relatively early retinal site of neural dysfunction.
Nonpharmacological Management of Persistent Pain in Elite Athletes: Rationale and Recommendations
Authors: Moseley G. Lorimer , Baranoff John , Rio Ebonie , Stewart Mike , Derman Wayne , Hainline Brian
Published: July 2018

Persistent pain is common in elite athletes. The current review arose from a consensus initiative by the International Olympic Committee to advance the development of a standardized, scientific, and evidence-informed approach to management. We suggest that optimal management of persistent pain in elite athletes requires an understanding of contemporary pain science, including the rationale behind and implementation of a biopsychosocial approach to care. We argue that athletes and clinicians need to understand the biopsychosocial model because it applies to both pain and the impact of pain with special reference to the sport setting. Management relies on thorough and precise assessment that considers contributing factors across nociceptive, inflammatory, neuropathic, and centrally acting domains; these can include contextual and psychosocial factors. Pain management seeks to remove contributing factors wherever possible through targeted education; adjustment of mechanical loading, training, and performance schedules; psychological therapies; and management of inflammation.
Audiologic Manifestations of Marshall Syndrome
Authors: Bacciu Andrea , Di Lella Filippo , Iaccarino Ilaria , Pasanisi Enrico , Fava Giovanni , Vincenti Vincenzo , Falcioni Maurizio
Published: July 2018

Objective:

Marshall syndrome is a genetic disorder caused by mutations in the COL11A1 gene. This syndrome is characterized by skeletal, ophthalmologic, craniofacial, and auditory abnormalities. Hearing loss is among the main manifestations reported in this disorder being observed in approximately 80% of affected individuals.

The present study aims to describe the audiologic characteristics of three members of a family with Marshall syndrome and also serves as a review of the literature.

Study Design:

Family study.

Setting:

Tertiary care otology and skull base center.

Patients:

We report the audiologic findings in a family with Marshall syndrome consisting of a mother and her son and daughter.

Intervention(s): :

The audiologic evaluation included tympanometry, acoustic reflexes testing, auditory brainstem response, transient otoacoustic emissions, pure-tone audiometry, speech audiometry in quiet, and conditioned play audiometry. These methods were applied according to the age of the patients. In addition, we provide a review of the English-language literature in an attempt to clarify the auditory phenotype of this syndrome.

Results:

All 3 affected individuals had heterozygous c.3816+1G>A mutation in the splicing donor site of intron 50 of the COL11A1 gene. All three patients in our study had bilateral sensorineural hearing loss. Hearing impairment ranged from mild to moderate in the daughter, moderate in the son, and from mild to moderate in their mother.

Conclusion:

The majority of individuals with Marshall syndrome present early-onset bilateral sensorineural hearing loss. Hearing impairment is usually detected in early childhood, progresses gradually, and becomes stable in late adulthood, with a severity ranging from mild to severe.
The Epidemiology of Vestibular Migraine: A Population-based Survey Study
Authors: Formeister Eric J. , Rizk Habib G. , Kohn Michael A. , Sharon Jeffrey D.
Published: July 2018

Objectives:

1. Describe the epidemiology of vestibular migraine (VM) in the United States, using data from the 2008 National Health Interview Survey (NHIS). 2. Characterize the sociodemographic and clinical attributes of people with VM.

Study Design:

Population-based nationwide survey study of US adults.

Patients:

Adult respondents to the 2008 NHIS.

Main Outcome Measures:

The responses of participants in the 2008 NHIS balance and dizziness supplement (n = 21,781) were analyzed using statistical software. A case definition for VM was generated based on consensus criteria for diagnosis, and this was applied to the dataset to ascertain the prevalence, demographic, and clinical characteristics of VM.

Results:

The 1-year prevalence of a dizziness or balance problem in the United States was 11.9% (2,490 respondents). Of respondents with dizziness, 584 (23.4%) met our case definition of VM, which represents a prevalence of VM in 2.7% of adults. There was a female preponderance (64.1%) and a slightly younger mean age (40.9 yr) for those with VM as compared with all respondents (51.7% females and 46.0 yr, respectively). Multivariate analysis showed that age less than 40, female sex, anxiety, depression, and prior head trauma were all associated with significantly increased odds of experiencing VM. Only 10% of subjects meeting criteria for VM were told that migraine was the cause of their dizziness.

Conclusion:

Using a representative database, we found a much higher prevalence of VM in the United States than previously reported. Results from this study indicate likely under-diagnosis of VM.
Lipid-driven immunometabolic responses in atherosclerosis
Authors: Gisterå Anton , Ketelhuth Daniel F.J.
Published: July 2018

Purpose of review

Atherosclerosis is a chronic inflammatory disease in which subendothelial infiltration of lipoproteins leads to inflamed lesions in arteries. Despite improvements in secondary prevention, most cardiovascular events cannot be avoided with current therapies. This review focuses on novel mechanistic insights on lipid-driven immune activation, which could pave the way for new anti-inflammatory treatments for atherosclerosis.

Recent findings

Immunometabolic interactions can shape the immune response. Within atherosclerotic plaques, macrophages and T cells are the dominant immune cell populations. Using multiple mechanisms, lipoprotein-derived components activate both the innate and adaptive immune systems. Cholesterol crystals and apolipoprotein B-peptides have been shown to activate macrophages and T cells, respectively. Lipoproteins are also important modulators of regulatory T cells that can hamper vascular inflammation. In the liver, T cells can influence hepatic inflammation and lipoprotein metabolism. Hence, there is an intricate crosstalk between the immune system and lipoprotein metabolism.

Novel treatments are needed to prevent clinical manifestations of atherosclerosis. Improved understanding of lipid-driven immunometabolic responses is likely to reveal new therapeutic targets.
Cardiovascular disease in Noonan syndrome
Authors: Pierpont Mary Ella , Digilio Maria Cristina
Published: July 2018

Purpose of review

To provide information on the scope of cardiac disease in Noonan syndrome.

Recent findings

Noonan syndrome is a common autosomal dominant RASopathy disorder characterized by clinical findings of facial dysmorphism, congenital heart disease, and short stature. The degree of genetic heterogeneity has recently become evident in that Noonan syndrome is now known to be caused by mutations in a large variety of genes which produce dysregulation of the RAS–MAPK (mitogen-activated protein kinase) signaling pathway. The scope of cardiac disease in Noonan syndrome is quite variable depending on the gene mutation, with some mutations usually associated with a high incidence of congenital heart defects (PTPN11,KRAS, and others) while those with predominantly hypertrophic cardiomyopathy (HCM) have higher risk and morbidity profiles (RAF1,RIT1, and those associated with multiple lentigines).

Cardiac disease in Noonan syndrome varies according to the type of gene mutation. The most common forms of cardiac disease include pulmonary stenosis, HCM, and atrial septal defect. HCM in general is associated with increased risk, mortality, and morbidity. New concepts for potential treatments are discussed.
NordiQC Assessments of MSH6 Immunoassays
Authors: Vyberg Mogens , Røge Rasmus , Bzorek Michael , Nielsen Ole
Published: July 2018

This paper is number 4 in a series developed through a partnership between ISIMM and Nordic immunohistochemical Quality Control for the purpose of reporting research assessing the performance characteristics of immunoassays in an external proficiency testing program.
Major Adverse Events Following Over-Shunting Are Associated With Worse Outcomes Than Major Adverse Events After a Blocked Systemic-to-Pulmonary Artery Shunt Procedure
Authors: Soo Kok Wai , Brink Johann , d’Udekem Yves , Butt Warwick , Namachivayam Siva P.
Published: July 2018

Objectives:

Causes of major adverse event after systemic-to-pulmonary shunt procedure are usually shunt occlusion or over-shunting. Outcomes categorized on the basis of these causes will be helpful both for quality improvement and prognostication.

Design:

Retrospective cohort analysis of children who underwent a systemic-to-pulmonary shunt after excluding those who had it for Norwood or Damus-Kaye-Stansel procedure.

Setting:

The Royal Children’s Hospital, Melbourne, VIC, Australia.

Patients:

From 2008 to 2015, 201 children who had a systemic-to-pulmonary shunt were included.

Interventions:

Major adverse event is defined as one or more of cardiac arrest, chest reopening, or requirement for extracorporeal membrane oxygenation. Study outcome is a “composite poor outcome,” defined as one or more of acute kidney injury, necrotizing enterocolitis, brain injury, or in-hospital mortality.

Measurements and Main Results:

Median (interquartile range) age was 12 days (6–38 d) and median (interquartile range) time to major adverse event was 5.5 hours (2–17 hr) after admission. Overall, 36 (18%) experienced a major adverse event, and reasons were over-shunting (n = 17), blocked shunt (n = 13), or other (n = 6). Fifteen (88%) in over-shunting group suffered a cardiac arrest compared with two (15%) in the blocked shunt group (p < 0.001). The composite poor outcome was seen in 15 (88%) in over-shunting group, four (31%) in the blocked shunt group, and 56 (34%) in those who did not experience a major adverse event (p < 0.001). By multivariable analysis, predictors for composite poor outcome were major adverse event due to over-shunting (no major adverse event—reference; over-shunting odds ratio, 18.60; 95% CI, 3.87–89.4 and shunt-block odds ratio, 1.57; 95% CI, 0.46–5.35), single ventricle physiology (odds ratio, 4.70; 95% CI, 2.34–9.45), and gestation (odds ratio, 0.84/wk increase; 95% CI, 0.74–0.96).

Conclusions:

Infants who suffer major adverse event due to over-shunting experience considerably poorer outcomes than those who experience events due to shunt block. A mainly hypoxic event with maintenance of systemic perfusion (as often seen in a blocked shunt) is less likely to result in poorer outcomes than those after a hypoxic-ischemic event (commonly seen in over-shunting).
Expression of Laminin Receptor 1 in Normal, Hyperplastic, and Malignant Endometrium
Authors: Kurdoglu Mertihan , Kucukaydin Zehra , Kurdoglu Zehra , Bulut Gulay , Unlu Yasar , Ozen Suleyman
Published: July 2018

Laminin receptor 1 may have a role in the progression from endometrial hyperplasia with or without atypia to endometrial cancer. Therefore, we aimed to investigate the pattern, percentage, and intensity of laminin receptor 1 expression in normal, hyperplastic, and neoplastic endometrium. Paraffin blocks of 131 specimens with the diagnoses of normal endometrium (n=25), endometrial hyperplasia with atypia (n=21) or without atypia (n=55), and endometrial cancer (n=30) were immunostained with laminin receptor 1 antibody, and its expression percentage, pattern, and intensity in the epithelial cytoplasm, basement membrane, and endometrial stroma of these tissues were assessed. When compared with hyperplasia with or without atypia and endometrial cancer, the percentage of nonstaining with laminin receptor 1 in the epithelial basement membrane was higher (96%), and the percentage of <50% staining with laminin receptor 1 was lower (4%) in the normal endometrium (P=0.001). While a progressive increment in staining percentage and density of epithelial cytoplasm and basement membrane was noted through an orderly progression from normal endometrium to endometrial hyperplasia without atypia, endometrial hyperplasia with atypia, and cancer of endometrium (P<0.001), such a relationship was not found for the staining percentage and density of endometrial stroma (P>0.05). Disease progression–related gradual increment in laminin receptor 1 expression in the epithelial basement membranes of hyperplastic endometrium with or without atypia and cancer of endometrium reveals that it may play a substantial role in the transition from premalignant to the malignant state of endometrial lesions.
A Cell Line–based Immunohistochemical p53 Expression Pattern Control Panel
Authors: Hussain Imran , Howard Robin S. , Syed Viqar , Allgäuer Michael , Gong Heping , Xing Deyin , Andersen John D.
Published: July 2018

TP53 gene mutations are known to manifest in distinct p53 immunohistochemical staining patterns; overexpression, wild-type, and null. These stratified staining patterns are routinely utilized in subtyping ovarian cancer subtypes. Three ovarian cancer cell lines were used in the construction of an immunohistochemical p53 expression pattern control panel that highlight respective TP53 mutation status. The cell line control panel sections demonstrated consistent clean and easily interpretable p53 immunohistochemical staining. Procured resection, biopsy, and cytologic specimens were submitted along with either standard control tissue or a p53 cell line control panel to pathologists of varying experience for interrater reliability analysis. Individual interrater reliability was near-perfect and was improved with the p53 cell line control panel when compared with the tissue control. The cell line control panel demonstrated decreased misinterpretation of null expression pattern as wild-type. Next-generation sequencing analysis was performed on the cell lines and select cases, in which there was discordance in p53 expression pattern interpretation. Next-generation sequencing analysis demonstrated low-frequency variant mutations in some cases in which there was reviewer discordance. This study suggests the addition of a p53 cell line expression pattern control panel could potentially increase p53 interpretation accuracy for ovarian cancer subtypes. We developed a cell line–based p53 control panel that has the potential to increase individual interrater reliability for p53 immunohistochemical expression pattern determination, support immunohistochemical optimization, and direct submission of difficult to interpret p53 staining cases to next-generation sequencing.
Chronic Family Stress and Adolescent Health: The Moderating Role of Emotion Regulation
Authors: Jones Emily J. , Lam Phoebe H. , Hoffer Lauren C. , Chen Edith , Schreier Hannah M.C.
Published: July 2018

Objective

The aim of the study was to assess whether the association between chronic family stress and physiological measures is moderated by emotion regulation strategies in an adolescent sample.

Methods

Chronic family stress was assessed via a semistructured interview and emotion regulation strategies (cognitive reappraisal and suppression) via questionnaire among 261 adolescents (14.57 (1.07) years). Several metabolic (waist-hip ratio, systolic and diastolic blood pressure) and inflammatory markers (basal and stimulated proinflammatory cytokine production in response to bacterial challenge) as well as glucocorticoid sensitivity were assessed.

Results

There were no main effects of chronic family stress, cognitive reappraisal, or suppression on physiological measures (all p's > .10). Emotion regulation moderated the association between chronic family stress and physiological measures. As chronic family stress increased, adolescents higher in cognitive reappraisal had smaller waist-hip ratios (B = −.003, SE = .001, p = .015) and lower systolic blood pressure (B = −.303, SE = .143, p = .035), although no moderation was found with respect to inflammatory markers and glucocorticoid sensitivity (all p's > .30). In addition, as chronic family stress increased, adolescents higher in suppression showed evidence of higher stimulated proinflammatory cytokine production (B = .046, SE = .020, p = .021) and lower glucocorticoid sensitivity (B = .051, SE = .021, p = .015), although basal inflammation and metabolic measures were not moderated by suppression (all p's > .50).

Conclusions

This study suggests that the types of emotion regulation strategies used by adolescents may affect the extent to which chronic family stress affects important metabolic and immune processes.
What Can Apologies in the Electronic Health Record Tell Us About Health Care Quality, Processes, and Safety?
Authors: Matulis John C. , North Frederick
Published: July 2018

Introduction

Apologizing to patients is an encouraged practice, yet little is known about how and why providers apologize and what insights apologies could provide in improving quality and safety.

Objective

The aim of the study was to determine whether provider apologies in the electronic health record could identify patient safety concerns and opportunities for improvement.

Methods

After performing a free-text search, we randomly selected 100 clinical notes from 1685 available containing terminology related to apology. We categorized the reason for apology, presence and classification of medical error, level of patient harm, and practice improvement opportunities. We compared patient events discovered from apologies in the medical record to standard patient incident report logs.

Results

Of 100 randomly selected apologies, 37 were related to a delay in care, 14 to misunderstanding, 11 to access to care, and 8 to information technology. For apologies related to delay, the median delay was 6 days (mean = 8.9, range = 0–41). Twenty-four (65%) of the 37 delays were related to diagnostic testing.

Medical errors were associated with 46 (46%) of the 100 apologies. Sixty-four (64%) of the 100 apologies were associated with actionable opportunities for improvement. These opportunities were classified into 37 discrete issues across 8 broad categories. When apology review was compared with standard incident report logs, 27 (73%) of the 37 discrete issues identified by patient apology review were not found in incident reporting; both methods identified similar rates of patient harm.

Conclusions

Review of apologies in the electronic health record can identify patient safety concerns and improvement opportunities not apparent through standard incident reporting.
Reconstruction of Contracted Eye Socket With Autogenic Dermal Sphere Connected to Epidermis
Authors: Tian Rui , Xu Haitao , Huang Xinyu , Wang Xingxing , Zhang Jialu , Du Yuanyuan
Published: July 2018

Background:

Because of the deficiency of blood circulation and soft tissue, reconstruction of the eye socket for severe conjunctival sac stenosis in anophthalmic patients is very difficult. In this article, the authors report an innovative technique for conducting a 1-stage operation to reconstruct the contracted eye socket with an autogenic dermal sphere connected to the epidermis (ADSE).

Methods:

Five patients, each having a single severely contracted eye socket and conjunctival sac, were included in this study. An ADSE was transplanted into the contracted eye socket and conjunctival sac. After the operation, several observation indexes were evaluated, such as the survival and stability of implanted autologous tissue, the improvement of the contracted eye socket, and the degree of patients’ satisfaction with their appearance.

Results:

All of the implanted epidermal and dermal tissues survived well after 6 months’ observation. Although somewhat absorbed, the transplanted dermal ball was plump in the eye socket, and the epithelial tissues merged well with the residual conjunctival epithelium. Moreover, the transplanted epidermis assumed a mucosal appearance in 4 of 5 patients. After reconstruction of the eye socket, the size of the conjunctival sac and depth of the eye socket were corrected sufficiently for patients to wear an ocular prosthesis.

Conclusions:

The implantation of an ADSE can reconstruct a severely contracted eye socket in anophthalmic patients. Because of the high survival rate and limited absorption ratio, this 1-stage operation satisfied both patients and their ophthalmologists.
Sinusitis Due to the Presence of a Dental Implant Inside the Maxillary Sinus
Authors: Conforte Jadison Junio , Ponzoni Daniela
Published: July 2018

The migration of a dental implant into the maxillary sinus is an uncommon event of occurrence. Disrespect for concepts of implantology, low alveolar bone density at the site, high incidence of masticatory force in posterior region, and clinical intercurrences predispose to failure in rehabilitation.
Emergency general surgery in the United Kingdom: A lot of general, not many emergencies, and not much surgery
Authors: Ramsay George , Wohlgemut Jared M. , Jansen Jan O.
Published: July 2018

BACKGROUND

The provision of emergency general surgery services is a global issue, with important implications for patients and workforce. The aim of this study was to analyze the characteristics of emergency general surgical patients in the United Kingdom, with reference to diagnostic case mix, operative workload, comorbidity, discharge destination, and outcomes, to facilitate comparisons and future service development.

METHODS

This is a cross-sectional population-based study based in the National Health Service in Scotland, one of the home nations of the United Kingdom. All patients aged 16 or older admitted under the care of a general surgeon, as an emergency, to a National Health Service hospital in Scotland, in 2016, were included.

RESULTS

There were 81,446 emergency general surgery admissions by 66,498 patients. Median episode age was 53 years. There were more female patients than male (55% vs 45%, p < 0.0001). The most common diagnoses were nonspecific abdominal pain (20.2%), cholecystitis (7.2%), constipation (3.4%), pancreatitis (3.1%), diverticular disease (3.1%), and appendicitis (3.1%). Only 25% of patients had operations (n = 20,292). The most frequent procedures were appendicectomy (13.1%), endoscopy (11.3%), and drainage of skin lesions (9.7%). Diagnoses and operations differed with age. Overall median length of stay was 1 day. With a 6-month follow-up, patients older than 75 years had a 19.8% mortality rate.

CONCLUSIONS

Emergency general surgery in the United Kingdom is a high-volume, diagnostically diverse, and low–operative volume specialty with high short-term mortality rate in elderly patients. Consideration should be given to alternative service delivery models, which make better use of surgeons’ skills while also ensuring optimal care for patients who are increasingly elderly and have complex chronic health problems.

LEVEL OF EVIDENCE

Epidemiologic study, level III.
A Review of the Effects of Transcranial Direct Current Stimulation for the Treatment of Hallucinations in Patients With Schizophrenia
Authors: Mondino Marine , Sauvanaud Florence , Brunelin Jérôme
Published: July 2018

Some 25% to 30% of patients with schizophrenia report auditory verbal hallucinations (AVHs) that fail to respond adequately to antipsychotic treatments. In such cases, transcranial direct current stimulation (tDCS) has been proposed as a therapeutic option. Here, we aim to provide an exhaustive review of the literature examining the clinical effects of tDCS on AVH in patients with schizophrenia. A systematic search in the PubMed and Web of Science databases yielded 14 results, 7 randomized controlled trials (RCTs) and 7 open-label studies. Among them, 4 RCTs and 7 open-label studies reported a significant reduction of AVH after repeated sessions of tDCS, whereas 3 RCTs did not show any advantage of active tDCS over sham tDCS. Altogether, current studies showed an overall decrease of approximately 26% of AVH after active tDCS and 11% after sham tDCS. One suitable approach to decreasing AVH was to deliver twice-daily sessions of tDCS over 5 consecutive days (10 sessions at 20 minutes each, 2 mA) with the anode over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Demographic and clinical parameters such as young age, nonsmoking status, and higher frequencies of AVH occurrence seemed to be predictors of clinical improvement. Further RCTs, with larger sample sizes, are needed to confirm the usefulness of tDCS for AVH.
CRISPR-bind: a simple, custom CRISPR/dCas9-mediated labeling of genomic DNA for mapping in nanochannel arrays
Authors: Zhang Denghong , Chan Saki , Sugerman Kenneth , Lee Joyce , Lam Ernest T. , Bocklandt Sven , Cao Han , Hastie Alex R.
Published: July 2018

Bionano genome mapping is a robust optical mapping technology used for de novo construction of whole genomes using ultra-long DNA molecules, able to efficiently interrogate genomic structural variation. It is also used for functional analysis such as epigenetic analysis and DNA replication mapping and kinetics. Genomic labeling for genome mapping is currently specified by a single strand nicking restriction enzyme followed by fluorophore incorporation by nick-translation (NLRS), or by a direct label and stain (DLS) chemistry which conjugates a fluorophore directly to an enzyme-defined recognition site. Although these methods are efficient and produce high quality whole genome mapping data, they are limited by the number of available enzymes—and thus the number of recognition sequences—to choose from. The ability to label other sequences can provide higher definition in the data and may be used for countless additional applications. Previously, custom labeling was accomplished via the nick-translation approach using CRISPR-Cas9, leveraging Cas9 mutant D10A which has one of its cleavage sites deactivated, thus effectively converting the CRISPR-Cas9 complex into a nickase with customizable target sequences. Here we have improved upon this approach by using dCas9, a nuclease-deficient double knockout Cas9 with no cutting activity, to directly label DNA with a fluorescent CRISPR-dCas9 complex (CRISPR-bind). Unlike labeling with CRISPR-Cas9 D10A nickase, in which nicking, labeling, and repair by ligation, all occur as separate steps, the new assay has the advantage of labeling DNA in one step, since the CRISPR-dCas9 complex itself is fluorescent and remains bound during imaging. CRISPR-bind can be added directly to a sample that has already been labeled using DLS or NLRS, thus overlaying additional information onto the same molecules. Using the dCas9 protein assembled with custom target crRNA and fluorescently labeled tracrRNA, we demonstrate rapid labeling of repetitive DUF1220 elements. We also combine NLRS-based whole genome mapping with CRISPR-bind labeling targeting Alu loci. This rapid, convenient, non-damaging, and cost-effective technology is a valuable tool for custom labeling of any CRISPR-Cas9 amenable target sequence.
Human hippocampal theta oscillations reflect sequential dependencies during spatial planning
Authors: Kaplan Raphael , Campo Adrià Tauste , Bush Daniel , King John , Principe Alessandro , Koster Raphael , Ley-Nacher Miguel , Rocamora Rodrigo , Friston Karl J.
Published: July 2018

Movement-related theta oscillations in rodent hippocampus coordinate ‘forward sweeps’ of location-specific neural activity that could be used to evaluate spatial trajectories online. This raises the possibility that increases in human hippocampal theta power accompany the evaluation of upcoming spatial choices. To test this hypothesis, we measured neural oscillations during a spatial planning task that closely resembles a perceptual decision-making paradigm. In this task, participants searched visually for the shortest path between a start and goal location in novel mazes that contained multiple choice points, and were subsequently asked to make a spatial decision at one of those choice points. We observed ~4-8 Hz hippocampal/medial temporal lobe theta power increases specific to sequential planning that were negatively correlated with subsequent decision speed, where decision speed was inversely correlated with choice accuracy. These results implicate the hippocampal theta rhythm in decision tree search during planning in novel environments.
Mutations in microRNA processing genes in Wilms tumors derepress theIGF2regulatorPLAG1
Authors: Chen Kenneth S. , Stroup Emily K. , Budhipramono Albert , Rakheja Dinesh , Nichols-Vinueza Diana , Xu Lin , Stuart Sarai H. , Shukla Abhay A. , Fraire Claudette , Mendell Joshua T. , Amatruda James F.
Published: July 2018

Many childhood Wilms tumors are driven by mutations in the microRNA biogenesis machinery, but the mechanism by which these mutations drive tumorigenesis is unknown. Here we show that the transcription factorpleomorphic adenoma gene 1 (PLAG1) is a microRNA target gene that is overexpressed in Wilms tumors with mutations in microRNA processing genes. Wilms tumors can also overexpressPLAG1through copy number alterations, andPLAG1expression correlates with prognosis in Wilms tumors.PLAG1overexpression accelerates growth of Wilms tumor cells in vitro and induces neoplastic growth in the developing mouse kidney in vivo. In both settings,PLAG1transactivatesinsulin-like growth factor 2(IGF2), a key Wilms tumor oncogene, and drives mammalian target of rapamycin complex 1 (mTORC1) signaling. These data link microRNA impairment to the PLAG1–IGF2 pathway, providing new insight into the manner in which common Wilms tumor mutations drive disease pathogenesis.
A credibility-based yield forecasting model for crop reinsurance pricing and weather risk management
Authors: Zhu Wenjun , Porth Lysa , Tan Ken Seng
Published: July 2018

Purpose

The purpose of this paper is to propose an improved reinsurance pricing framework, which includes a crop yield forecasting model that integrates weather variables and crop production information from different geographically correlated regions using a new credibility estimator, and closed form reinsurance pricing formulas. A yield restatement approach to account for changing crop mix through time is also demonstrated.

Design/methodology/approach

The new crop yield forecasting model is empirically analyzed based on detailed farm-level data from Manitoba, Canada, covering 216 crop varieties from 19,238 farms from 1996 to 2011. As well, corresponding weather data from 30 stations, including daily temperature and precipitation, are considered. Algorithms that combine screening regression, cross-validation and principal component analysis are evaluated for the purpose of achieving efficient dimension reduction and model selection.

Findings

The results show that the new yield forecasting model provides significant improvements over the classical regression model, both in terms of in-sample and out-of-sample forecasting abilities.

Research limitations/implications

The empirical analysis is limited to data from the province of Manitoba, Canada, and other regions may show different results.

Practical implications

This research is useful from a risk management perspective for insurers and reinsurers, and the framework may also be used to develop improved weather risk management strategies to help manage adverse weather events.

Originality/value

This is the first paper to integrate a credibility estimator for crop yield forecasting, and develop a closed form reinsurance pricing formula.
Two Novel Methods for Enhancing Postmortem Fingerprint Recovery from Mummified Remains
Authors: Morgan Lee O. , Johnson Marty , Cornelison Jered , Isaac Carolyn , deJong Joyce , Prahlow Joseph A.
Published: July 2018

Postmortem fingerprint collection is a routine part of many forensic death investigations. Although the production of postmortem prints is usually straight forward, several obstacles and scenarios can make the collection difficult. A common challenge occurs when finger pads are mummified. Several current techniques allow for softening and rehydration of mummified finger pads; however, despite the employment of such techniques, the production of adequate postmortem fingerprints can remain elusive. The authors present two techniques that can improve the chances of obtaining suitable fingerprints from mummified remains. The “baby powder method” involves applying a cornstarch‐based powder, such as baby powder, onto the darkened and mummified finger pads, to allow better visualization of the fingerprint detail. The “transillumination method” involves carefully dissecting away the tissues underlying the finger pad, followed by placement of a bright light source underneath the finger pad, such that the finger ridge pattern is illuminated.
Female mice exhibit both sexual and social partner preferences for vocalizing males
Authors: NOMOTO Kensaku , IKUMI Mayu , OTSUKA Monami , ASABA Akari , KATO Masahiro , KOSHIDA Nobuyoshi , MOGI Kazutaka , KIKUSUI Takefumi
Published: July 2018

Acoustic signals are widely used as courtship signals in the animal kingdom. It has long been known that male mice emit ultrasonic vocalizations (USVs) in the presence of female mice or in response to female secretions. This observation led to the hypothesis that male USVs play a role in courtship behavior. Although previous studies showed that female mice have a social partner preference for vocalizing males, it is not known if they exhibit a sexual partner preference when given a choice. To address this issue, we examined the copulatory behaviors of female mice with either devocalized males (with or without the playback of the USVs) or sham‐operated males in 2 different behavioral paradigms: the no‐choice paradigm in the home cage of a male mouse (without choice of mating partners) or the mate‐choice paradigm in a 3‐chambered apparatus (with choice of mating partners). In the no‐choice paradigm, female mice exhibited comparable sexual receptivity with sham‐operated and devocalized males. In addition, we found that female mice showed more approach behavior towards devocalized males when male USVs were played back. In the mate‐choice paradigm, female mice visited more frequently and stayed longer with sham‐operated than devocalized males. Furthermore, we showed that female mice received more intromissions from sham‐operated males than devocalized males. In summary, our results suggested that, although female mice can copulate equally with both devocalized and vocalizing males when given no choice of mating partner, female mice exhibit both sexual and social partner preferences for vocalizing males in the mate‐choice paradigm.