bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study
Authors: Schrepf Andrew , Harper Daniel E. , Harte Steven E. , Wang Heng , Ichesco Eric , Hampson Johnson P. , Zubieta Jon-Kar , Clauw Daniel J. , Harris Richard E.
Published: June 2016

Endogenous opioid system dysfunction potentially contributes to chronic pain in fibromyalgia (FM), but it is unknown if this dysfunction is related to established neurobiological markers of hyperalgesia. We previously reported that µ-opioid receptor (MOR) availability was reduced in patients with FM as compared with healthy controls in several pain-processing brain regions. In the present study, we compared pain-evoked functional magnetic resonance imaging with endogenous MOR binding and clinical pain ratings in female opioid-naive patients with FM (n = 18) using whole-brain analyses and regions of interest from our previous research. Within antinociceptive brain regions, including the dorsolateral prefrontal cortex (r = 0.81, P < 0.001) and multiple regions of the anterior cingulate cortex (all r > 0.67; all P < 0.02), reduced MOR availability was associated with decreased pain-evoked neural activity. Additionally, reduced MOR availability was associated with lower brain activation in the nucleus accumbens (r = 0.47, P = 0.050). In many of these regions, pain-evoked activity and MOR binding potential were also associated with lower clinical affective pain ratings. These findings are the first to link endogenous opioid system tone to regional pain-evoked brain activity in a clinical pain population. Our data suggest that dysregulation of the endogenous opioid system in FM could lead to less excitation in antinociceptive brain regions by incoming noxious stimulation, resulting in the hyperalgesia and allodynia commonly observed in this population. We propose a conceptual model of affective pain dysregulation in FM.
Donor Oversizing Results in Improved Survival in Patients with Left Ventricular Assist Device
Authors: Schumer Erin M. , Black Matthew C. , Rogers Michael P. , Trivedi Jaimin R. , Birks Emma J. , Lenneman Andrew J. , Cheng Allen , Slaughter Mark S.
Published: June 2016

Donor to recipient undersizing can result in diminished graft survival. The United Network for Organ Sharing database was retrospectively queried from January 2008 to December 2013 to identify adult patients who underwent heart transplantation. This population was divided into those without and with a left ventricular assist device (LVAD) at the time of transplant. Both groups were further subdivided into three groups: donor:recipient body mass index (BMI) ratio <0.8 (undersized), ≥0.8 and ≤1.2 (matched), and >1.2 (oversized). Kaplan–Meier analysis was used to compare graft survival. Cox regression analysis was used to identify factors affecting graft survival time. There was no difference in mean graft survival between undersized, matched, and oversized groups in patients without an LVAD (p = 0.634). Mean graft survival was significantly worse for undersized patients with an LVAD when compared with matched and oversized patients (p = 0.032). Cox regression revealed age, creatinine, waitlist time, United Network for Organ Sharing status, BMI ratio, and total bilirubin as significant factors affecting graft survival time. A donor to recipient BMI ratio of ≥1.2 results in significantly improved long-term graft survival for patients with an LVAD at the time of heart transplantation compared with patients with a BMI ratio of <1.2. An oversized organ should be considered for patients supported with an LVAD.
A Case Series of Acute Myocardial Infarction in Left Ventricular Assist Device-Supported Patients
Authors: Godishala Anuradha , Nassif Michael E. , Raymer David S. , Hartupee Justin , Ewald Gregory A. , Larue Shane J. , Vader Justin M.
Published: June 2016

Acute myocardial infarction (AMI) is an underrecognized phenomenon in patients with continuous-flow left ventricular assist devices (CF-LVAD). Previously, there has been an optimistic expectation of a benign clinical course; however, AMI in LVAD-supported patients can result in profound consequences and management remains controversial. We describe a case series of AMI in four CF-LVAD patients, each with a different presentation, clinical course, treatment, and outcome. The clinical variability and mixed outcomes of these patients highlights the unique challenges in diagnosis and management of AMI in this population, particularly the uncertain role of percutaneous intervention (PCI), and underscores the potentially poor prognosis of this entity. Several key points emerge from this review. First, LVAD-supported patients frequently have underlying abnormalities on the electrocardiogram (ECG) that obscure the diagnosis of AMI. Second, clinicians should have a high degree of suspicion for AMI in the presence of suggestive clinical features, elevated cardiac biomarkers, or new-onset ventricular arrhythmias. Third, the decision to proceed with PCI requires careful evaluation of the risk of hemorrhage, and strong consideration should be given to the use of bleeding avoidance strategies during and after PCI.
Postoperative bleeding and coagulation disorders
Authors: Samama Charles Marc
Published: June 2016

Purpose of review

New data have been made available in the field of haemostasis and thrombosis. Some long-awaited answers to important questions have been published, and some debates have benefited from an updated perspective.

Recent findings

Two important domains are addressed in this update: massive bleeding (1/1/1 ratios and fibrinogen concentrates) and the management of direct oral anticoagulants (monitoring and antidotes). Both are highly controversial topics. Higher plasma/platelets/red blood cells units ratios are now partly supported by a new study in trauma. Several studies show that preemptive doses of fibrinogen do not appear to bring any benefit. Monitoring of direct oral anticoagulants is now possible, and it has to be recommended in some circumstances. Specific antidotes are being developed, but there are still more questions than answers.

These new data should help anaesthesiologists and intensivists to better understand and manage massively bleeding patients or direct oral anticoagulants treated patients.
Bedside nutrition evaluation and physical assessment techniques in critical illness
Authors: Simpson Fiona , Doig Gordon S.
Published: June 2016

Purpose of review

The purpose of this review is to highlight emerging techniques used to determine body composition early in ICU stay, their prediction of poor outcome, and what is required before they can be more widely used.

Recent findings

Opportunistic use of imaging techniques to assess muscle mass shows promise with regard to predicting patient outcomes; however, some of these techniques are expensive. Mid-arm muscle circumference and physical assessments of muscle wasting and subcutaneous fat loss using the subjective global assessment (SGA) are simple cheap tools that can be undertaken at the ICU patient bedside. Furthermore, each of these simple measures is a better predictor of patient outcome than BMI.

Mid-arm muscle circumference, SGA fat loss, and SGA muscle wasting have each been found to be better predictors of poor outcome than BMI in ICU patients.

Mid-arm muscle circumference, SGA fat loss, and SGA muscle wasting may be able to identify patients who are most likely to benefit from enhanced nutrition support.

We need further research incorporating the use of these simple measures to evaluate their ability to accurately identify patients most likely to benefit from enhanced nutritional support.
Protein delivery in critical illness
Authors: Weijs Peter J.M.
Published: June 2016

Purpose of review

Protein delivery in the critically ill still is a highly debated issue. Here, we discuss only the most recent updates in the literature concerning protein nutrition of the critically ill.

Recent findings

Up to now, there are no randomized controlled trials (RCTs) published on enteral provision of protein that were randomized for protein level of intake. In the past year, there have been two new observational studies published, one of which in critically ill children. Also, two randomized controlled trials with high parenteral amino acid provision have been published. The overall view on nutrition support has not been changed convincingly by these studies. Recent findings have confirmed that protein and amino acid provision are highly important for outcome in critically ill patients. For the first time, a randomized study confirmed this, however, only on the short term. The other RCT confirmed that an extreme dosing of amino acids is not related to improvement in outcome. One observational study showed that the effect of protein on outcome should be adjusted for energy intake and vice versa, showing that adequate protein is related to improved outcome and adequate energy provision is not. The other observational study confirmed importance of protein in paediatric ICU but also gained some insight into improvement of protein delivery by postpyloric feeding and usefulness of a dedicated dietitian in the ICU.

We will continue to improve protein delivery to critically ill patients; however, the quest for evidence and feeding guidelines still remains.
Nucleic acid biomarkers of β cell stress and death in type 1 diabetes
Authors: Syed Farooq , Evans-Molina Carmella
Published: June 2016

Purpose of review

The purpose of this review is to summarize recent advances in the development of nucleic acid-based biomarkers of type 1 diabetes (T1D).

Recent findings

Recent rodent and human studies have identified new roles for stress pathways intrinsic to the β cell during the development of T1D. As such, methods to identify an authentic nucleic acid signature of β cell stress and/or death may improve our ability to predict T1D at earlier timepoints, allowing for optimal timing of immunomodulatory interventions. To this end, both targeted and unbiased approaches have begun to identify changes in microRNA expression patterns in T1D. Moreover, a number of groups have developed distinct assays that quantitatively detect circulating unmethylated insulin DNA, which is thought to primarily emanate from dying β cells.

Here we highlight unique blood and urine microRNA signatures identified in T1D cohorts, compare differences between first, second, and third-generation assays that detect circulating unmethylated insulin DNA, and review recent technological advances that have the capacity to improve T1D biomarker development.
Type B insulin resistance syndrome
Authors: Willard Devina L. , Stevenson Mary , Steenkamp Devin
Published: June 2016

Purpose of review

To review the epidemiology, pathophysiology, clinical features, and management of type B insulin resistance syndrome.

Recent findings

Type B insulin resistance syndrome is a rare disorder caused by autoantibodies to the insulin receptor. This disorder is most frequently reported in middle-aged black women and is invariably associated with other autoimmune diseases. Typically, refractory transient hyperglycemia and extreme insulin resistance are the cardinal features, but hypoglycemia may also occur. Traditionally, the high reported mortality rate was typically attributed to the hypoglycemia. There is no well standardized treatment regimen. However, recent therapeutic advances with combination immunomodulatory therapy have led to significant reported improvements in hypoglycemia-associated mortality and durability of remission.

We review the literature on the pathophysiology and clinical features of type B insulin resistance syndrome and highlight the complexities and recent advances in the management of this disorder.
Pituitary diseases and sleep disorders
Authors: Romijn Johannes A.
Published: June 2016

Purpose of review

Patients with pituitary diseases have decreased quality of life. Sleep disorders are prevalent among patients with pituitary diseases and contribute to decreased quality of life.

Recent findings

Patients previously treated for compression of the optic chiasm by surgery, and in some cases postoperative radiotherapy, suffer from sleep disorders. These are characterized by decreased sleep quality, delayed onset of sleep, and daytime sleepiness. Circumstantial evidence suggests that this may be caused by hypothalamic dysfunction. A challenging speculation is that previous compression of the optic chiasm compromised the function of the retinohypothalamic tract. Through this tract the eyes convey information on day–night cycles to the hypothalamic nuclei. Patients with acromegaly, even despite biochemical control, suffer frequently from obstructive sleep apnea. Patients with Cushing's disease suffer from fragmented sleep, sleep apnea, and snoring. Prolactinomas do not seem to affect sleep characteristics. The association between appropriately substituted pituitary insufficiency and sleep disorders is less clear. The effects of recombinant human growth hormone on sleep characteristics in adults are inconsistent.

Pituitary disorders are associated with different sleep disorders. Different studies point to irreversible changes in sleep–wake rhythmicity in patients treated previously for pituitary tumors with chiasm compression.

Video abstract

http://links.lww.com/COE/A12
Autoimmune hepatitis and long-term disease course in children in Turkey, a single-center experience
Authors: Karakoyun Miray , Ecevit Cigdem O. , Kilicoglu Erhan , Aydogdu Sema , Yagci Rasit V. , Ozgenc Funda
Published: June 2016

Introduction

The aim of this study is to determine clinic and laboratory features, treatment protocols, treatment responses, and long term follow-up of children with autoimmune hepatitis (AIH) in a region of Turkey followed at Ege University.

Materials and methods

The records of 47 children with AIH between 1998 and 2012 were retrospectively analyzed for clinical profiles, treatment response, relapse rate, and long-term side effects.

Results

The median age of the children was 10±4.1 years (55.3% females). A total of 29 patients presented with chronic hepatitis (61.7%). According to the autoantibody profiles, 40 (85.1%) and seven (14.9%) cases were classified as type 1 and type 2, respectively. Presentation with acute hepatitis and chronic hepatitis was significantly higher in type 1 disease. Laboratory findings at presentation was found similar among races as well as AIH types (P>0.05). The prednisolone was used for remission induction in 37 patients; 86.4% (n: 32) achieved a complete response, 2.7% (n: 1) achieved a partial response, and four patients (10.8%) showed no response. Maintenance was attained by low-dose steroid plus thiopurine and relapse in steroid responders (n: 32) was 9.4% (n: 3) at 8, 12, and 48 months. A total of 36% (n: 24) had neither acute nor chronic treatment side effects. Bone marrow suppression was observed in five patients and hyperglycemia was observed in one patient (10.6 and 2.1%), respectively.

Conclusion

AIH type 1 prevails in children in a region of Turkey during the second decade of life. Low-dose corticosteroids combined with azathioprine are found.
Safety of Bifidobacterium animalis Subsp. Lactis (B. lactis) Strain BB‐12‐Supplemented Yogurt in Healthy Children
Authors: Tan Tina P. , Ba Zhaoyong , Sanders Mary E. , D'Amico Frank J. , Roberts Robert F. , Smith Keisha H. , Merenstein Daniel J.
Published: June 2016

Objectives:

Probiotics are live microorganisms that may provide health benefits to the individual when consumed in sufficient quantities. For studies conducted on health or disease endpoints on probiotics in the United States, the Food and Administration has required those studies to be conducted as investigational new drugs. This phase I, double‐blinded, randomized, controlled safety study represents the first requirement of this pathway. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp. lactis (B lactis) strain BB‐12 (BB‐12)‐supplemented yogurt when consumed by a generally healthy group of children. The secondary aim was to assess the effect of BB‐12‐supplemented yogurt on the gut microbiota of the children.

Methods:

Sixty children ages 1 to 5 years were randomly assigned to consume 4 ounces of either BB‐12‐supplemented yogurt or nonsupplemented control yogurt daily for 10 days. The primary outcome was to assess safety and tolerability, as determined by the number of reported adverse events.

Results:

A total of 186 nonserious adverse events were reported, with no significant differences between the control and BB‐12 groups. No significant changes due to probiotic treatment were observed in the gut microbiota of the study cohort.

Conclusions:

BB‐12‐supplemented yogurt is safe and well‐tolerated when consumed by healthy children. The present study will form the basis for future randomized clinical trials investigating the potential effects of BB‐12‐supplemented yogurt in different disease states.
Assessment of the Family History of Patients With Ulcerative Colitis at a Single Center in Japan
Authors: Fujii Tohru , Sato Masamichi , Hosoi Kenji , Ohbayashi Naho , Ikuse Tamaki , Jimbo Keisuke , Aoyagi Yo , Kudo Takahiro , Ohtsuka Yoshikazu , Shimizu Toshiaki
Published: June 2016

Objectives:

The prevalence of ulcerative colitis (UC) differs by country, which is likely due to differences in genetic factors among ethnicities. Moreover, the prevalence of pediatric UC with a family history (FH) is 4.1% in Japanese patients; its clinical course begins at an early age and is more severe. Recently, a genome‐wide association study identified 3 new susceptibility loci for adult Japanese patients with UC.

Methods:

To assess the effects of FH in patients with UC, 60 children were enrolled. Age at diagnosis, clinical features of the initial symptoms, and family structure were assessed in patients with and without an FH. The 3 new loci were examined in patients who provided informed consent.

Results:

Of the patients with UC, 10 (16.7%) had an FH involving first‐degree relatives, including 7 mothers, 1 father, and 2 sisters. There was a trend toward a younger age at onset in the positive FH group. There were, however, no significant differences in the clinical characteristics of the patients regardless of FH. From the genomic analyses, there were significant differences in the polymorphisms of the solute carrier family 26, member 3 (SLC26A3) between those with and without an FH.

Conclusions:

Although the etiology of UC remains unknown, there were no observed relation between clinical symptoms and FH. SLC26A3 may, however, contribute to the pathogenesis of UC in Japanese individuals with an FH.
Childhood Rhabdomyosarcoma in Association With a RASopathy Clinical Phenotype and Mosaic Germline SOS1 Duplication
Authors: Salem Baheyeldin , Hofherr Sean , Turner Joyce , Doros Leslie , Smpokou Patroula
Published: June 2016

Childhood rhabdomyosarcoma (RMS) accounts for approximately 3.5% of cancer cases among children 0 to 14 years of age. Genetic conditions associated with high risk of childhood RMS include Li-Fraumeni syndrome, pleuropulmonary blastoma, Beckwith-Wiedemann syndrome, and some RASopathies, such as neurofibromatosis type 1, Costello syndrome (CS), and Noonan syndrome (NS). Here, we report the rare case of a 4-year-old girl with clinical features of NS who developed an embryonal RMS of the chest and needed emergent treatment. Molecular genetic testing identified a de novo, large, mosaic duplication of chromosome 2 encompassing theSOS1gene, presumably caused by a mosaic, unbalanced translocation between chromosomes 2 and 17 found on routine cytogenetic analysis. Sequence analysis of all known genes causing Noonan spectrum disorders was negative. RMS has been reported in a few patients with NS, associated in very few with germlineSOS1mutations, but none with copy number abnormalities. This is the first report to our knowledge of early-onset RMS developing in a child with features of NS and a mosaic RAS pathway gene aberration, a largeSOS1duplication. We hypothesize that the inciting event for tumor development in this case is due to the germline mosaic duplication ofSOS1, which was duplicated in all cells of the tumor, and the ultimate development of the tumor was further driven by multiple chromosomal aberrations in the tumor itself, all described as somatic events in isolated RMS tumors.
American Psychiatric Nurses Association—Transitions in Practice Certificate Program
Authors: Adams Susie M. , Black Patricia
Published: June 2016

The purpose of this article is to publicize an important new Web-based educational program. Recognizing the growing gap in psychiatric-mental health knowledge and the need to better prepare new graduates and nurses transitioning from other service lines into psychiatric inpatient nursing settings, the American Psychiatric Nurses Association developed a 15-hour, modularized curriculum to provide foundational psychiatric-mental health knowledge. This modularized curriculum, called American Psychiatric Nurses Association Transitions in Practice (ATP) focuses on the knowledge and skills to insure the success of nurses new to psychiatric-mental health nursing settings and to improve the overall care for persons with mental health and substance use disorders. The ATP program is also proving to be useful content for nurses in emergency departments, hospitals, and other health settings to improve their care of patients with psychiatric and mental health needs. A summary of the program modules and a toolkit with suggested measures for nurses, patients, and agency outcomes is described. Feedback from participants completing the ATP program within the first 6 months is overwhelmingly positive and holds promise for widespread application across a variety of health care settings.
Pilot Study of Parent Psychophysiologic Outcomes in Pediatric Hematopoietic Stem Cell Transplantation
Authors: Ward Jessica , Swanson Barbara , Fogg Louis , Rodgers Cheryl
Published: June 2016

Background:

Parents of children undergoing hematopoietic stem cell transplantation (HSCT) are at risk for psychological distress. This distress may result in aberrant immune, inflammatory, or endocrine effects. These physiologic outcomes have not been reported previously.

Main Objective:

The aim of this study is to examine the feasibility of longitudinal testing of psychophysiological parameters of stress in parents of children undergoing HSCT.

Methods:

This pilot study was conducted at a large children’s hospital in the Midwest and included parents of children who received autologous or allogeneic HSCT. Time points included before the start of HSCT conditioning and day +30, +60, and +100. Outcome variables included parent-perceived stress, lymphocyte subsets, C-reactive protein (CRP), proinflammatory cytokines, salivary cortisol, and salivary amylase. Effect sizes were calculated for each outcome.

Results:

Twelve parent-child dyads were enrolled (10 mothers, 2 fathers). Missing data were minimal. Parent-perceived stress significantly increased from pre-HSCT through day +100, and parent CD3+ T-lymphocyte counts decreased from pre-HSCT through day +100. No significant effects were observed for salivary studies, CRP, or proinflammatory cytokines. Effect sizes ranged from 1.23 (perceived stress) to 0.07 (CRP).

Conclusion:

The results of this study suggest that it is feasible longitudinally measure parent psychophysiologic outcomes in the pediatric HSCT setting. In addition, parent-perceived stress increased linearly from start of conditioning through day +100, whereas parent T-lymphocyte counts decreased concurrently.

Implications for Practice:

Routine psychological and physical health screening of parents of children undergoing HSCT is needed. Multidisciplinary psychosocial support services should be offered to parents at regular intervals during their child’s HSCT.
Coriander: Overview of Potential Health Benefits
Authors: Singletary Keith
Published: June 2016

Coriander (Coriandrum sativum L.) is a spice obtained from the plant belonging to the family Umbelliferae (Apiaceae). The green, young coriander leaves, also known as cilantro, and the aromatic coriander fruit or seed find uses in curry meat dishes, poultry and seafood dishes, a variety of ethnic foods, puddings, breads, soups, and stews. In traditional remedies, coriander was used for relief of gastrointestinal maladies, although other historical uses included as an aphrodisiac, antibiotic, a remedy for respiratory ailments and pain, and a treatment for loss of appetite and memory. Current uses being investigated include its antioxidant, antimicrobial, diabetes-modulating, and neurological benefits.
Dual-Polymer Drops, Contact Lens Comfort, and Lid Wiper Epitheliopathy
Authors: Nichols Jason J. , Lievens Christopher W. , Bloomenstein Marc R. , Liu Haixia , Simmons Peter , Vehige Joseph
Published: June 2016

Purpose

This study compared a new contact lens rewetting drop containing both carboxymethylcellulose and hyaluronic acid (CMC-HA) with a standard drop containing carboxymethylcellulose only (CMC). Symptoms of discomfort typical in lens wear and lid wiper epitheliopathy (LWE) were assessed over a 3-month period in a diverse sample of contact lens wearers.

Methods

Adapted daily-wear contact lens subjects using hydrogel, silicone hydrogel, or rigid gas permeable lenses were enrolled in this prospective, randomized, double-masked, parallel-group, 90-day study conducted at 15 clinical sites. Subjects were randomized 2:1 to CMC-HA (n = 244) or CMC alone (n = 121) with dosage at least four times per day, along with their habitual lens care system. At baseline and at days 7, 30, 60, and 90, subject-completed questionnaires, bulbar conjunctival staining, LWE, contact lens distance visual acuity (CLDVA), and standard safety measures were assessed.

Results

At day 90, CMC-HA performed significantly better than CMC in ocular symptoms including dryness throughout the day (p = 0.006), and burning/stinging throughout the day (p = 0.02) and at the end of the day (p < 0.001). CMC-HA also performed numerically better for dryness at the end of day (p = 0.06). LWE staining was improved in the CMC-HA group at day 90 whereas it increased slightly in the CMC alone group, with a significant between-group difference (p = 0.009). CMC-HA also demonstrated greater reduction in conjunctival staining compared with CMC alone at day 90 (p = 0.08). No differences in CLDVA, contact lens wear time, acceptability, and product use were observed, and safety outcomes were similar between groups.

Conclusions

The addition of HA to a standard CMC rewetting drop improves clinical performance. In this comparison of rewetting drop efficacy in contact lens wearers, LWE was a useful clinical sign for differentiating clinical performance.
Demographic Factors Affect Ocular Comfort Ratings During Contact Lens Wear
Authors: Naduvilath Thomas , Papas Eric B. , Lazon de la Jara Percy
Published: June 2016

Purpose

To determine if rating of ocular comfort during soft contact lens wear is affected by demographic factors.

Methods

Retrospective analysis of ocular comfort ratings during soft contact lens wear extracted from 44 nonrandomized similar clinical trials (n = 986). Subjects wore one of seven daily wear silicone hydrogels (SiHy) in combination with one of nine lens care products (LCP), and two daily disposables lenses. The effects on comfort rating of demographic factors were examined after adjusting for lens and LCP effects using general linear model.

Results

Males reported lower comfort on insertion than females (7.9 ± 1.6 vs. 8.1 ± 1.6, p = 0.001). Over 45 years old had higher comfort ratings than those between 26 and 45 or <26 years old at insertion (8.7 ± 1.3 vs. 8.1 ± 1.6 vs. 7.8 ± 1.6, p < 0.001), during the day (8.6 ± 1.2 vs. 8.0 ± 1.6 vs. 8.2 ± 1.2, p < 0.001), and end of day (7.7 ± 1.6 vs. 6.8 ± 2.0 vs. 7.0 ± 1.6, p < 0.001). Neophytes reported lower comfort on insertion (7.3 ± 1.6 vs. 8.2 ± 1.5, p < 0.001) and during day (8.0 ± 1.3 vs. 8.3 ± 1.3, p = 0.020) than experienced wearers. Participants with Rx ≥−3.50D had higher comfort ratings than those with ≤−3.50D on insertion (8.3 ± 1.4 vs. 7.8 ± 1.6, p < 0.001), during the day (8.4 ± 1.3 vs. 8.1 ± 1.3, p = 0.010), and end of day (7.2 ± 1.7 vs. 6.9 ± 1.8, p = 0.046). Comfort during the day was different between participants of different ethnic origin (p = 0.024) with Asians reporting the lowest (8.1 ± 1.3).

Conclusions

Demographic factors such as age, gender, lens wear experience, ethnicity, and refractive status can influence the rating of ocular comfort in clinical studies. The confounding effects of such demographic factors can be controlled by implementing randomization and appropriate multivariable statistical analysis.
Distinctive Patterns of CTNNB1 (β-Catenin) Alterations in Salivary Gland Basal Cell Adenoma and Basal Cell Adenocarcinoma
Authors: Jo Vickie Y. , Sholl Lynette M. , Krane Jeffrey F.
Published: June 2016

Salivary gland basaloid neoplasms are diagnostically challenging. Limited publications report that some basal cell adenomas harborCTNNB1mutations, and nuclear β-catenin expression is prevalent. We evaluated β-catenin expression in basal cell adenomas and adenocarcinomas in comparison with salivary tumors in the differential diagnosis and performed targeted genetic analysis on a subset of cases. β-catenin immunohistochemistry was performed on formalin-fixed, paraffin-embedded whole sections from 73 tumors. Nuclear staining was scored semiquantitatively by extent and intensity. DNA was extracted from 6 formalin-fixed, paraffin-embedded samples (5 basal cell adenomas, 1 basal cell adenocarcinoma) for next-generation sequencing. Nuclear β-catenin staining was present in 18/22 (82%) basal cell adenomas; most were diffuse and strong and predominant in the basal component. Two of 3 basal cell adenocarcinomas were positive (1 moderate focal; 1 moderate multifocal). All adenoid cystic carcinomas (0/20) and pleomorphic adenomas (0/20) were negative; 2/8 epithelial-myoepithelial carcinomas showed focal nuclear staining. Most β-catenin-negative tumors showed diffuse membranous staining in the absence of nuclear staining. Four of 5 basal cell adenomas had exon 3CTNNB1mutations, all c.104T>C (p.I35T). Basal cell adenocarcinoma showed a more complex genomic profile, with activating mutations inPIK3CA, biallelic inactivation ofNFKBIA, focalCYLDdeletion, and withoutCTNNB1mutation despite focal β-catenin expression. Nuclear β-catenin expression has moderate sensitivity (82%) for basal cell adenoma but high specificity (96%) in comparison with its morphologic mimics.CTNNB1mutation was confirmed in most basal cell adenomas tested, and findings in basal cell adenocarcinoma suggest possible tumorigenic mechanisms, including alterations in PI3K and NF-κB pathways and transcriptional regulation.
Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors
Authors: Agaram Narasimhan P. , Zhang Lei , Sung Yun-Shao , Chen Chun-Liang , Chung Catherine T. , Antonescu Cristina R. , Fletcher Christopher DM
Published: June 2016

The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft tissue tumors resembling LPF, but displaying cytologic atypia and a neural immunophenotype, provisionally named LPF-like neural tumors.
Outcomes After Pediatric Out-of-Hospital Cardiopulmonary Interventions
Authors: Lo Jennifer Y. , Tani Lloyd Y. , Christensen Miles , Sheng Xiaoming , Clawson Jason , Menon Shaji C.
Published: June 2016

Objective

The aim of the study was to evaluate outcomes after pediatric out-of-hospital cardiopulmonary interventions (CPIs) by emergency medical services (EMS).

Methods

Children (age, ≤18 years) who received CPI by EMS from 2001 to 2008 were identified from the Utah Department of Health. Cardiopulmonary intervention was defined as oxygenation, ventilation or CPR, and transport to a hospital by EMS. Univariate and multivariable regression analyses evaluated associations between potential predictors and outcomes (death and new neurologic dysfunction).

Results

A total of 464 patients (58% male) received EMS attention. For the 71% patients (327) who were alive on EMS arrival, 63% (205) received CPI without CPR. Of note, 6% (12) of these patients died after arrival to the hospital and new neurologic dysfunction was diagnosed in 6% (13). Among the 12 patients who died, 50% (6) were younger than 1 year.

On multivariable regression analysis, factors associated with increased risk of death before and in-hospital are the following: age younger than 1 year (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.17–0.39), shorter EMS transport time (OR, 0.94; 95% CI, 0.89–0.99), and longer EMS dispatch time (OR, 1.23; 95% CI, 1.08–1.40). Factors associated with increased risk of new neurologic dysfunction are the following: lack of pulse (OR, 0.14; 95% CI, 0.04–0.53), requiring CPR (OR, 6.15; 95% CI, 1.48–25.6), and CPR duration (OR, 1.20; 95% CI, 1.05–1.37).

Conclusions

Age younger than 1 year, shorter transport time, and longer dispatch time were associated with increased risk of death. Being pulseless upon discovery and receiving CPR were associated with new neurologic dysfunction. Maximizing EMS transport interventions for patients younger than 1 year requiring CPI may improve patient outcomes.
Acute Disseminated Encephalomyelitis
Authors: Gray Matthew Philip , Gorelick Marc H.
Published: June 2016

Acute disseminated encephalomyelitis is a primarily pediatric, immune-mediated disease characterized by demyelination and polyfocal neurologic symptoms that typically occur after a preceding viral infection or recent immunization. This article presents the pathophysiology, diagnostic criteria, and magnetic resonance imaging characteristics of acute disseminated encephalomyelitis. We also present evaluation and management strategies.
Brief Report: HIV-1 Infection Impairs CD16 and CD35 Mediated Opsonophagocytosis of Mycobacterium tuberculosis by Human Neutrophils
Authors: Bangani Nonzwakazi , Nakiwala Justine , Martineau Adrian R. , Wilkinson Robert J. , Wilkinson Katalin A. , Lowe David M.
Published: June 2016

Using a flow cytometric assay, we investigated neutrophil–Mycobacterium tuberculosis opsonophagocytosis and the impact of HIV-1–infected serum on this process. The mean (±SD) percentage of neutrophils internalizing bacilli after 30 minutes incubation was significantly reduced by pretreatment with anti-CD16 (18.2% ± 8.1%, P < 0.001) or anti-CD35 antibody (23.2% ± 10.6%, P < 0.05) versus anti-CD4 controls (29.9% ± 8.1%). Blocking CD88 or CD11a did not affect internalization. Using heat-inactivated serum, maximal internalization was lower using HIV-1–infected serum versus HIV-1–uninfected. Using non–heat-inactivated serum, internalization decreased more rapidly with sequential dilutions of HIV-1–infected versus HIV-1–uninfected serum. CD16 and CD35 are important for neutrophil internalization of M. tuberculosis, whereas HIV-1 infection adversely affects opsonophagocytosis.
More Than One Way to Debrief
Authors: Sawyer Taylor , Eppich Walter , Brett-Fleegler Marisa , Grant Vincent , Cheng Adam
Published: June 2016

Summary Statement

Debriefing is a critical component in the process of learning through healthcare simulation. This critical review examines the timing, facilitation, conversational structures, and process elements used in healthcare simulation debriefing. Debriefing occurs either after (postevent) or during (within-event) the simulation. The debriefing conversation can be guided by either a facilitator (facilitator-guided) or the simulation participants themselves (self-guided). Postevent facilitator-guided debriefing may incorporate several conversational structures. These conversational structures break the debriefing discussion into a series of 3 or more phases to help organize the debriefing and ensure the conversation proceeds in an orderly manner. Debriefing process elements are an array of techniques to optimize reflective experience and maximize the impact of debriefing. These are divided here into the following 3 categories: essential elements, conversational techniques/educational strategies, and debriefing adjuncts. This review provides both novice and advanced simulation educators with an overview of various methods of conducting healthcare simulation debriefing. Future research will investigate which debriefing methods are best for which contexts and for whom, and also explore how lessons from simulation debriefing translate to debriefing in clinical practice.
Recent advances in genetics of chorea
Authors: Mencacci Niccolò E. , Carecchio Miryam
Published: June 2016

Purpose of review

Chorea presenting in childhood and adulthood encompasses several neurological disorders, both degenerative and nonprogressive, often with a genetic basis. In this review, we discuss how modern genomic technologies are expanding our knowledge of monogenic choreic syndromes and advancing our insight into the molecular mechanisms responsible for chorea.

Recent findings

A genome-wide association study in Huntington's disease identified genetic disease modifiers involved in controlling DNA repair mechanisms and stability of the HTT trinucleotide repeat expansion. Chorea is the cardinal feature of newly recognized genetic entities, ADCY5 and PDE10A-related choreas, with onset in infancy and childhood. A phenotypic overlap between chorea, ataxia, epilepsy, and neurodevelopmental disorders is becoming increasingly evident.

The differential diagnosis of genetic conditions presenting with chorea has considerably widened, permitting a molecular diagnosis and an improved prognostic definition in an expanding number of cases. The identification of Huntington's disease genetic modifiers and new chorea-causing gene mutations has allowed the initial recognition of converging molecular pathways underlying medium spiny neurons degeneration and dysregulation of normal development and activity of basal ganglia circuits. Signalling downstream of dopamine receptors and control of cAMP levels represent a very promising target for the development of new aetiology-based treatments for chorea and other hyperkinetic disorders.
Bounds on the power of proofs and advice in general physical theories
Authors: Lee Ciarán M. , Hoban Matty J.
Published: June 2016

Quantum theory presents us with the tools for computational and communication advantages over classical theory. One approach to uncovering the source of these advantages is to determine how computation and communication power vary as quantum theory is replaced by other operationally defined theories from a broad framework of such theories. Such investigations may reveal some of the key physical features required for powerful computation and communication. In this paper, we investigate how simple physical principles bound the power of two different computational paradigms which combine computation and communication in a non-trivial fashion: computation with advice and interactive proof systems. We show that the existence of non-trivial dynamics in a theory implies a bound on the power of computation with advice. Moreover, we provide an explicit example of a theory with no non-trivial dynamics in which the power of computation with advice is unbounded. Finally, we show that the power of simple interactive proof systems in theories where local measurements suffice for tomography is non-trivially bounded. This result provides a proof thatQMAis contained inPP, which does not make use of any uniquely quantum structure—such as the fact that observables correspond to self-adjoint operators—and thus may be of independent interest.
Fibre break failure processes in unidirectional composites: evaluation of critical damage states
Authors: Thionnet A. , Bunsell A. R.
Published: May 2016

Earlier work which successfully modelled the kinetics of fibre breakage in unidirectional composites under monotonic tensile loading has been extended to quantify the kinetics of fibre failure during both monotonic and sustained tensile loading. In both cases, failure was seen to occur when a critical density of large clusters (more than 16 fibres are broken within the representative volume element) of fibre breaks developed. However, in monotonic loading failure occurred very quickly after the first development of these large clusters, whereas under sustained loading the composite could accommodate greater levels of large clusters because of the lower applied load.

This article is part of the themed issue ‘Multiscale modelling of the structural integrity of composite materials’.
Environmental degradation of composites for marine structures: new materials and new applications
Authors: Davies Peter
Published: May 2016

This paper describes the influence of seawater ageing on composites used in a range of marine structures, from boats to tidal turbines. Accounting for environmental degradation is an essential element in the multi-scale modelling of composite materials but it requires reliable test data input. The traditional approach to account for ageing effects, based on testing samples after immersion for different periods, is evolving towards coupled studies involving strong interactions between water diffusion and mechanical loading. These can provide a more realistic estimation of long-term behaviour but still require some form of acceleration if useful data, for 20 year lifetimes or more, are to be obtained in a reasonable time. In order to validate extrapolations from short to long times, it is essential to understand the degradation mechanisms, so both physico-chemical and mechanical test data are required. Examples of results from some current studies on more environmentally friendly materials including bio-sourced composites will be described first. Then a case study for renewable marine energy applications will be discussed. In both cases, studies were performed first on coupons at the material level, then during structural testing and analysis of large components, in order to evaluate their long-term behaviour.

This article is part of the themed issue ‘Multiscale modelling of the structural integrity of composite materials’.
Prediction of failure in notched carbon-fibre-reinforced-polymer laminates under multi-axial loading
Authors: Tan J. L. Y. , Deshpande V. S. , Fleck N. A.
Published: May 2016

A damage-based finite-element model is used to predict the fracture behaviour of centre-notched quasi-isotropic carbon-fibre-reinforced-polymer laminates under multi-axial loading. Damage within each ply is associated with fibre tension, fibre compression, matrix tension and matrix compression. Inter-ply delamination is modelled by cohesive interfaces using a traction-separation law. Failure envelopes for a notch and a circular hole are predicted for in-plane multi-axial loading and are in good agreement with the observed failure envelopes from a parallel experimental study. The ply-by-ply (and inter-ply) damage evolution and the critical mechanisms of ultimate failure also agree with the observed damage evolution. It is demonstrated that accurate predictions of notched compressive strength are obtained upon employing the band broadening stress for microbuckling, highlighting the importance of this damage mode in compression.

This article is part of the themed issue ‘Multiscale modelling of the structural integrity of composite materials’.
From matrix nano- and micro-phase tougheners to composite macro-properties
Authors: Kinloch A. J. , Taylor A. C. , Techapaitoon M. , Teo W. S. , Sprenger S.
Published: May 2016

In this paper, firstly, the morphology and toughness of a range of bulk epoxy polymers, which incorporate a second phase of well-dispersed silica nanoparticles and/or rubber microparticles, have been determined. Secondly, the macro-properties of natural-fibre reinforced-plastic (NFRP) composites based upon these epoxy polymers have been ascertained, using (i) unidirectional flax fibres or (ii) regenerated-cellulose fibres in the architecture of a plain-woven fabric. Thirdly, the toughening mechanisms which are induced in these materials by the presence of the silica nanoparticles, the rubber microparticles and the natural fibres have been identified. Finally, the values of the toughness of the bulk epoxy polymers and corresponding NFRPs have been quantitatively modelled. The increased toughness recorded for the bulk epoxy polymer due to the presence of the silica nanoparticles and/or rubber microparticles was indeed typically transferred to the NFRP composites when using such epoxies as the matrices for the fibres. Thus, the important role that may be played by modifications to the epoxy matrices in order to increase the toughness of the composites was very clearly demonstrated by these results. However, notwithstanding, the toughening mechanisms induced by the fibres were essentially responsible for the very high toughnesses of the NFRP composites, compared with the bulk epoxy polymers. The modelling studies successfully predicted the values of toughness of the bulk epoxy polymers and of the NFRP composites. These studies also quantified the extent to which each toughening mechanism, induced by the second-phase nano- and microparticles and the natural fibres, contributed to the overall values of toughness of the materials.

This article is part of the themed issue ‘Multiscale modelling of the structural integrity of composite materials’.