bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II
Authors: Tumlin James A. , Murugan Raghavan , Deane Adam M. , Ostermann Marlies , Busse Laurence W. , Ham Kealy R. , Kashani Kianoush , Szerlip Harold M. , Prowle John R. , Bihorac Azra , Finkel Kevin W. , Zarbock Alexander , Forni Lui G. , Lynch Shannan J. , Jensen Jeff , Kroll Stew , Chawla Lakhmir S. , Tidmarsh George F. , Bellomo Rinaldo
Published: March 2018

Objective:

Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy.

Design:

Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial.

Setting:

ICUs.

Patients:

Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively).

Interventions:

IV angiotensin II or placebo.

Measurements and Main Results:

Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%–67%) and 30% (95% CI, 19%–41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%–54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%–27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%–68%) and 22% (95% CI, 12%–34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively.

Conclusions:

In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.
Systematic Review of Standardized Patient Use in Continuing Medical Education
Authors: Wilbur Kerry , Elmubark Alaa , Shabana Sara
Published: March 2018

Introduction:

The standardized patient (SP) has assumed a fundamental role in undergraduate medical education since first conceived over 50 years ago. While widely used in student training and assessment of communication and clinical examination across health disciplines, little is known how SPs enhance knowledge or skill development among professionals. We conducted a systematic review to determine the effectiveness of SPs in continuing medical education (CME) programs.

Methods:

Authors independently searched for studies published between 1966 and 2016, describing CME initiatives using SP encounters as practice for participants compared with those which did not. Studies assessing virtual patients or mannequins or employing SPs for assessment only were excluded. Learning outcomes were characterized according to the Kirkpatrick framework for determining the effectiveness of training programs.

Results:

Four hundred eighty-eight studies were identified, but only five were eligible for analysis. Most were conducted with small numbers of primary care physicians in North America. CME topics related to opioid prescribing, breast cancer examination and cancer screening, smoking cessation, and chronic asthma management. In the two studies testing knowledge, no difference was found between intervention and control groups (Kirkpatrick level 2). Improved behaviors were demonstrated in breast cancer patient examination and interview and decreased opioid-prescribing rates among selected participants in two studies (Kirkpatrick level 3). Only one study investigated patient outcomes and found reduced rates of uncontrolled asthma in practices of physicians who were assigned to SP practice encounters in the CME training (Kirkpatrick level 4).

Discussion:

There is little rigorous outcome study of CME programs incorporating SPs. Given the necessary human and fiscal resources associated with their use, our review highlights the need to reconsider the SP role in CME unless further purposeful evaluation to determine participant behavior change and related patient outcomes is pursued.
Assessment of Interprofessional Team Collaboration Scale (AITCS): Further Testing and Instrument Revision
Authors: Orchard Carole , Pederson Linda L. , Read Emily , Mahler Cornelia , Laschinger Heather
Published: March 2018

Introduction:

The need to be able to assess collaborative practice in health care teams has been recognized in response to the direction for team-based care in a number of policy documents. The purpose of this study is to report on further refinement of such a measurement instrument, the Assessment of Interprofessional Team Collaboration Scale (AITCS) first published in 2012. To support this refinement, two objectives were set: Objective 1: to determine whether the items from the data collected in 2016 load on the same factors as found for the 2012 version of the 37-item AITCS. Objective 2: to determine whether the items in the subscales of the AITCS could be reduced while retaining psychometric properties similar to those from the earlier versions of the AITCS.

Methods:

Initially, the overall data sets of 1002 respondents from two hospitals and four community agencies were analyzed for demographics and scale and subscale mean values, SDs, and mean item scores. After deletion of respondents because of missing data, 967 respondents were available for the first analysis. An exploratory factor analysis was then conducted to determine the factor structure. All respondents with any random missing data were further removed to reduce the data set to 676 responses, followed by a confirmatory factor analysis to find a model fit resulting in an item reduction in the scale.

Results:

The result was a 23-item AITCS-II for practitioners that retained acceptable levels of reliability and validity within 3 subscales—partnership (8 items), cooperation (8 items), and coordination (7 items).

Discussion:

The shortened version of the AITCS-II is a valid and reliable instrument that can be used to assess collaboration in health care teams in practice settings.
Applications of Computer Technology in Complex Craniofacial Reconstruction
Authors: Day Kristopher M. , Gabrick Kyle S. , Sargent Larry A.
Published: March 2018

Background:

To demonstrate our use of advanced 3-dimensional (3D) computer technology in the analysis, virtual surgical planning (VSP), 3D modeling (3DM), and treatment of complex congenital and acquired craniofacial deformities.

Methods:

We present a series of craniofacial defects treated at a tertiary craniofacial referral center utilizing state-of-the-art 3D computer technology. All patients treated at our center using computer-assisted VSP, prefabricated custom-designed 3DMs, and/or 3D printed custom implants (3DPCI) in the reconstruction of craniofacial defects were included in this analysis.

Results:

We describe the use of 3D computer technology to precisely analyze, plan, and reconstruct 31 craniofacial deformities/syndromes caused by: Pierre-Robin (7), Treacher Collins (5), Apert’s (2), Pfeiffer (2), Crouzon (1) Syndromes, craniosynostosis (6), hemifacial microsomia (2), micrognathia (2), multiple facial clefts (1), and trauma (3). In select cases where the available bone was insufficient for skeletal reconstruction, 3DPCIs were fabricated using 3D printing. We used VSP in 30, 3DMs in all 31, distraction osteogenesis in 16, and 3DPCIs in 13 cases. Utilizing these technologies, the above complex craniofacial defects were corrected without significant complications and with excellent aesthetic results.

Conclusion:

Modern 3D technology allows the surgeon to better analyze complex craniofacial deformities, precisely plan surgical correction with computer simulation of results, customize osteotomies, plan distractions, and print 3DPCI, as needed. The use of advanced 3D computer technology can be applied safely and potentially improve aesthetic and functional outcomes after complex craniofacial reconstruction. These techniques warrant further study and may be reproducible in various centers of care.
Living High and Feeling Low: Altitude, Suicide, and Depression
Authors: Kious Brent M. , Kondo Douglas G. , Renshaw Perry F.
Published: March 2018

Learning objectives

After participating in this activity, learners should be better able to:

• Assess epidemiologic evidence that increased altitude of residence is linked to increased risk of depression and suicide

• Evaluate strategies to address hypoxia-related depression and suicidal ideation

Suicide and major depressive disorder (MDD) are complex conditions that almost certainly arise from the influences of many interrelated factors. There are significant regional variations in the rates of MDD and suicide in the United States, suggesting that sociodemographic and environmental conditions contribute. Here, we review epidemiological evidence that increases in the altitude of residence are linked to the increased risk of depression and suicide. We consider the possibility that chronic hypobaric hypoxia (low blood oxygen related to low atmospheric pressure) contributes to suicide and depression, which is suggested by animal models, short-term studies in humans, and the effects of hypoxic medical conditions on suicide and depression. We argue that hypobaric hypoxia could promote suicide and depression by altering serotonin metabolism and brain bioenergetics; both of these pathways are implicated in depression, and both are affected by hypoxia. Finally, we briefly examine treatment strategies to address hypoxia-related depression and suicidal ideation that are suggested by these findings, including creatine monohydrate and the serotonin precursors tryptophan and 5-hydroxytryptophan.
Relationships Between Subcortical Shape Measures and Subjective Symptom Reporting in US Service Members With Mild Traumatic Brain Injury
Authors: Bolzenius Jacob D. , Wade Benjamin S. C. , Velez Carmen S. , Drennon Ann Marie , Cooper Douglas B. , Kennedy Jan E. , Reid Matthew W. , Bowles Amy O. , Thompson Paul M. , Gutman Boris , Lewis Jeffrey D. , Ritter John L. , York Gerald E. , Bigler Erin D. , Tate David F.
Published: March 2018

Objective:

To assess interactions of subcortical structure with subjective symptom reporting associated with mild traumatic brain injury (mTBI), using advanced shape analysis derived from volumetric MRI.

Participants:

Seventy-six cognitively symptomatic individuals with mTBI and 59 service members sustaining only orthopedic injury.

Design:

Descriptive cross-sectional study.

Main Measures:

Self-report symptom measures included the PTSD Checklist-Military, Neurobehavioral Symptom Inventory, and Symptom Checklist-90-Revised. High-dimensional measures of shape characteristics were generated from volumetric MRI for 7 subcortical structures in addition to standard volume measures.

Results:

Several significant interactions between group status and symptom measures were observed across the various shape measures. These interactions were revealed in the right thalamus and globus pallidus for each of the shape measures, indicating differences in structure thickness and expansion/contraction for these regions. No relationships with volume were observed.

Conclusion:

Results provide evidence for the sensitivity of shape measures in differentiating symptomatic mTBI individuals from controls, while volumetric measures did not exhibit this same sensitivity. Disruptions to thalamic nuclei identified here highlight the role of the thalamus in the spectrum of symptoms associated with mTBI. Additional work is needed to prospectively, and longitudinally, assess these measures along with cognitive performance and advanced multimodal imaging methods to extend the utility of shape analysis in relation to functional outcomes in this population.
Should Routine Postoperative Clinic Visits Be Phased Out?
Authors: Litz Cristen N. , McGuire Margaret , Danielson Paul D. , Chandler Nicole M.
Published: March 2018

Introduction

Postoperative clinic visits are often considered routine practice in pediatric surgery. The purpose of this study was to determine family preferences regarding routine clinic visits among those presenting for postoperative visits.

Methods

Patients aged 18–21 years or the parents/guardians of patients aged 0–17 years who underwent appendectomy, pyloromyotomy, umbilical/inguinal hernia repair, circumcision, or supernumerary digit removal between November 18, 2015, and October 28, 2016, were approached at the postoperative visit to complete a survey.

Results

The survey was completed by 151 participants. Clinic visits were preferred by 66% of respondents, and this did not differ by age, educational level, urgency of operation, work/school missed, or frequency of email use. Respondents with concerns that were addressed were more likely to prefer in-office follow-up (79%) compared with those whose concerns were not addressed (44%) or those without concerns (37%; p ≤ .01). There was a trend toward preference for in-office follow-up from respondents who traveled less than 15 minutes (<15 vs. 16–30 vs. >30 minutes: 81% vs. 60% vs. 62%, respectively; p = .09) and those evaluated by surgeons (surgeon vs. advanced practice provider: 71% vs. 58%, respectively; p = .06). Additional interventions were performed in eight patients (5%).

Discussion

Most families who present for postoperative clinic visits prefer follow-up in clinic despite the resources required to attend the visit.
Inflammatory Cytokine Profile in Crohn’s Disease Nonresponders to Optimal Antitumor Necrosis Factor Therapy
Authors: Yarur Andres J. , Jain Anjali , Quintero Maria A. , Czul Frank , Deshpande Amar R. , Kerman David H. , Abreu Maria T.
Published: March 2018

Background:

A significant number of patients receiving therapy with antitumor necrosis factor (TNF) agents for Crohn’s disease experience primary or secondary nonresponse. The aim of this study was to assess whether patients with nonresponse to anti-TNF agents have increased expression of alternative cytokine pathways.

Methods:

We designed a prospective, cross-sectional study that included patients with Crohn’s disease receiving anti-TNF undergoing colonoscopy with adequate serum trough drug levels (≥8 µg/mL) and without anti-drug antibodies. Inflammatory cytokines and cell adhesions markers measured included intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, interleukin (IL)-8, IL-1β, and IL-6. The primary outcome was the presence of active endoscopic inflammation defined as the presence of at least 1 ulceration ≥5 mm.

Results:

In total, 47 patients were included. Patients with active inflammation had significantly higher levels of ICAM-1 and IL-1β when compared with those without intestinal inflammation (45.9 vs. 35.8 ng/mL, P<0.0001 and 3.2 vs. 1.5 pg/mL, P=0.002, respectively). There were no significant differences in the other study variables. Using receiving operating curves, ICAM and IL-1β had a good correlation (receiver operating characteristic ≥0.8) with inflammation in this cohort of patients with “anti-TNF resistance.” The results were similar in the group of patients with previous anti-TNF exposure.

Conclusion:

Our study suggests that patients who have active inflammation with seemingly adequate serum anti-TNF levels have increased levels of specific inflammatory pathways that may serve as biomarkers of nonresponse as well as potential targets of therapy in anti-TNF nonresponders.
Esophageal Food Impaction
Authors: Melendez-Rosado Jose , Corral Juan E. , Patel Sheetal , Badillo Raul J. , Francis Dawn
Published: March 2018

Goals:

The goal of this study is to examine the causes, type of adverse events (AE), and effects of elective intubation in outcomes associated with esophageal food impaction (EFI).

Background:

EFI is a gastrointestinal emergency requiring immediate medical attention.

Study:

Retrospective review of all EFI cases presenting at 3 large tertiary centers from October 1, 2011 to October 31, 2014 and all cases registered in the Clinical Outcome Research Initiative (CORI) database from January 1, 2000 to December 31, 2012. Statistical analysis compared health care utilization, AEs, and outcomes in patients with or without elective intubation.

Results:

A total of 214 cases presenting with EFI at our 3 referral hospitals and 4950 cases in the CORI database met inclusion criteria. Prevalence of structural disorders was similar in the Mayo Clinic and CORI datasets: 24.3% and 27.7% had strictures, and 3.8% and 2.5% had a tumor, respectively. AEs in the nonintubation group were 14.7% compared with 33.3% in the elective intubation group (P=0.003); however, 71.0% of these events were associated with EFI itself and not therapeutic procedure. Esophageal AEs were common (15.0%), followed by pulmonary and cardiovascular events with 3.0% and 1.4%, respectively. Severity of the AEs was influenced by the impaction-to-endoscopy time.

Conclusions:

Prevalence of structural esophageal disorders was similar to previous smaller studies. Elective intubation was associated with increased AEs; however, this is felt to be because of the nature of EFI itself and not by therapeutic endoscopy. Prolonged impaction-to-endoscopy time was associated with severe AEs.
The institutional development award states pediatric clinical trials network: building research capacity among the rural and medically underserved
Authors: Snowden Jessica , Darden Paul , Palumbo Paul , Saul Phil , Lee Jeannette
Published: March 2018

Purpose of review

The institutional development award (IDeA) program was created to increase the competitiveness of investigators in states with historically low success rates for National Institutes of Health (NIH) research funding applications. IDeA states have high numbers of rural and medically underserved residents with disproportionately high rates of infant mortality, obesity, and poverty. This program supports the development and expansion of research infrastructure and research activities in these states. The IDeA States Pediatric Clinical Trials Network (ISPCTN) is part of the environmental influences on child health outcomes program. Its purpose is to build research capacity within IDeA states and provide opportunities for children in IDeA states to participate in clinical trials. This review describes the current and future activities of the network.

Recent findings

In its initial year, the ISPCTN created an online series on clinical trials, initiated participation in a study conducted by the pediatric trials network, and proposed two novel clinical trials for obese children. Capacity building and clinical trial implementation will continue in future years.

The ISPCTN is uniquely poised to establish and support new pediatric clinical research programs in underserved populations, producing both short and long-term gains in the understanding of child health.
TH1 and TH2 Cytokine Profiles as Predictors of Severity in Acute Pancreatitis
Authors: Rodriguez-Nicolas Antonio , Martínez-Chamorro Alba , Jiménez Pilar , Matas-Cobos Ana M. , Redondo-Cerezo Eduardo , Ruiz-Cabello Francisco
Published: March 2018

Objectives

Acute pancreatitis (AP) is severe in up to 20% of patients, with a high mortality rate. Quantification of serum TH1 and TH2 cytokines may provide objective evidence to assess the severity of AP and predict its course.

Methods

One hundred seventeen patients were studied, measuring serum concentrations of interleukin (IL)1β, IL2, IL4, IL5, IL6, IL10, IL12p70, IL13, IL18, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN) γ, and tumor necrosis factor (TNF) α.

Results

Significant differences were found between patients with severe AP and those with mild or moderately severe AP in IFN-γ (P < 0.001), IL6 (P < 0.001), TNF-α (P = 0.002), GM-CSF (P < 0.001), IL4 (P = 0.002), IL1b (P = 0.017), and IL13 (P < 0.001) concentrations. Interferon-γ, IL6, and TNF-α were associated with severe AP, whereas GM-CSF, IL4, IL1b, and IL13 were associated with mild or moderately severe AP. The IL13/IFNγ ratio was significantly higher in patients with mild AP (P = 7.36 × 10−8).

Conclusions

A TH1 profile was associated with severe AP and a TH2 profile with mild or moderately severe AP. We report an IL13/IFNγ ratio of potential value to predict the prognosis in AP.
Weekend Effect in Acute Pancreatitis–Related Hospital Admissions in the United States
Authors: Sharma Prabin , Aguilar Rodrigo , Nader Mark Abi , Siddiqui Shaheryar , Baniya Ramkaji , Bhandari Sanjeeb Sudarshan , Cervantes Carmen Elena , Correa Ricardo , Masoud Amir
Published: March 2018

Objective

This study aimed to assess the difference in overall outcomes between weekend admissions for acute pancreatitis (AP) and weekday admissions.

Methods

Between 2005 and 2012, data were extracted from the Nationwide Inpatient Sample on adult patients with AP. Exclusion criteria were applied for chronic pancreatitis and other pancreatic and biliary malignancies. In-hospital mortality, length of stay, hospitalization costs, comorbidities, complications, and intervention rates were compared between the weekend and weekday admissions.

Results

During the study period, there were a total of 432,303 weekday admissions and 147,435 weekend admissions for AP in the United States hospitals. Weekend AP admissions were more likely to develop alcohol withdrawal (5.9% vs 5.7%, P = 0.001) and ileus (4.1% vs 3.1%, P = 0.04). They were also more likely to develop acute respiratory distress syndrome (4.7% vs 4.4%, P < 0.001) and required more endotracheal intubation (3.9% vs 3.6%, P < 0.001). There was no significant in-hospital mortality difference between the weekend and weekday admissions on both univariate and multivariate analysis.

Conclusions

Weekend AP admissions develop more severe complications requiring intensive care. Despite this, there was no weekend effect for in-hospital mortality for AP-related admissions.
Establishment and Verification of a Scoring Model for the Differential Diagnosis of Pancreatic Cancer and Chronic Pancreatitis
Authors: Zhang Huimin , Han Wei , Jin Meng , Lai Yamin , Wang Xi , Wang Jian , Yao Yao , Wu Dong , Qian Jiaming , Yang Hong
Published: March 2018

Objectives

The aims of this study were to establish a scoring model for the differential diagnosis of pancreatic cancer (PC) and chronic pancreatitis (CP) and to evaluate its diagnostic efficacy.

Methods

The data of 502 patients with PC and 210 patients with CP at the Peking Union Medical College Hospital from January 1999 to December 2013 were retrospectively analyzed. Binary logistic regression was applied to establish the prediction model for the differential diagnosis. The model was verified using the method of leave-one-out cross-validation.

Results

The scoring system was established with 5 variables including age, carbohydrate antigen 19-9 level, splenic vein invasion, irregular dilatation of the pancreatic duct, and nontruncated pancreatic duct stenosis. The score range was from −2 to 3. The area under the receiver operating characteristic curve of the objects was 0.779 (95% confidence interval, 0.744–0.814) (P < 0.01), indicating that the scoring system is good at differentiation of PC with CP. With a score of 1 as the diagnostic cut-off value, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate were 71.3%, 69.0%, 70.0%, 71.4%, and 70.2%, respectively.

Conclusions

The scoring model may improve the differential diagnosis of PC and CP and be useful in clinical practice.
Immunohistochemical Detection of γ/δ T Lymphocytes in Formalin-fixed Paraffin-embedded Tissues
Authors: Jungbluth Achim A. , Frosina Denise , Fayad Miriam , Pulitzer Melissa P. , Dogan Ahmet , Busam Klaus J. , Imai Naoko , Gnjatic Sacha
Published: March 2018

T lymphocytes can be distinguished based on the composition of the T-cell receptor (TCR) chain in α/β T cells and γ/δ T cells. Correspondingly, α/β lymphomas can be distinguished from γ/δ lymphomas. The latter are rare neoplasms, which are usually confined to particular organs and tissues and carry a dismal prognosis. Until recently, monoclonal antibody (mAb) clone g3.20 to the TCR γ-chain was the reagent of choice for the immunohistochemical detection of γ/δ T cells and lymphomas in standard formalin-fixed paraffin-embedded tissues. However, due to technical problems, mAb g3.20 became recently unavailable. Our attempts to identify another commercially available clone to the TCR γ-chain were unsuccessful. However, we were able to identify a mAb (clone H-41, SC-100289; Santa Cruz, Dallas, TX) to the TCR δ-chain. H-41 works well in immunohistochemistry on paraffin-embedded tissue and comparison with previously stained cases, shows superior immunolabeling to mAb g3.20. H-41 to the TCR δ-chain appears to be a suitable reagent for the replacement of mAb g3.20.
From acute to persistent low back pain: a longitudinal investigation of somatosensory changes using quantitative sensory testing—an exploratory study
Authors: Marcuzzi Anna , Wrigley Paul J. , Dean Catherine M. , Graham Petra L. , Hush Julia M.
Published: March 2018

Introduction:

Chronic low back pain (LBP) is commonly associated with generalised pain hypersensitivity. It is suggested that such somatosensory alterations are important determinants for the transition to persistent pain from an acute episode of LBP. Although cross-sectional research investigating somatosensory function in the acute stage is developing, no longitudinal studies designed to evaluate temporal changes have been published.

Objectives:

This exploratory study aimed to investigate the temporal development of somatosensory changes from the acute stage of LBP to up to 4 months from onset.

Methods:

Twenty-five people with acute LBP (<3 weeks' duration) and 48 pain-free controls were prospectively assessed at baseline using quantitative sensory testing with the assessor blinded to group allocation, and again at 2 and 4 months. Psychological variables were concurrently assessed. People with acute LBP were classified based on their average pain severity over the previous week at 4 months as recovered (≤1/10 numeric rating scale) or persistent (≥2/10 numeric rating scale) LBP.

Results:

In the persistent LBP group, (1) there was a significant decrease in pressure pain threshold between 2 and 4 months (P < 0.013), and at 4 months, pressure pain threshold was significantly different from the recovered LBP group (P < 0.001); (2) a trend towards increased temporal summation was found at 2 months and 4 months, at which point it exceeded 2 SDs beyond the pain-free control reference value. Pain-related psychological variables were significantly higher in those with persistent LBP compared with the recovered LBP group at all time points (P < 0.05).

Conclusion:

Changes in mechanical pain sensitivity occurring in the subacute stage warrant further longitudinal evaluation to better understand the role of somatosensory changes in the development of persistent LBP. Pain-related cognitions at baseline distinguished persistent from the recovered LBP groups, emphasizing the importance of concurrent evaluation of psychological contributors in acute LBP.
Supporting Our Team Through Creating Awareness
Authors: Kasales Claudia , Wall Darci , Harer Nora , Goss Sheryl
Published: March 2018

Musculoskeletal injuries have been and remain a significant issue for sonographers. Despite its importance, the topic of musculoskeletal injury in sonographers has received little attention in the radiology literature. Our goal is to bring this extremely important issue to the forefront, with the hope of initiating conversations and actions leading to improved workplace practices for sonographers.
Serous Cystic Neoplasms of the Pancreas
Authors: Hwang Hyeonseung , Yu Jeong-Sik , Cho Eun-Suk , Kim Joo Hee , Chung Jae-Joon
Published: March 2018

Our purpose was to assess the endoscopic ultrasonography (EUS) features of serous cystic neoplasms (SCNs) of the pancreas in determining the surgical removal compared with computed tomography (CT) and magnetic resonance imaging (MRI) features. For 33 consecutive patients with 34 surgically confirmed SCNs over the past 11 years, preoperative EUS features were compared with those of CT and MRI (CT&MRI). Besides the lesion size and location, a retrospective analysis of the various imaging features was performed by 2 observers to understand the characteristics that determine the need for surgical intervention in terms of multiplicity of locules, calcification, mural thickening, mural nodules, ductal communication, and main pancreatic duct dilatation in addition to the gross morphologic type: microcystic, macrocystic (>1 cm), mixed, or solid. The most common gross morphologic type was mixed lesions, which consisted of microcystic and macrocystic components (15/34; 44%), followed by microcystic (38%), macrocystic (15%), and solid (3%) lesions. A minority (5/34; 18%) of the lesions showed main pancreatic duct dilatation (upstream, n = 3; downstream, n = 0; diffuse, n = 2). Mural nodules or solid components were more frequently noted in EUS (67%) than in CT&MRI (25%; P = 0.001), whereas other findings showed no remarkable difference between EUS and CT&MRI (P > 0.05). In determining the surgical treatment of multiloculated cystic lesions, interpretation of EUS features for the presence of solid component or mural nodules should be more carefully determined, especially in the patients with suggestive features of SCN on CT or MRI to avoid unnecessary surgery.
Stability of combustion waves in a simplified gas–solid combustion model in porous media
Authors: Ozbag Fatih , Schecter Stephen
Published: March 2018

We study the stability of the combustion waves that occur in a simplified model for injection of air into a porous medium that initially contains some solid fuel. We determine the essential spectrum of the linearized system at a travelling wave. For certain waves, we are able to use a weight function to stabilize the essential spectrum. We perform a numerical computation of the Evans function to show that some of these waves have no unstable discrete spectrum. The system is partly parabolic, so the linearized operator is not sectorial, and the weight function decays at one end. We use an extension of a recent result about partly parabolic systems that are stabilized by such weight functions to show nonlinear stability.

This article is part of the theme issue ‘Stability of nonlinear waves and patterns and related topics’.
Periodic waves of the Lugiato–Lefever equation at the onset of Turing instability
Authors: Delcey Lucie , Haragus Mariana
Published: March 2018

We study the existence and the stability of periodic steady waves for a nonlinear model, the Lugiato–Lefever equation, arising in optics. Starting from a detailed description of the stability properties of constant solutions, we then focus on the periodic steady waves which bifurcate at the onset of Turing instability. Using a centre manifold reduction, we analyse these Turing bifurcations, and prove the existence of periodic steady waves. This approach also allows us to conclude on the nonlinear orbital stability of these waves for co-periodic perturbations, i.e. for periodic perturbations which have the same period as the wave. This stability result is completed by a spectral stability result for general bounded perturbations. In particular, this spectral analysis shows that instabilities are always due to co-periodic perturbations.

This article is part of the theme issue ‘Stability of nonlinear waves and patterns and related topics’.
Wavenumber selection via spatial parameter jump
Authors: Scheel Arnd , Weinburd Jasper
Published: March 2018

The Swift–Hohenberg equation describes an instability which forms finite-wavenumber patterns near onset. We study this equation posed with a spatial inhomogeneity; a jump-type parameter that renders the zero solution stable for
x
<0 and unstable for
x
>0. Using normal forms and spatial dynamics, we prove the existence of a family of steady-state solutions that represent a transition in space from a homogeneous state to a striped pattern state. The wavenumbers of these stripes are contained in a narrow band whose width grows linearly with the size of the jump. This represents a severe restriction from the usual constant-parameter case, where the allowed band grows with the square root of the parameter. We corroborate our predictions using numerical continuation and illustrate implications on stability of growing patterns in direct simulations.

This article is part of the theme issue ‘Stability of nonlinear waves and patterns and related topics’.
Selective activation of alternative MYC core promoters by Wnt-responsive enhancers
Authors: Bardales Jorge A. , Wieser Evin , Kawaji Hideya , Murakawa Yasuhiro , Darzacq Xavier
Published: March 2018

In Metazoans, transcription of most genes is driven through the use of multiple alternative promoters. Although the precise spatio-temporal regulation of alternative promoters is important for proper gene expression, the mechanism that mediates their differential utilization remains unclear. Here, we investigate how the two alternative promoters (P1, P2) that drive MYC expression are regulated. We find that P1 and P2 can be differentially regulated across cell-types, and that their selective usage is largely mediated by distal regulatory sequences. Moreover, we show that in the colon carcinoma cell line HCT-116, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using both transgenic reporter assays and in the context of the endogenous Myc locus upon Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by distinct core promoter elements present in the two MYC promoters. Taken together, our results provide new insights into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more diverse combinatorial regulation of transcription initiation.
Scalable approximate Bayesian inference for particle tracking data
Authors: Sun Ruoxi , Paninski Liam
Published: March 2018

Many important datasets in physics, chemistry, and biology consist of noisy sequences of images of multiple moving overlapping particles. In many cases, the observed particles are indistinguishable, leading to unavoidable uncertainty about nearby particles’ identities. Exact Bayesian inference is intractable in this setting, and previous approximate Bayesian methods scale poorly. Non-Bayesian approaches that output a single “best” estimate of the particle tracks (thus discarding important uncertainty information) are therefore dominant in practice. Here we propose a flexible and scalable amortized approach for Bayesian inference on this task. We introduce a novel neural network method to approximate the (intractable) filter-backward-sample-forward algorithm for Bayesian inference in this setting. By varying the simulated training data for the network, we can perform inference on a wide variety of data types. This approach is therefore highly flexible and improves on the state of the art in terms of accuracy; provides uncertainty estimates about the particle locations and identities; and has a test run-time that scales linearly as a function of the data length and number of particles, thus enabling Bayesian inference in arbitrarily large particle tracking datasets.
ALDH1-positive intratumoral stromal cells indicate epithelial differentiation and good prognosis in prostate cancer
Authors: Nastały Paulina , Filipska Martyna , Morrissey Colm , Eltze Elke , Semjonow Axel , Brandt Burkhard , Pantel Klaus , Bednarz-Knoll Natalia
Published: March 2018

Aldehyde dehydrogenase 1 (ALDH1) characterizes tumor-initiating cells in solid tumors, however little is known about its expression in intratumoral stromal cells. Herein, we aimed to dissect its potential dual relevance in prostate cancer (PCa).

ALDH1 expression was evaluated immunohistochemically in tumor and stromal cells in primary PCa and metastasis. It was correlated with clinico-pathological parameters, outcome of patients, and selected protein expression (CK5/6, CK14, CK8/18, CK19, EpCAM, Ki-67, E-cadherin, N-cadherin, and vimentin).

ALDH1 protein was detected in tumor and stromal cells in 16% and 67% of 348 primary PCa, respectively. Tumor cell ALDH1 expression was associated with advanced tumor (T) status (p=0.009), higher Gleason score (p=0.016), shorter time to biochemical recurrence (BR) (p=0.010) and CK14 expression (p=0.023). Stromal cell ALDH1 expression correlated with lower T status (p=0.008), N0 status (p=0.017), lower Gleason score (p=0.016) and longer time to BR (p=0.017). In the subgroup of d’Amico high-risk patients it occurred even to be an independent predictor of good prognosis (multivariate analysis, p=0.050). ALDH1 was found in stroma of tumors characterized by CK8/18 (p=0.033) or EpCAM expression (p<0.001) and rarely by epithelial-mesenchymal transition defined as CK8/18(-)vimentin(+) phenotype (p=0.003). ALDH1 was detected in tumor cells and stroma of 33% and 41% of hormone naive lymph node metastases (n=63), 52% and 24% of castration resistant bone metastases, as well as 89% and 28% of castration resistant visceral metastases (n=21), respectively.

We have determined that contrary to tumor cell ALDH1, the presence of stromal ALDH1 is associated with a more differentiated tumor epithelial phenotype in primary PCa, improved clinical outcome, and is less frequent in PCa metastases.

Abbreviations

ALDH1

aldehyde dehydrogenase 1

BR

biochemical recurrence

CK

cytokeratin

CRPC

castration resistant prostate cancer

CSC

cancer stem cell

FFPE

formalin fixed paraffin embedded tissue

IHC

immunohistochemistry

LNM

lymph node metastasis

OS

overall survival

PSA

prostate specific antigen

PT

primary tumor

REMARK

REporting recommendations for tumour MARKer prognostic studies

TMA

tissue microarray
HIV-1 Nefs are cargo-sensitive AP-1 trimerization switches in tetherin and MHC-I downregulation
Authors: Morris Kyle L. , Buffalo Cosmo Z. , Stürzel Christina M. , Heusinger Elena , Kirchhoff Frank , Ren Xuefeng , Hurley James H.
Published: March 2018

The HIV accessory protein Nef counteracts immune defenses by subverting coated vesicle pathways. The 3.7 Å cryo-EM structure of a closed trimer of the clathrin adaptor AP-1, the small GTPase Arf1, HIV-1 Nef, and the cytosolic tail of the restriction factor tetherin suggested a mechanism for inactivating tetherin by Golgi retention. The 4.3 Å structure of a mutant Nef-induced dimer of AP-1 showed how the closed trimer is regulated by the dileucine loop of Nef. HDX-MS and mutational analysis were used to show how cargo dynamics leads to alternative Arf1 trimerization, directing Nef targets to be either retained at the trans-Golgi or sorted to lysosomes. Phosphorylation of the NL4-3 M-Nef was shown to regulate AP-1 trimerization, explaining how O-Nefs lacking this phosphosite counteract tetherin but most M-Nefs do not. These observations show how the higher-order organization of a vesicular coat can be allosterically modulated to direct cargoes to distinct fates.
A reproductive arrest program triggered by defects in Piwi and germ granules
Authors: Spichal Maya , Heestand Bree , Billmyre Katherine Kretovich , Frenk Stephen , Ahmed Shawn
Published: March 2018

In several species, Piwi/piRNA genome silencing defects lead to immediate sterility accompanied by heterochromatin dysfunction and transposon-induced genomic instability, which may cause Piwi mutant sterility. InC. elegans,Piwi pathway mutants transmit a heritable stress through germ cells that induces sterility after growth for several generations. We found that sterile Piwi pathway mutant germ cells displayed inconsistent increases in DNA damage but consistently altered perinuclear germ granules that are known to promote fertility. Germ granule dysfunction did not elicit transposon expression but was sufficient to induce multiple phenotypes found in sterile Piwi silencing mutants, including germline atrophy and regrowth. Furthermore, loss of the germ granule component PGL-1 accelerated sterility in response to deficiency forprg-1/Piwi. Restoration of germ granule function to sterilepgl-1mutants restored their fertility. Together, our results suggest that germ granule defects may promote an adult reproductive arrest phenotype that is responsible for Piwi/piRNA mutant sterility.
The symbiotic complex of Dendroctonus simplex: implications in the beetle attack and its life cycle
Authors: Durand Audrey-Anne , Constant Philippe , Déziel Eric , Guertin Claude
Published: March 2018

The eastern larch beetle (Dendroctonus simplex Le Conte) is recognized as a serious destructive forest pest in the upper part of North America. Under epidemic conditions, this beetle can attack healthy trees, causing severe damages to larch stands. Dendroctonus species are considered as holobionts, as they engage in multipartite interactions with microorganisms, such as bacteria, filamentous fungi, and yeasts, which are implicated in physiological processes of the insect, such as nutrition. They also play a key role in the beetle’s attack, as they are responsible for the detoxification of the subcortical environment and weaken the tree’s defense mechanisms. The eastern larch beetle is associated with bacteria and fungi, but their implication in the success of the beetle remains unknown. Here, we investigated the bacterial and fungal microbiota of this beetle pest throughout its ontogeny (pioneer adults, larvae and pupae) by high-throughput sequencing. A successional microbial assemblage was identified throughout the beetle developmental stages, reflecting the beetle’s requirements. These results indicate that a symbiotic association between the eastern larch beetle and some of these microorganisms takes place and that this D. simplex symbiotic complex is helping the insect to colonize its host tree and survive the conditions encountered.
Chaos Game Representation: An Alignment-Free Technique for Exploring Evolutionary Relationships of Protein Sequences
Authors: Bhoumik Priyasma , Hughes Austin L.
Published: March 2018

Chaos Game Representation (CGR) is an iterative mapping technique, which shows patterns in amino acids or nucleotide sequences. Here we present a method for using CGR to explore evolutionary relationships of protein sequences based on amino acid properties and illustrate the approach with complete sets of protein translations from viral genomes. In an analysis of complete polyprotein sequences from the viral family Flaviviridae, the CGR method was able to cluster members of major viral groups together, but relations within groups were not well resolved in comparison to an alignment-based phylogeny. We applied the method to members of five different families of ssRNA positive-strand viruses, and each family formed a distinct cluster. We also present a method of testing the reliability of clustering in CGR-based trees, which involves the use of multiple random starting points for the CGR process.
Mitochondria-derived vesicles deliver antimicrobial payload to control phagosomal bacteria
Authors: Abuaita Basel H. , Schultz Tracey L. , O’Riordan Mary X.
Published: March 2018

Pathogenic bacteria taken up into the macrophage phagosome are the target of many anti-microbial effector molecules. Although mitochondria-derived antimicrobial effectors such as reactive oxygen species (mROS) are reported to aid in bacterial killing, it is unclear how these effectors reach bacteria within the phagosomal lumen. To examine the crosstalk between mitochondria and phagosomes, we monitored the production and the spatial localization of mROS during methicillin-resistantStaphylococcus aureus(MRSA) infection. We showed here mROS, specifically hydrogen peroxide (mH2O2) can be delivered into phagosomes via infection-induced mitochondria-derived vesicles, which are generated in a Parkin-dependent manner. Accumulation of mH2O2in phagosomes required TLR signaling and the mitochondrial superoxide dismutase, Sod2, which converts superoxide into mH2O2. These data highlight a novel mechanism by which the mitochondrial redox capacity enhances macrophage antimicrobial function by delivering mitochondria-derived effector molecules into bacteria-containing phagosomes.
Crystal structure of [2,13-bis(acetamido)-5,16-dimethyl-2,6,13,17-tetraazatricyclo[16.4.0.07,12]docosane-κ4
N]silver(II) dinitrate from synchrotron X-ray data
Authors: Moon Dohyun , Choi Jong-Ha
Published: March 2018

The asymmetric unit of the title compound, [Ag(C24H46N6O2)](NO3)2 [C24H46N6O2 is (5,16-dimethyl-2,6,13,17-tetraazatricyclo[16.4.0.07,12]docosane-2,13-diyl)diacetamide, L], consists of one independent half of the [Ag(C24H46N6O2)]2+ cation and one nitrate anion. The Ag atom, lying on an inversion centre, has a square-planar geometry and the complex adopts a stable trans-III conformation. Interestingly, the two O atoms of the pendant acetamide groups are not coordinated to the AgII ion. The longer distance of 2.227 (2) Å for Ag—N(tertiary) compared to 2.134 (2) Å for Ag—N(secondary) may be due to the effects of the attached acetamide group on the tertiary N atom. Two nitrate anions are very weakly bound to the AgII ion in the axial sites and are further connected to the ligand of the cation by N—H...O hydrogen bonds. The crystal packing is stabilized by hydrogen-bonding interactions among the N—H donor groups of the macrocycle and its actetamide substituents, and the O atoms of the nitrate anions and of an acetamide group as the acceptor atoms.
Recent developments inMrBUMP: better search-model preparation, graphical interaction with search models, and solution improvement and assessment
Authors: Keegan Ronan M. , McNicholas Stuart J. , Thomas Jens M. H. , Simpkin Adam J. , Simkovic Felix , Uski Ville , Ballard Charles C. , Winn Martyn D. , Wilson Keith S. , Rigden Daniel J.
Published: March 2018

Increasing sophistication in molecular-replacement (MR) software and the rapid expansion of the PDB in recent years have allowed the technique to become the dominant method for determining the phases of a target structure in macromolecular X-ray crystallography. In addition, improvements in bioinformatic techniques for finding suitable homologous structures for use as MR search models, combined with developments in refinement and model-building techniques, have pushed the applicability of MR to lower sequence identities and made weak MR solutions more amenable to refinement and improvement.MrBUMPis aCCP4 pipeline which automates all stages of the MR procedure. Its scope covers everything from the sourcing and preparation of suitable search models right through to rebuilding of the positioned search model. Recent improvements to the pipeline include the adoption of more sensitive bioinformatic tools for sourcing search models, enhanced model-preparation techniques including better ensembling of homologues, and the use of phase improvement and model building on the resulting solution. The pipeline has also been deployed as an online service throughCCP4online, which allows its users to exploit large bioinformatic databases and coarse-grained parallelism to speed up the determination of a possible solution. Finally, the molecular-graphics applicationCCP4mghas been combined withMrBUMPto provide an interactive visual aid to the user during the process of selecting and manipulating search models for use in MR. Here, these developments inMrBUMPare described with a case study to explore how some of the enhancements to the pipeline and toCCP4mgcan help to solve a difficult case.