bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the Medial and Lateral Humeral Lines as an Adjunct to Intraoperative Elbow Arthrography to Guide Intraoperative Reduction and Fixation of Distal Humerus Physeal Separations Reduces the Incidence of Postoperative Cubitus Varus
Authors: Chou Andrew Chia Chen , Wong Ho Yin Kevin , Kumar Sumanth , Mahadev Arjandas
Published: March 2018

Background:

Distal humerus physeal separations are rare pediatric elbow fractures that are often misdiagnosed and difficult to treat. Adequate reduction is often technically challenging and up to 71% of children develop postoperative cubitus varus. We propose using the medial and lateral humeral lines as an adjunct to elbow arthrography in order to guide intraoperative fixation of distal humerus physeal separations to reduce the incidence of postoperative cubitus varus.

Methods:

From 2009 to 2014, all pediatric patients under the age of 3 diagnosed with a distal humerus physeal separation and treated surgically at our institution were included for analysis. Two senior pediatric orthopaedic surgeons separately reviewed the preoperative, intraoperative, and postoperative images of all patients and measured the position of the ulnar axis relative to the medial and lateral humeral lines. The medial and lateral humeral shafts were defined as parallel lines drawn along the medial and lateral humeral diaphysis. Adequate reduction was defined by reduction of the ulnar axis within the boundaries of the medial and lateral humeral lines. Patients were assessed at latest follow-up for cubitus varus and any other surgical complications.

Results:

Thirteen patients fulfilled the inclusion criteria and were on average 1.70 years old, ranging from 0.62 to 3 years old. Intraoperatively and immediately postoperatively, all 13 patients (100%) were noted to have adequate reduction of the ulnar axis within the boundaries medial and lateral humeral lines. None of the patients required intraoperative arthrography (0%). At the date of latest follow-up, 12 patients (92.3%) had no angular deformities compared with the contralateral limb and 1 patient (7.7%) had developed cubitus varus. No surgical complications were noted (0%).

Conclusion:

Intraoperative reduction of the ulnar axis within the boundaries of the medial and lateral humeral lines is associated with a lower incidence of postoperative cubitus varus in the treatment of distal humerus physeal separations in children.

Level of Evidence:

Level IV.
Flexion-Relaxation Phenomenon in Children and Adolescents With and Without Nonspecific Chronic Low Back Pain
Authors: Tabard-Fougère Anne , Dayer Romain , Armand Stéphane , Vuillerme Nicolas
Published: March 2018

Study Design.

A cross-sectional comparative study.

Objective.

This study aimed to investigate the flexion-relaxation phenomenon (FRP), in standing trunk flexion and slumped sitting tasks, by comparing children and adolescents suffering from nonspecific chronic low back pain (NSCLBP) with controls (CTRL).

Summary of Background Data.

The absence of the FRP can accurately discriminate adults with NSCLBP from those without during standing trunk flexion and slumped sitting tasks. Even if the FRP has been extensively studied in adults with NSCLBP, only one study has evaluated the FRP in adolescents, during a slumped sitting task, and this suggested that the FRP was also present in adolescents with NSCLBP.

Methods.

Thirty-seven children and adolescents with NSCLBP and 23 CTRL performed standing trunk flexion and slumped sitting tasks. All participants were equipped with surface electromyography (EMG) electrodes on the erector spinae longissimus (ESL) and multifidus (M) muscles and reflective markers on the spinous processes of C7, L1, and S1. Global (C7-S1), thoracic (C7-L1), and lumbar (L1-S1) trunk flexion absolute angle were measured. The FRP was reported using visual inspection and a flexion-relaxation ratio (FRR). A self-reference threshold was used to identify the time of FRP onset. Repeated-measures analysis of variance (ANOVA) was used to determine the main and interaction effects of task, group and muscle on FRR, and the relative maximal angle at FRP onset of the global trunk (C7-S1).

Results.

Results showed three main findings: (1) the FRP's low sensitivity in discriminating between NSCLBP and CTRL participants in groups, tasks, or muscles; (2) similar observed maximal flexion angles in both groups during flexion tasks; and (3) similar observed relative maximal global trunk flexion angles at FRP onset in groups, tasks, and muscles.

Conclusion.

These results are not consistent with the literature on adults and could lead to modified therapeutic management of NSCLBP in children and adolescents.

Level of Evidence: 3
Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock*
Authors: Skytte Larsson Jenny , Krumbholz Vitus , Enskog Anders , Bragadottir Gudrun , Redfors Bengt , Ricksten Sven-Erik
Published: March 2018

Objective:

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock.

Design:

Prospective comparative study.

Setting:

General and cardiothoracic ICUs.

Patients:

Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58).

Interventions:

None.

Measurements and Main Results:

Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (–24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (–21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (–19%; p = 0.068) in the septic group. Glomerular filtration rate (–32%; p = 0.006) and renal sodium reabsorption (–29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated.

Conclusions:

In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.
A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination With Ofatumumab After Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma
Authors: Robertson Michael J. , Stamatkin Christopher W. , Pelloso David , Weisenbach Jill , Prasad Nagendra K. , Safa Ahmad R.
Published: March 2018

Interleukin-18 (IL-18) is an immunostimulatory cytokine that augments antibody-dependent cellular cytotoxicity mediated by human natural killer cells against antibody-coated lymphoma cells in vitro and that has antitumor activity in animal models. Ofatumumab is a CD20 monoclonal antibody with activity against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20+ lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Cohorts of 3 patients were given intravenous infusions of ofatumumab 1000 mg weekly for 4 weeks with escalating doses of rhIL-18 as a intravenous infusion weekly for 8 consecutive weeks. Nine male patients with CD20+ lymphomas were given ofatumumab in combination with rhIL-18 at doses of 3, 10, and 30 μg/kg. No unexpected or dose-limiting toxicities were observed. The mean reduction from predose levels in the number of peripheral blood natural killer cells after the first rhIL-18 infusion was 91%, 96%, and 97% for the 3, 10, and 30 μg/kg cohorts, respectively. Serum concentrations of interferon-γ and chemokines transiently increased following IL-18 dosing. rhIL-18 can be given in biologically active doses by weekly infusions in combination with ofatumumab after peripheral blood stem cell transplantation to patients with lymphoma. A maximum tolerated dose of rhIL-18 plus ofatumumab was not determined. Further studies of rhIL-18 and CD20 monoclonal antibodies in B-cell malignancies are warranted.
Phase I/II Study of Hepatic Arterial Infusion of Nab-paclitaxel in Patients With Metastatic Melanoma to the Liver
Authors: Vera-Aguilera Jesus , Bedikian Agop Y. , Bassett Roland L. , Hwu Wen-Jen , Kim Kevin B. , Qin Yong , Cain Suzanne , Washington Edwina W. , Davies Michael A. , Patel Sunil M. , Homsi Jade , Papadopoulos Nicholas E. , Hwu Patrick , Patel Sapna P.
Published: March 2018

Objectives:

Hepatic arterial infusion (HAI) of cytotoxic chemotherapy is a strategy to deliver high dose of anticancer therapy to liver metastases that derive their blood supply from the hepatic artery. Metastatic melanoma (MM) has a high incidence of liver metastases, with uveal subtype in particular exhibiting a predilection for liver dissemination. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) has demonstrated efficacy in MM and first-pass hepatic metabolism. Therefore, we hypothesized that HAI of nab-paclitaxel would deliver an effective dose of drug to the end organ of interest, with minimal systemic exposure.

Patient and Methods:

We performed a single-institution open-label phase I/II study of HAI of nab-paclitaxel in MM patients with liver metastasis. Patients received treatment every 21 days at 4 different dose levels. The primary objective of the phase I portion of the study was safety and determination of the maximum-tolerated dose. The primary objective of the phase II portion of the study was overall response rate per Response Evaluation Criteria In Solid Tumors (RECIST) 1.0.

Results:

A total of 30 patients were treated between 2009 and 2013, 16 of whom had uveal melanoma. The maximum-tolerated dose was 220 mg/m2 and 19 patients were treated at this dose. There was 1 patient (5%) with a partial response at this dose, and 8 patients (42%) with stable disease at this dose.

Conclusions:

HAI nab-paclitaxel demonstrates rare objective responses in melanoma patients with liver metastases. This treatment should be studied in combination with checkpoint blockade or other novel treatments to enhance meaningful responses but should not be considered effective monotherapy.
Mortality Following Hospital Admission for US Active Duty Service Members Diagnosed With Penetrating Traumatic Brain Injury, 2004–2014
Authors: Regasa Lemma Ebssa , Kaplan Dorothy A. , Moy Martin Elisabeth M. , Langbein Jean , Johnson Felicia , Chase LCDR Carla
Published: March 2018

Objective:

To examine mortality among active duty US military service members (SMs) with the diagnosis of penetrating traumatic brain injury (PTBI) and a hospital admission between 2004 and 2014.

Design:

Data on SMs with PTBI and an admission to a military or civilian hospital were obtained from the 2004 to 2014 Military Health System data repository. After applying exclusion criteria, data on 1226 SMs were analyzed.

Main Measures:

The number of observed deaths per 100 identified patients with PTBI and time to death from admission were used as main measures.

Results:

Approximately 25% of the 1226 patients with PTBI included in this study died following admission, with 44.6% of the all deaths occurring within a day following hospital admission and 75% occurring within the first week. Severe comorbid conditions and intentionally self-inflicted injuries are associated with higher mortality rate. SMs' gender, age, year of hospital admission, and service were significantly associated with likelihood of death following PTBI hospitalization. Males had a higher likelihood of dying following hospital admission compared with females (odds ratio = 2.7, confidence interval = 1.03-7.9). SMs in the 35- to 44-year-old and 45- to 64-year-old groups had up to a 2.6 times higher odds of death following their admission compared with the 25- to 34-year-old group. Age, admission year, service, and rank were significantly associated with SMs' time to death from hospitalization. Patients between the ages of 45 and 64 years were significantly more likely to die earlier than other age groups. Furthermore, cases in the Navy Afloat group had a higher fatality rate and were more likely to die earlier than patients in other services. PTBI comorbid conditions and injury type did not significantly affect time to death.

Conclusion:

This study quantifies case fatality rate among hospitalized US SMs with the diagnosis of PTBI. We report a 23.1% crude case fatality rate among the current cohort. Early intensive care for these patients may be the key to improving survival rates.
Adherence to Barcelona Clinic Liver Cancer therapeutic algorithm for hepatocellular carcinoma in the daily practice: a multicenter cohort study from Argentina
Authors: Piñero Federico , Marciano Sebastián , Fernández Nora , Silva Jorge , Zambelo Yanina , Cobos Manuel , Zerega Alina , Ridruejo Ezequiel , Miguez Carlos , Ameigeiras Beatriz , D’Amico Claudia , Gaite Luis , Coronel Matías , Bermúdez Carla , Rosales Carlos , Romero Gustavo , McCormack Lucas , Reggiardo Virginia , Colombato Luis , Gadano Adrián , Rubinstein Fernando , Silva Marcelo
Published: March 2018

Background and aim

Adherence to the Barcelona Clinic Liver Cancer (BCLC) staging algorithm for the treatment of hepatocellular carcinoma is challenging in the daily practice. We aimed to analyze adherence to BCLC along with its effect on patient survival.

Patients and methods

A cohort study was conducted in 14 hospitals from Argentina including patients with newly diagnosed hepatocellular carcinoma (2009–2016). Adherence was considered when the first treatment was the one recommended by the BCLC.

Results

Overall, 708 patients were included. At diagnosis, BCLC stages were as follows: stage 0 4%, A 43%, B 22%, C 9% and D 22%. Overall, 53% of the patients were treated according to BCLC, 24% were undertreated, and 23% overtreated. Adherence to BCLC increased to 63% in subsequent treatments. Independent factors associated with adherence to BCLC were the presence of portal hypertension [odds ratio: 1.63; 95% confidence interval (CI): 1.11–2.39] and BCLC stage C (odds ratio: 0.32; 95% CI: 0.12–0.72). In a multivariable model adjusting for portal hypertension and BCLC stages, adherence to BCLC showed improved survival (hazard ratio: 0.67; 95% CI: 0.52–0.87).

Conclusion

Adherence to BCLC represents a challenge in the daily practice, with almost half of the patients being treated accordingly, showing that the decision-making process should be tailored to each individual patient.
Antiviral treatment of childhood influenza: an update
Authors: Moodley Amaran , Bradley John S. , Kimberlin David W.
Published: March 2018

Purpose of review

Influenza virus can cause severe or life-threatening infection in children. This review provides an update on antiviral medications available to treat and prevent influenza in both healthy children and children with underlying medical conditions, and recommendations on their appropriate use in the outpatient and inpatient settings.

Recent findings

Despite the significant morbidity and mortality associated with influenza infection, a large number of children hospitalized with influenza do not receive specific antiviral treatment with a neuraminidase inhibitor. Although the effectiveness of this intervention has been debated, several recent observational studies have shown the potential benefits conferred by early antiviral treatment. Oral oseltamivir and inhaled zanamivir remain the best studied antiviral agents for influenza treatment and prevention. In addition, the US Food and Drug Administration recently approved peramivir, a novel neuraminidase inhibitor available for intravenous administration.

Children with suspected or documented influenza infection benefit from early antiviral treatment with neuraminidase inhibitors that can shorten illness duration, decrease symptom severity, and lower the risk of complications leading to hospitalization and death. Unless contraindicated, all hospitalized children, children with underlying medical conditions, and those with severe or progressive symptoms of influenza should receive specific antiviral treatment for influenza with a neuraminidase inhibitor. Additionally, antiviral treatment of influenza-infected children in the outpatient setting should be strongly considered.
E and P Selectins as Potential Markers in the Assessment of the Severity of Acute Pancreatitis
Authors: Tsaroucha Alexandra K. , Schizas Dimitrios , Vailas Michail G. , Rachmani Evangelia , Kanavidis Prodromos , Asimakopoulos Vyron , Vlachos Sotirios , Sotiropoulou Maria , Pitiakoudis Michael S. , Simopoulos Constantinos E.
Published: March 2018

Objectives

Acute pancreatitis (AP) is commonly associated with the release of adhesion molecules such as E and P selectins. We designed the present study to evaluate the role of selectins as potential markers that could reflect the severity of the disease.

Methods

One hundred fifty patients with AP constituted the patient group, whereas 70 healthy volunteers established the control group. In both groups, blood samples were taken for measurements of E selectin, P selectin, caspase-cleaved cytokeratin 18, and total soluble cytokeratin 18 levels on admission and days 1, 2, 4, and 6.

Results

Values of E and P selectins on admission were both elevated compared with control subjects (P < 0.01). The nonsurvivors had higher values of E selectin (P < 0.04) and P selectin (P < 0.03) on admission. Levels of E and P selectin showed positive correlation with the length of stay (P < 0.05). E selectin on admission yielded a sensitivity of 75% and 78% specificity, whereas P selectin had a sensitivity of 67% and 91% specificity.

Conclusions

Selectin values in the early course of AP may play a role as indicators of overall prognosis, which may help physicians in better understanding the pathophysiology of a benign disease that may have serious and detrimental complications.
A New 2-Step Acceleration Protocol Using a Histone Deacetylase Inhibitor to Generate Insulin-Producing Cells From Adipose-Derived Mesenchymal Stem Cells
Authors: Ikemoto Tetsuya , Feng Rui , Shimada Mitsuo , Saito Yu , Iwahashi Shuichi , Morine Yuji , Imura Satoru
Published: March 2018

Objectives

We aimed to develop a simple protocol for deriving insulin-producing cells (IPCs) from adipose-derived mesenchymal stem cells (ADSCs). We established a 2-step creation method and an acceleration strategy with a histone deacetylase inhibitor that promoted a pro–endocrine pancreatic lineage.

Methods

We seeded ADSCs in 96-well dishes and cultured in Dulbecco's modified Eagle's medium/F12 medium containing 1% fetal bovine serum, 1% B27 supplement, 1% N2 supplement, 50-ng/mL human activin A, and 10-nM exendin-4 for step 1 of differentiation (7 days). Then 10-mM nicotinamide and 50-ng/mL human hepatocyte growth factor, with or without 1 mM histone deacetylase inhibitor, were added for step 2 of differentiation (14 days). After the 2-step differentiation was complete, cell morphology, immunohistochemistry, messenger RNA expression, and function were investigated.

Results

Our new differentiation protocol with the histone deacetylase inhibitor significantly accelerated IPC differentiation compared with the conventional protocol without the histone deacetylase inhibitor (median, 21.6 vs 38.8 days; P < 0.05). It also improved the islet morphology score (P < 0.05) and the glucose stimulation index (3.1).

Conclusions

By applying our new and easy 2-step protocol using a histone deacetylase inhibitor, ADSCs may be an effective cell source for differentiation of IPCs.
No association of leg strength asymmetry with walking ability, fatigability, and fatigue in multiple sclerosis
Authors: Proessl Felix , Ketelhut Nathaniel B. , Rudroff Thorsten
Published: March 2018

This cross-sectional study aims to determine whether leg strength asymmetries are associated with walking ability, objective measures of fatigability, or subjective perceptions of fatigue. Maximal knee extensor strength was assessed in 19 patients with multiple sclerosis (PwMS), and a symmetry index was calculated. Walking ability was determined through the total distance covered during a 6-min walk test (6MWT) and fatigability by calculating the change in distance covered between minutes 6 and 1. Perceptions of fatigue were assessed using the Fatigue Severity Scale and by obtaining ratings of perceived exertion during the first and final minute of the 6MWT. PwMS covered less distance (P=0.01) and perceived greater exertion (P<0.01) during minute 6 compared with minute 1. Knee extensor strength was asymmetric (P<0.01). The magnitude of asymmetry did not correlate with walking ability, fatigability, or measures of fatigue. Knee extensor strength asymmetry may not play an important role in prolonged walking performance in PwMS.
Association Between Spasticity and Functional Impairments During the First Year After Stroke in Korea
Authors: Shin Yong-Il , Kim Soo-Yeon , Lee Hae In , Kim Deog Young , Lee Jongmin , Sohn Min Kyun , Lee Sam-Gyu , Oh Gyung-Jae , Lee Yang-Soo , Joo Min Cheol , Han Eun Young , Han Junhee , Moon Myung Hoon , Chang Won Hyuk , Kim Youngtaek , Kim Yun-Hee
Published: March 2018

Objective

The aim of the study was to investigate the correlation between spasticity severity and functional outcomes during the first year after stroke.

Design

The Korean Stroke Cohort for Functioning and Rehabilitation is a large, multicenter, prospective cohort study of all patients with acute first-ever stroke admitted to participating hospitals in nine Korean areas. To investigate the correlation between spasticity severity and functional status measured by using the Institutes of Health Stroke Scale (NIHSS), Modified Barthel Index (MBI), Functional Independence Measurement (FIM), Fugl-Meyer Assessment (FMA), Functional Ambulatory Category (FAC), modified Rankin scale (mRS), and American Speech-Language Hearing Association National Outcome Measurement System Swallowing Scale (ASHA-NOMS), data were analyzed at 3, 6, and 12 mos after the occurrence of stroke.

Results

A total of 7359 stroke patients, 3056 were finally included. Prevalence rates of spasticity in patients after stroke were 6.8% at 3 mos, 6.9% at 6 mos, and 7.6% at 12 mos. The scores of mRS and NIHSS were higher and those of K-MBI, FIM, FMA, and ASHA-NOMS were lower in more severe spastic patients, indicating poorer functional outcomes (P < 0.05).

Conclusions

This study demonstrated the coexistence of spasticity and poor functional outcome during the first year after first-ever stroke patients.
The International Association for the Study of Pain definition of pain: as valid in 2018 as in 1979, but in need of regularly updated footnotes
Authors: Treede Rolf-Detlef
Published: March 2018

Milton Cohen, John Quintner, and Simon van Rysewyk proposed a revision of the IASP definition of pain of 1979. This commentary summarizes, why this proposal is useful for guiding assessment of pain, but not its definition.
Minimal Disease Activity and Patient-Acceptable Symptom State in Psoriatic Arthritis
Authors: Queiro Rubén , Brandy Anahy , Rosado Mª Carmen , Lorenzo Andrés , Coto Pablo , Carriles Carmen , Alperi Mercedes , Ballina Javier
Published: March 2018

Background/aims

Ustekinumab (UST) is a fully human immunoglobulin G1 monoclonal antibody approved for treating moderate to severe psoriasis and, more recently, psoriatic arthritis (PsA) as well. However, information regarding its clinical usefulness in a real-world setting is scarce. We aimed to evaluate the effectiveness and safety of UST in a real-world clinical setting.

Methods

This single-center observational study included PsA outpatients (n = 50) treated with UST from March 2015 to March 2017. Only patients who used at least 3 doses of UST were analyzed. The percentage of patients who achieved a minimal disease activity (MDA) response was collected. The impact of the disease was also evaluated according to the recently developed Psoriatic Arthritis Impact of Disease (PsAID) questionnaire. A binary logistic regression multivariate model was performed to look for variables predicting MDA.

Results

Twenty-seven patients (54%) reached an MDA state. Mean PsAID in MDA group was 3.5 ± 2.9 versus 6.8 ± 5.1 in non-MDA patients (p < 0.001). Among the patients who achieved MDA, 19 (70.4%) had a patient-acceptable symptom state according to the PsAID, whereas only 5 (21.7%) of the 23 patients who did not reach an MDA achieved a patient-acceptable symptom state (p < 0.001). Higher basal Psoriasis Area and Severity Index decreased the odds of achieving MDA (odds ratio [OR], 0.80; 95% CI, 0.65–0.99; p = 0.038), whereas a longer use of UST (OR, 1.52; 95% CI, 1.13–2.06; p = 0.015) and a previous failure to 1 anti–tumor necrosis factor α (OR, 18; 95% CI, 2.52–128.63; p = 0.004) increased this odds. We found no major safety problems.

Conclusions

Ustekinumab was effective and safe in this PsA population. Minimal disease activity and PsAID may be useful tools in the evaluation of PsA therapeutic interventions in routine clinical practice.
Duration of Catheterization After Retropubic Midurethral Sling
Authors: Geynisman-Tan Julia , Dave-Heliker Bhumy , Bochenska Katarzyna , Collins Sarah , Lewicky-Gaupp Christina , Mueller Margaret , Kenton Kimberly
Published: March 2018

Objective

The objective of this study was to describe the expected duration of self-catheterization in women discharged home performing intermittent self-catheterization (ISC) after retropubic midurethral sling (RMUS).

Methods

We conducted a retrospective cohort analysis of women who underwent an isolated RMUS by 3 providers between 2009 and 2014 at a single institution. A 300 mL retrograde-fill voiding trial (VT) was performed before discharge. Those who failed their VT (postvoid residual [PVR] >1/3 total bladder volume [TBV]) and could perform ISC are included in this analysis. Subjects were categorized into mild retention (PVR >1/3 and <2/3 the TBV) or severe retention (PVR ≥2/3 the TBV). Patients could discontinue ISC after achieving 2 consecutive PVR volumes of less than 75 mL. Duration of catheterization was determined in days.

Results

Two hundred women underwent isolated RMUS. Forty-seven (23.5%) failed their VT of whom 39 (included in this analysis) could perform ISC and had complete data. Subjects had a mean ± SD age of 49 ± 11 years. The median (interquartile range) PVR volume postoperatively was 250 (190–325) mL. Median (interquartile range) days of postoperative ISC for the cohort was 2 (1–4); 37.5% were catheterized for 1 day, 32.5% for 2 days, 2.5% for 3 days, and 27.5% for more than 3 days. Seventeen (39.5%) met the criteria for mild retention and 26 (60.5%) met the criteria for severe retention. There was no difference in the postoperative catheterization days between the mild and severe retention groups (P = 0.16).

Conclusions

Urinary retention will resolve within 2 days in the majority (73%) of women discharged performing ISC after RMUS.
Evans function computation for the stability of travelling waves
Authors: Barker B. , Humpherys J. , Lyng G. , Lytle J.
Published: March 2018

In recent years, the Evans function has become an important tool for the determination of stability of travelling waves. This function, a Wronskian of decaying solutions of the eigenvalue equation, is useful both analytically and computationally for the spectral analysis of the linearized operator about the wave. In particular, Evans-function computation allows one to locate any unstable eigenvalues of the linear operator (if they exist); this allows one to establish spectral stability of a given wave and identify bifurcation points (loss of stability) as model parameters vary. In this paper, we review computational aspects of the Evans function and apply it to multidimensional detonation waves.

This article is part of the theme issue ‘Stability of nonlinear waves and patterns and related topics’.
Instability of pulses in gradient reaction–diffusion systems: a symplectic approach
Authors: Beck M. , Cox G. , Jones C. , Latushkin Y. , McQuighan K. , Sukhtayev A.
Published: March 2018

In a scalar reaction–diffusion equation, it is known that the stability of a steady state can be determined from the Maslov index, a topological invariant that counts the state’s critical points. In particular, this implies that pulse solutions are unstable. We extend this picture to pulses in reaction–diffusion systems with gradient nonlinearity. In particular, we associate a Maslov index to any asymptotically constant state, generalizing existing definitions of the Maslov index for homoclinic orbits. It is shown that this index equals the number of unstable eigenvalues for the linearized evolution equation. Finally, we use a symmetry argument to show that any pulse solution must have non-zero Maslov index, and hence be unstable.

This article is part of the theme issue ‘Stability of nonlinear waves and patterns and related topics’.
An energy-based stability criterion for solitary travelling waves in Hamiltonian lattices
Authors: Xu Haitao , Cuevas-Maraver Jesús , Kevrekidis Panayotis G. , Vainchtein Anna
Published: March 2018

In this work, we revisit a criterion, originally proposed in Friesecke & Pego (Friesecke & Pego 2004Nonlinearity17, 207–227. (doi:10.1088/0951715/17/1/013)), for the stability of solitary travelling waves in Hamiltonian, infinite-dimensional lattice dynamical systems. We discuss the implications of this criterion from the point of view of stability theory, both at the level of the spectral analysis of the advance-delay differential equations in the co-travelling frame, as well as at that of the Floquet problem arising when considering the travelling wave as a periodic orbit modulo shift. We establish the correspondence of these perspectives for the pertinent eigenvalue and Floquet multiplier and provide explicit expressions for their dependence on the velocity of the travelling wave in the vicinity of the critical point. Numerical results are used to corroborate the relevant predictions in two different models, where the stability may change twice. Some extensions, generalizations and future directions of this investigation are also discussed.

This article is part of the theme issue ‘Stability of nonlinear waves and patterns and related topics’.
An unusual case of congestive heart failure in the Netherlands
Authors: Persoon Marjolein C. , Manintveld Olivier C. , Mollema Femke P. N. , van Hellemond Jaap J.
Published: March 2018

Introduction. Chagas disease is caused by infection with the protozoan Trypanosoma cruzi. It is endemic to the American continent due to the distribution of its insect vectors. The disease is occasionally imported to other continents by travel of infected individuals. It is rarely diagnosed in the Netherlands and exact numbers of infected individuals are unknown. Clinical manifestations can start with an acute phase of 4–8 weeks with non-specific, mild symptoms and febrile illness. In the chronic phase, it can lead to fatal cardiac and gastro-intestinal complications.

Case presentation. We describe a case of a 40-year-old man with end-stage cardiomyopathy due to Chagas disease. He lived in Surinam for more than 20 years and had an unremarkable medical history until he was hospitalized due to pneumonia and congestive heart failure. Despite antibiotic treatment and optimizing cardiac medication, his disease progressed to end-stage heart failure for which cardiac transplantation was the only remaining treatment. A left ventricular assist device (LVAD) was implanted as a bridge to transplantation. Tissue analysis after LVAD surgery revealed ongoing myocarditis caused by Chagas disease. Based on a literature review, a scheme for follow up and treatment after transplantation was postulated.

Conclusion. Chagas disease should be taken into account in patients from endemic countries who have corresponding clinical signs. Heart transplantation in patients with Chagas cardiomyopathy is accompanied by specific challenges due to the required immunosuppressive therapy and the thereby increased risk of reactivation of a latent T. cruzi infection.
Rare and common vertebrates span a wide spectrum of population trends
Authors: Daskalova Gergana N. , Myers-Smith Isla H. , Godlee John L.
Published: March 2018

The Earth’s biota is changing over time in complex ways. A critical challenge is to test whether specific biomes, taxa or types of species benefit or suffer in a time of accelerating global change. We analysed nearly 10 000 abundance time series from over 2000 vertebrate species part of the Living Planet Database. We integrated abundance data with information on geographic range, habitat preference, taxonomic and phylogenetic relationships, and IUCN Red List Categories and threats. We found that 15% of populations declined, 18% increased, and 67% showed no net changes over time. Against a backdrop of no biogeographic and phylogenetic patterning in population change, we uncovered a distinct taxonomic signal. Amphibians were the only taxa that experienced net declines in the analysed data, while birds, mammals and reptiles experienced net increases. Population trends were poorly captured by species’ rarity and global-scale threats. Incorporation of the full spectrum of population change will improve conservation efforts to protect global biodiversity.
Chimpanzees but not orangutans display aversive reactions toward their partner receiving a superior reward
Authors: Kim Yena , Choe Jae , Jeong Gilsang , Kim Dongsun , Tomonaga Masaki
Published: March 2018

Fairness judgment is a fundamental aspect of human cooperation. By carefully balancing the payoffs and efforts with cooperating partner (s) we could either avoid or punish cheaters and stably maintain cooperation. Recent studies investigating the origin of this fairness sentiment have demonstrated that this psychological trait is not unique to humans, but also can be observed in other group-living primates, such as chimpanzees and capuchins, suggesting a convergent evolution of a sense of fairness, with cooperative social life being the selective pressure for it. The current study was designed to test this hypothesis by directly comparing the response to the outcome inequity in two of our closest living relatives, chimpanzees and orangutans, having different social systems, i.e. solitary and patrilocal multi-male multi-female groups. Unlike other inequity experiments, we used a prosocial choice apparatus with different reward distributions (advantageous / disadvantageous) to give subjects an active role of not-sharing foods if they considered it unfair. In addition to the choice, we also recorded the behavioral responses of the apes to the inequity. Throughout the experiments aversive emotional responses toward the disadvantageous inequity were only found in chimpanzees, but not in orangutans, supporting the convergent (or domain-specific) evolution of a sense of fairness. However, this aversion to the inequity did not lead the chimpanzees to actually make selfish choices, indirectly supporting the previous findings that chimpanzees employ a partner choice strategy rather than a punishment for fair cooperation. We also found that hierarchy seems to play an important role in the expression of aversion to inequity and prosocial tendency in chimpanzees.
Scalable cytoarchitectonic characterization of large intact human neocortex samples
Authors: Hildebrand Sven , Schueth Anna , Herrler Andreas , Galuske Ralf , Roebroeck Alard
Published: March 2018

We describe MASH (Multiscale Architectonic Staining of Human cortex): a simple, fast and low-cost cytoarchitectonic labeling and optical clearing approach for human cortex samples, which can be applied to large formalin fixed adult brain samples. A suite of small-molecule fluorescent nuclear and cytoplasmic dyes in combination with new refractive index matching solutions allows deep volume imaging. This enables highly scalable human neocortical cytoarchitecture characterization with a large 3D scope.
A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus
Authors: Chao Day-Yu , Shen Wen-Fan , Galula Jedhan Ucat , Liu Jiun-Hung , Liao Mei-Ying , Huang Chang-Hao , Wang Yu-Chun , Wu Han-Chung , Liang Jian-Jong , Lin Yi-Ling , Whitney Matthew T. , Chang Gwong-Jen J. , Chen Sheng-Ren , Wu Shang-Rung
Published: March 2018

Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. The vaccine candidates under development require a tetravalent immunogen to induce a balanced immunity against all four serotypes of dengue virus. Herein we show that mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher and broader neutralization antibodies (NtAbs) against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. The cryo-electron microscopy reconstruction showed that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Most importantly, maternally transferred antibodies derived from mD2VLP-vaccinated female mice protected suckling mice from lethal challenge by all four serotypes of DENV. Our results support the fact that a universal dengue vaccine that protects against all four serotypes of dengue viruses can be achieved by using an immunogen such as mD2VLP.
A protocol for single-cell transcriptomics from cryopreserved renal tissue and urine for the Accelerating Medicine Partnership (AMP) RA/SLE network
Authors: Rao Deepak A. , Berthier Celine C. , Arazi Arnon , Davidson Anne , Liu Yanyan , Browne Edward P. , Eisenhaure Thomas M. , Chicoine Adam , Lieb David J. , Smilek Dawn E. , Tosta Patti , Lederer James A. , Brenner Michael B. , Hildeman David , Woodle E. Steve , Wofsy David , Anolik Jennifer H. , Kretzler Matthias , Hacohen Nir , Diamond Betty
Published: March 2018

OBJECTIVE

There is a critical need to define the cells that mediate tissue damage in lupus nephritis. Here we aimed to establish a protocol to preserve lupus nephritis kidney biopsies and urine cell samples obtained at multiple clinical sites for subsequent isolation and transcriptomic analysis of single cells.

METHODS

Fresh and cryopreserved kidney tissue from tumor nephrectomies and lupus nephritis kidney biopsies were disaggregated by enzymatic digestion. Cell yields and cell composition were assessed by flow cytometry. Transcriptomes of leukocytes and epithelial cells were evaluated by low-input and single cell RNA-seq.

RESULTS

Cryopreserved kidney tissue from tumor nephrectomies and lupus nephritis biopsies can be thawed and dissociated to yield intact, viable leukocytes and epithelial cells. Cryopreservation of intact kidney tissue provides higher epithelial cell yields compared to cryopreservation of single cell suspensions from dissociated kidneys. Cell yields and flow cytometric cell phenotypes are comparable between cryopreserved kidney samples and paired kidney samples shipped overnight on wet ice. High-quality single cell and low-input transcriptomic data were generated from leukocytes from both cryopreserved lupus nephritis kidney biopsies and urine, as well as from a subset of kidney epithelial cells.

CONCLUSION

The AMP RA/SLE cryopreserved tissue analysis pipeline provides a method for centralized processing of lupus nephritis kidney biopsies and urine samples to generate robust transcriptomic analyses in multi-center studies.
Heterogeneous local dynamics revealed by classification analysis of spatially disaggregated time series data
Authors: Perkins T. Alex , Rodriguez-Barraquer Isabel , Manore Carrie , Siraj Amir S. , España Guido , Barker Christopher M. , Johansson Michael A. , Reiner Robert C.
Published: March 2018

Time series data provide a crucial window into infectious disease dynamics, yet their utility is often limited by the spatially aggregated form in which they are presented. When working with time series data, violating the implicit assumption of homogeneous dynamics below the scale of spatial aggregation could bias inferences about underlying processes. We tested this assumption in the context of the 2015-2016 Zika epidemic in Colombia, where time series of weekly case reports were available at national, departmental, and municipal scales. First, we performed a descriptive analysis, which showed that the timing of departmental-level epidemic peaks varied by three months and that departmental-level estimates of the time-varying reproduction number, R(t), showed patterns that were distinct from a national-level estimate. Second, we applied a classification algorithm to six features of proportional cumulative incidence curves, which showed that variability in epidemic duration, the length of the epidemic tail, and consistency with a cumulative normal density curve made the greatest contributions to distinguishing groups. Third, we applied this classification algorithm to data simulated with a stochastic transmission model, which showed that group assignments were consistent with simulated differences in the basic reproduction number, R0. This result, along with associations between spatial drivers of transmission and group assignments based on observed data, suggests that the classification algorithm is capable of detecting differences in temporal patterns that are associated with differences in underlying drivers of incidence patterns. Overall, this diversity of temporal patterns at local scales underscores the value of spatially disaggregated time series data.
A method for simultaneous targeted mutagenesis of all nuclear rDNA repeats in Saccharomyces cerevisiae using CRISPR-Cas9
Authors: Chiou Lilly , Armaleo Daniele
Published: March 2018

Saccharomyces cerevisiae has been the prime model to study the assembly and functionality of eukaryotic ribosomes. Within that vast landscape, the specific problem of mutagenizing all 150 nuclear rRNA genes was bypassed using strains whose chromosomal copies had been deleted and substituted by plasmid-borne rDNA. Work with these strains has produced important insights, but nucleolar structure is altered and such yeast-specific approaches are elaborate and not transferable to most other eukaryotes. We describe here a simple CRISPR-Cas9 based method to place targeted mutations in all 150 chromosomal rDNA repeats in yeast. The procedure per se is not expected to alter the nucleolus and is potentially applicable also to other eukaryotes. Yeast was transformed with a plasmid bearing the genes for Cas9 and for the guide RNA, engineered to target a site in the SSU region. Our mutagenesis plan included insertion of a spliceosomal intron in the normally intronless yeast nuclear rDNA. Despite the potential lethality of cutting all 150 rDNA repeats at the same time, yeast survived the Cas9 attack through inactivation of the cut sites either by point mutations or by inserting the intron, which was spliced out correctly from the rRNA transcript. In each mutant strain the same mutation was present in all rDNA repeats and was stably inherited even after removal of the Cas9 plasmid.
Visualizing and interpreting single-cell gene expression datasets with Similarity Weighted Nonnegative Embedding
Authors: Wu Yan , Tamayo Pablo , Zhang Kun
Published: March 2018

High throughput single-cell gene expression profiling has enabled the characterization of novel cell types and developmental trajectories. Visualizing these datasets is crucial to biological interpretation, and the most popular method is t-Stochastic Neighbor embedding (t-SNE), which visualizes local patterns better than other methods, but often distorts global structure, such as distances between clusters. We developed Similarity Weighted Nonnegative Embedding (SWNE), which enhances interpretation of datasets by embedding the genes and factors that separate cell states alongside the cells on the visualization, captures local structure better than t-SNE and existing methods, and maintains fidelity when visualizing global structure. SWNE uses nonnegative matrix factorization to decompose the gene expression matrix into biologically relevant factors, embeds the cells, genes and factors in a 2D visualization, and uses a similarity matrix to smooth the embeddings. We demonstrate SWNE on single cell RNA-seq data from hematopoietic progenitors and human brain cells.
Curating clinically relevant transcripts for the interpretation of sequence variants
Authors: DiStefano Marina T. , Hemphill Sarah E. , Cushman Brandon J. , Bowser Mark J. , Hynes Elizabeth , Grant Andrew R. , Siegert Rebecca K. , Oza Andrea M. , Gonzalez Michael A. , Amr Sami S. , Rehm Heidi L. , Abou Tayoun Ahmad N.
Published: March 2018

Variant interpretation depends on accurate annotations using biologically relevant transcripts. We have developed a systematic strategy for designating primary transcripts, and applied it to 109 hearing loss-associated genes that were divided into 3 categories. Category 1 genes (n=38) had a single transcript, Category 2 genes (n=32) had multiple transcripts, but a single transcript was sufficient to represent all exons, and Category 3 genes (n=38) had multiple transcripts with unique exons. Transcripts were curated with respect to gene expression reported in the literature and the Genotype-Tissue Expression Project. In addition, high frequency loss of function variants in the Genome Aggregation Database, and disease-causing variants in ClinVar and the Human Gene Mutation Database across the 109 genes were queried. These data were used to classify exons as "clinically relevant", "uncertain significance", or "clinically insignificant". Interestingly, 7% of all exons, containing >124 "clinically significant" variants, were of “uncertain significance”. Finally, we used exon-level next generation sequencing quality metrics generated at two clinical labs, and identified a total of 43 technically challenging exons in 20 different genes that had inadequate coverage and/or homology issues which might lead to false variant calls. We have demonstrated that transcript analysis plays a critical role in accurate clinical variant interpretation.
An improved method for fitting gamma distribution to substitution rate variation among sites
Authors: Xia Xuhua
Published: March 2018

Gamma distribution has been used to fit substitution rate variation over site. One simple method to estimate the shape parameter of the gamma distribution is to 1) reconstruct a phylogenetic tree and the ancestral states of internal nodes, 2) perform pairwise comparison between nodes on each side of each branch to count the number of “observed” substitutions for each site, and apply correction of multiple hits to derive the estimated number of substitutions for each site, and 3) fit the site-specific substitution data to gamma distribution to obtain the shape parameter α This method is fast but its accuracy depends much on the accuracy of the estimated site-specific number of substitutions. The existing method has three shortcomings. First, it uses Poisson correction which is inadequate for almost any nucleotide sequences. Second, it does independent estimation for the number of substitutions at each site without making use of information at all sites. Third, the program implementing the method has never been made publically available. I have implemented in DAMBE software a new method based on the F84 substitution model with simultaneous estimation that uses information from all sites in estimating the number of substitutions at each site. DAMBE is freely available at available athttp://dambe.bio.uottawa.ca