bluuebunny/crossref_metadata_2025 huggingface dataset:
The KSEA App: a web-based tool for kinase activity inference from quantitative phosphoproteomics
Authors: Wiredja Danica D , Koyutürk Mehmet , Chance Mark R
Published: June 2017

Computational characterization of differential kinase activity from phosphoproteomics datasets is critical for correctly inferring cellular circuitry and how signaling cascades are altered in drug treatment and/or disease. Kinase-Substrate Enrichment Analysis (KSEA) offers a powerful approach to estimating changes in a kinase’s activity based on the collective phosphorylation changes of its identified substrates. However, KSEA has been limited to programmers who are able to implement the algorithms. Thus, to make it accessible to the larger scientific community, we present a web-based application of this method: the KSEA App. Overall, we expect that this tool will offer a quick and user-friendly way of generating kinase activity estimates from high-throughput phosphoproteomics datasets.

Availability and implementation

the KSEA App is a free online tool: casecpb.shinyapps.io/ksea/. The source code is on GitHub: github.com/casecpb/KSEA/. The application is also available as the R package ‘KSEAapp’ on CRAN: CRAN.R-project.org/package=KSEAapp/.

Supplementary information

Supplementary data are available at Bioinformatics online.
KIC 8462852: Will the Trojans return in 2021?
Authors: Ballesteros Fernando J , Arnalte-Mur Pablo , Fernandez-Soto Alberto , Martínez Vicent J
Published: June 2017

KIC 8462852 stood out among more than 100 000 stars in the Kepler catalogue because of the strange features of its light curve: a wide, asymmetric dimming taking up to 15 per cent of the light at D793 and a period of multiple, narrow dimmings happening approximately 700 d later. Several models have been proposed to account for this abnormal behaviour, most of which require either unlikely causes or a finely tuned timing. We aim at offering a relatively natural solution, invoking only phenomena that have been previously observed, although perhaps in larger or more massive versions. We model the system using a large, ringed body whose transit produces the first dimming and a swarm of Trojan objects sharing its orbit that causes the second period of multiple dimmings. The resulting orbital period is T ≈ 12 yr, with a semi-major axis a ≈ 6 au. Our model allows us to make two straightforward predictions: we expect the passage of a new swarm of Trojans in front of the star starting during the early months of 2021, and a new transit of the main object during the first half of 2023.
The Effect of Hearing Loss on Novel Word Learning in Infant- and Adult-Directed Speech
Authors: Robertson V. Susie , von Hapsburg Deborah , Hay Jessica S.
Published: June 2017

Objectives:

Relatively little is known about how young children with hearing impairment (HI) learn novel words in infant- and adult-directed speech (ADS). Infant-directed speech (IDS) supports word learning in typically developing infants relative to ADS. This study examined how children with normal hearing (NH) and children with HI learn novel words in IDS and ADS. It was predicted that IDS would support novel word learning in both groups of children. In addition, children with HI were expected to be less proficient word learners as compared with their NH peers.

Design:

A looking-while-listening paradigm was used to measure novel word learning in 16 children with sensorineural HI (age range 23.2 to 42.1 months) who wore either bilateral hearing aids (n = 10) or bilateral cochlear implants (n = 6) and 16 children with NH (age range 23.1 to 42.1 months) who were matched for gender, chronological age, and maternal education level. Two measures of word learning were assessed (accuracy and reaction time). Each child participated in two experiments approximately 1 week apart, one in IDS and one in ADS.

Results:

Both groups successfully learned the novel words in both speech type conditions, as evidenced by children looking at the correct picture significantly above chance. As a group, children with NH outperformed children with HI in the novel word learning task; however, there were no significant differences between performance on IDS versus ADS. More fine-grained time course analyses revealed that children with HI, and particularly children who use hearing aids, had more difficulty learning novel words in ADS, compared with children with NH.

Conclusions:

The pattern of results observed in the children with HI suggests that they may need extended support from clinicians and caregivers, through the use of IDS, during novel word learning. Future research should continue to focus on understanding the factors (e.g., device type and use, age of intervention, audibility, acoustic characteristics of input, etc.) that may influence word learning in children with HI in both IDS and ADS.
Does the degree of beach chair position during shoulder arthroscopy affect cerebral oxygenation? A prospective comparative study
Authors: Ghandour Tarek Mohamed , Ahmed Abdelrahman Amr , Mohamed Ibrahim Amr , Zaki Michel Badie
Published: June 2017

Background:

The aim of this prospective cohort study was to determine the incidence of cerebral desaturation events (CDE) in patients undergoing shoulder arthroscopy in the beach chair position (BCP) compared to patients undergoing shoulder arthroscopy in the semi-upright sitting position (SSP).

Methods:

This prospective study included 220 patients, 150 men (68.18%) and 70 women (31.82%). The average age was 46 yr (24-68) years. Patients under 18 yr of age, those with uncontrolled diabetes, a previous cerebral stroke, a myocardial infarction, rheumatoid arthritis, congestive heart failure, severe cervical disc prolapsed, or severe obesity (body mass index >30) were excluded from the study. The patients were divided into two groups (110 patients in each group). Group A patients had shoulder arthroscopy done in the 60-degree beach chair position and Group B had shoulder arthroscopy done in a semi-upright sitting position at 90 degrees. Mean arterial blood pressure and cerebral oxygen saturation were measured at different stages: before induction of anesthesia (T0), after induction (T1 [baseline]), after positioning (T2), after induction of hypotension (T3), and 1 hr after final position (T4). Cerebral desaturation was defined as a reduction in regional cerebral oxygen saturation to less than 80% of baseline value for 15 sec or longer. Each stage was compared with others in the same group and with the other group.

Results:

In both groups, the mean arterial blood pressure (MAP) values at T2 were significantly lower than at T1. The MAP values at T3 and T4 were significantly lower than those at T1 and T2. There was a significant decrease in regional cerebral oxygen saturation in stage T3 when compared to previous stages in the same group. Without any significant decrease in stage T4 compared to T3 in the same group. We found no significant difference in regional cerebral oxygen saturation when comparing each stage in both groups.

Conclusions:

No significant difference was noted in regional cerebral oxygen saturation between patients operated on in the beach chair position and those operated on in the semi-upright sitting position. A direct relation was noted between the decrease in mean arterial pressure and decrease in cerebral oxygen saturation.
Salvage of failed ankle arthrodesis after posttraumatic septic arthritis by Ilizarov external fixator: mid-term results
Authors: Ahmed Abdel-Salam A. , Singer Mohammed S.
Published: June 2017

Background:

Failed septic ankle arthrodesis is a challenging problem. This study evaluated the results of salvage revision ankle arthrodesis using Ilizarov external fixation to treat nonunited arthrodesis of posttraumatic septic ankle arthritis and to analyze the functional outcome of this method.

Methods:

This prospective study included 14 patients with a mean age of 48 yr. Patients had already undergone a mean of 4.43 previous surgeries at a mean of 17.14 mo from primary arthrodesis. Five patients had associated deformity. The mean preoperative American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score was 23.93. Meticulous debridement was done and an Ilizarov fixator was applied in compression in a one-stage procedure.

Results:

The mean follow up period was 41.71 mo with mean external fixation period of 17.29 wk. Successful arthrodesis in perfect alignment was achieved in 13 of 14 patients without additional procedures. One ankle did not go on to union. A chronic discharging sinus persisted in one patient. One infected loose wire was exchanged in two patients. One diabetic patient reported moderate daily diffuse pain. The mean postoperative AOFAS ankle-hindfoot score was 71.57. Patients with successful fusion were satisfied with the procedure.

Conclusions:

Using an Ilizarov fixator to salvage nonunited septic posttraumatic ankle arthrodesis was effective, with patients reporting a stable ankle and dramatic functional improvement with minimal complications.
Factors predicting admission to extended care facility after distal femoral fracture
Authors: Boin Michael A. , Narayanan Shankar , Duren Dana , Dorweiler Matthew , Lee Jessica , Froehle Andrew , Laughlin Richard
Published: June 2017

Background:

Delayed identification of patients requiring admission to an extended care facility (ECF) after orthopaedic injuries is leading to delays in discharge. The aim of this study was to identify patient factors that predict the need for admission to an ECF after distal femoral fracture.

Methods:

A retrospective chart review was performed in 176 patients admitted with a distal femoral fracture at a level one trauma center. Patient characteristics, medical comorbidities, and fracture classification were among the variables analyzed. Discriminate function analysis was used to predict if a patient would need an ECF after their hospital stay.

Results:

Seventy-one patients were included in the final statistical analysis. Of these, 11 men (48%) and 40 women (83%) were discharged to an ECF. Analysis demonstrated that higher American Society of Anesthesiologist (ASA) score (P<0.001), higher body mass index (BMI) (P<0.02), diabetes (P<0.03), and periprosthetic fracture (P<0.04) for men, while a higher ASA score (P<0.001) and lower hemoglobin (P<0.05) for women were the key variables in predicting discharge to an ECF. Using these variables, we developed a predictive equation that correctly classified 95.7% of men and 81.3% of women as requiring an ECF.

Conclusions:

We were able to distinguish patient factors that predicted discharge to an ECF. Patient care providers can use these findings to proactively identify those who will need an ECF and potentially decrease nonmedical delays in discharge.
Stiffness after primary total knee arthroplasty: a radiographic analysis with a matched-control population
Authors: Moya-Angeler Joaquin , Bas Marcel A. , Cooper H. John , Hepinstall Matthew S. , Rodriguez Jose A. , Scuderi Giles R.
Published: June 2017

Background:

The purposes of this study were (1) to evaluate standardized radiographic parameters in a population of patients who developed stiffness after primary total knee arthroplasty (TKA), and (2) to compare those to a matched control population.

Methods:

A retrospective review was performed to identify patients who required revision for stiffness after primary TKA. Patients with history of TKA revision or infection, as well as, those treated with isolated polyethylene exchange were excluded. Study patients were matched 1:1 with controls based on age, sex, body mass index (BMI). Radiographic measurements were performed by two blinded independent observers.

Results:

A total of 44 patients met the inclusion criteria. Thirty-one (70%) were females. Mean BMI was 33 kg/m2 (19-58). Univariate odds ratios showed significance for patella baja (5.776; 0.025), increased anterior condylar offset ratio (ACO) (15.265; 0.000), increased anterior implant-cortex gap (5.067; 0.038), and increased percentage of patellar displacement (PPD) (6.476; 0.016). Multivariate regression analysis showed significance for ACO (18.307; 0.001) and PPD (9.338; 0.024). No significance was observed with respect to component alignment in the coronal or sagittal planes, posterior condylar offset ratio, patellar tilt, presence of heterotopic ossification, or posterior osteophyte formation. Intraclass correlation coefficients (ICCs) ranged from good to excellent (>0.8) for all measurements performed.

Conclusions:

The restoration of the joint line and avoiding overstuffing the patellofemoral compartment are fundamental in preventing the development of postoperative stiffness. Poor mechanics of the patellofemoral compartment are significantly associated with the development of stiffness after primary TKA.
Second Place Award: Tranexamic acid and intrathecal morphine are synergistic in reducing transfusion requirements in pediatric posterior spinal fusion
Authors: Schur Mathew D. , Blumstein Gideon W. , Ross Patrick A. , Andras Lindsay M. , Skaggs David L.
Published: June 2017

Background:

Previous studies demonstrated that the independent use of both tranexamic acid (TXA) and intrathecal morphine (ITM) reduced transfusion requirements in scoliosis patients undergoing posterior spinal fusion (PSF). This study examined the combined effects of TXA and ITM on transfusion requirements in pediatric patients undergoing PSF.

Methods:

A retrospective review of consecutive patients treated with PSF at a single institution was performed. Patients with a minimum of 10 vertebral levels of fusion and PSF with segmental instrumentation were included. Transfusion records were reviewed during surgery and 7 days postoperatively. Patients were divided into four treatment groups for comparison: 1. No TXA, No ITM; 2. Only TXA; 3. Only ITM and 4. TXA and ITM. Multivariate regression analysis, Student t-test, and chi-squared test were used to determine significance.

Results:

Five hundred and ninety-four patients met inclusion criteria; 63% (376/594) were female, average age: 14.6 yr (range 8.0-24.3 yr) and average 13 levels fused (10-18 levels). Fifty-three percent (316/594) received packed red blood cell (PRBC) transfusion. Patients receiving the TXA and ITM combination had 72% lower odds ratio of transfusion (P<0.001, OR 0.28, CI 0.14-0.56). Patients did not have lower odds ratio of transfusion when receiving TXA alone (P=0.32, OR 0.65, CI 0.28-1.53) or ITM alone (P=0.09, OR 0.55, CI 0.28-1.09). Similar results were seen when patients were analyzed separately by diagnosis (idiopathic vs. nonidiopathic).

Conclusions:

The combination of TXA and ITM was associated with 72% reduction in odds ratio of PRBC transfusion in pediatric patients undergoing PSF, an effect seen in both idiopathic and nonidiopathic scoliosis when analyzed separately.
Clinical outcomes of single-incision suture anchor repair of distal biceps tendon rupture
Authors: Dupaix John P. , Kuba Megan H.M. , Atkinson Robert E. , Singer Daniel I. , Chock Megan M. , Napier Erin
Published: June 2017

Background:

Rupture of the distal biceps tendon remains an uncommon injury that is ideally treated by operative repair. Single-incision anterior approach with suture anchor repair is one such method. The purpose of this study was to describe the outcomes in patients who underwent repair of the distal biceps tendon with single anterior incision and suture anchor repair.

Methods:

One hundred and nineteen patients (120 repairs) with distal biceps tendon repairs between January 1, 2002 and December 31, 2012 were identified and their charts retrospectively reviewed. Twenty-five of these patients participated in additional collection of outcome data including range of motion, strength, pain, satisfaction, and clinical outcome.

Results:

In the retrospective analysis, the population was 93% male. Average age was 47.3 yr; however, females had a significantly higher mean age (62.5). Most of the patients (69.8%) returned to full or partial work. The additional data collection cohort reported high satisfaction, little-to-no pain on visual analog scale (VAS) and average Disability of the Arm Shoulder and Hand (DASH) scores. Patients with workers’ compensation claims reported significantly higher pain and worse DASH scores. There was small but significant loss of pronation, and a small loss of grip strength that approached significance.

Conclusions:

Single anterior incision with suture anchor repair may be utilized for repair of ruptures of the distal biceps tendon with good clinical and functional outcomes and minimal loss of range of motion and strength. Females tend to be older at presentation than males with this condition. As in other studies, workers’ compensation claims were associated with poorer clinical outcomes.

Level of Evidence:

Therapeutic, level IV, case series study.
Third Place Award: Posttraumatic elbow arthrofibrosis incidence and risk factors: a retrospective review
Authors: Marchand Lucas S. , Working Zachary M. , Williams John B. , Elliott Iain S. , Higgins Thomas F. , Rothberg David L. , Kubiak Erik N.
Published: June 2017

Background:

Loss of elbow range of motion (ROM) can significantly decrease patient quality of life. Posttraumatic arthrofibrosis is a common cause of decreased elbow ROM, and it has been reported that loss of 50% of elbow motion can compromise 80% of extremity function. The aim of this study was to examine the incidence and risk factors of posttraumatic elbow arthrofibrosis.

Methods:

We performed a retrospective review of all patients with intraarticular elbow fracture treated with operative fixation over a 10-year period. Pearson’s Chi-squared, Student’s t-test, and a logistic multivariate regression model was used to predict arthrofibrosis risk factors.

Results:

A total of 390 consecutive patients with intra-articular elbow fractures were identified. A total of 105 (27%) patients developed arthrofibrosis with 72 surgical interventions performed to improve ROM. At final follow-up 88 (23%) patients had persistent arthrofibrosis. Using multivariate regression analysis, high-energy mechanism (odds ratio (OR) 3.61, 95% confidence interval (CI) 1.16-6.3, P<0.001), deep post operative infection (OR 2.3, 95% CI 1.26-4.37, P=0.038), elbow fracture-dislocations (OR 3.44, 95% CI 1.32-7.41, P=0.005), and distal humeral fractures (OR 1.9, 95% CI 1.1-3.19, P=0.027) were significantly associated with the development of arthrofibrosis. The effect of duration of immobilization was significant, with each extra day of immobilization increasing the odds of arthrofibrosis by 9% (OR 1.09, P=0.001).

Conclusions:

Duration of immobilization, fracture pattern, presence of deep postoperative infection, and energy of injury were all predictive factors for the development of elbow arthrofibrosis after operative treatment of intraarticular elbow fractures.
ABNORMAL RETINAL REFLECTIVITY TO SHORT-WAVELENGTH LIGHT IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA
Authors: Sallo Ferenc B. , Leung Irene , Zeimer Meike , Clemons Traci E. , Dubis Adam M. , Fruttiger Marcus , Pauleikhoff Daniel , Chew Emily Y. , Egan Catherine , Peto Tunde , Bird Alan C. ,   the MacTel Study Group
Published: June 2017

Purpose:

Macular telangiectasia Type 2 (MacTel) is a bilateral, progressive, potentially blinding retinal disease characterized by vascular and neurodegenerative signs, including an increased parafoveal reflectivity to blue light. Our aim was to investigate the relationship of this sign with other signs of macular telangiectasia Type 2 in multiple imaging modalities.

Methods:

Participants were selected from the MacTel Type 2 study, based on a confirmed diagnosis and the availability of images. The extent of signs in blue-light reflectance, fluorescein angiographic, optical coherence tomographic, and single- and dual-wavelength autofluorescence images were analyzed.

Results:

A well-defined abnormality of the perifovea is demonstrated by dual-wavelength autofluorescence and blue-light reflectance in early disease. The agreement in area size of the abnormalities in dual-wavelength autofluorescence and in blue-light reflectance images was excellent: for right eyes: ρ = 0.917 (P < 0.0001, 95% confidence interval 0.855–0.954, n = 46) and for left eyes: ρ = 0.952 (P < 0.0001, 95% confidence interval 0.916–0.973, n = 49). Other changes are less extensive initially and expand later to occupy that area and do not extend beyond it.

Conclusion:

Our findings indicate that abnormal metabolic handling of luteal pigment and physical changes giving rise to increased reflectance are widespread in the macula throughout the natural history of the disease, precede other changes, and are relevant to early diagnosis.
The rising prevalence of obesity: part B—public health policy solutions
Authors: Agha Maliha , Agha Riaz
Published: June 2017

Obesity is likely to supersede tobacco as the biggest cause of premature death. England has some of the worst figures and trends in obesity compared with the rest of the Europe. Rising obesity prevalence is an international crisis that has the potential to overwhelm health care resources as well as creating enormous human suffering and social cost. This article outlines potential public health policy solutions to this crisis.
A Rare Case of Pupillary Block Glaucoma Following CentraFLOW Implantable Collamer Lens Surgery
Authors: Grover Isha G. , Senthil Sirisha , Murthy Somasheila , Reddy Jagadesh C.
Published: June 2017

A 28-year-old lady with a refractive error of −11.0 D sphere/−1.50 D cylinder at 160 degrees in the right eye underwent an uneventful Implantable Collamer Lens surgery (ICL) with a V4c model, which uses a central Aquaport. This ICL does not require preoperative laser iridotomy or surgical iridectomy, as the centraflow opening is designed to prevent pupillary block. At postoperative day 1, her visual acuity in the right eye was 20/400, with diffuse microcystic corneal edema with fixed, dilated pupil and high intraocular pressure. Following intravenous mannitol, the corneal edema resolved. It was then noted that the ICL was anteriorly displaced, creating acute pupillary block, presumably due to obstruction of the central Aquaport with viscoelastic and inflammatory debris. She underwent AC wash the same day that helped in IOP control; however, the pupil remained permanently dilated and fixed because of extensive sphincter atrophy as a result of acute pupillary block. By 1 month, the visual acuity was 20/30 with an IOP of 14 mm Hg, which was maintained at 1-year follow-up. We report the first case of pupillary block glaucoma with this particular ICL design, suggesting the need for careful attention to complete removal of viscoelastic in the anterior chamber and behind the ICL, to prevent such complications and their cosmetically unacceptable sequelae.
Colistin Use in Neonates and Children With Infections Due to Carbapenem-resistant Bacteria
Authors: Antachopoulos Charalampos , Iosifidis Elias
Published: June 2017

Current evidence on the use of colistin in pediatric patients for infections caused by carbapenem-resistant bacteria is based on retrospective case series. The coadministration of colistin with other antimicrobial agents was associated with a relatively low rate of nephrotoxicity and a favorable outcome in >70% of these patients. Further study of colistin pharmacokinetics in children and neonates will likely lead to optimization of dosage recommendations.
CYP2E1 Gene Polymorphisms Related to the Formation of Coronary Artery Lesions in Kawasaki Disease
Authors: Chang Ling-Sai , Hsu Yu-Wen , Lu Chien-Chang , Lo Mao-Hung , Hsieh Kai-Sheng , Li Sung-Chou , Chang Wei-Chiao , Kuo Ho-Chang
Published: June 2017

Background:

Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients’ risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD.

Methods:

We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression.

Results:

The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types.

Conclusion:

This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.
First Detection of Chikungunya Virus in Breast Milk
Authors: Campos Gubio Soares , Albuquerque Bandeira Antonio Carlos , Diniz Rocha Verônica França , Dias Juarez Pereira , Carvalho Rejane Hughes , Sardi Silvia Ines
Published: June 2017

Chikungunya virus (CHIKV) has never been detected in human breast milk. This is a brief report of CHIKV infection in a breastfeeding woman of a 3-month-old baby. The mother’s CHIKV-RT PCR was positive in serum, urine and milk. The baby’s CHIKV serology and reverse transcription polimerase chain reaction (RT-PCR) were negative. The detection of CHIKV in milk raises clinical and epidemiologic questions.
Redistribution of Streptococcus pneumoniae Serotypes After Nationwide 13-valent Pneumococcal Conjugate Vaccine Program in Children in Northern Taiwan
Authors: Cho Ying-Chun , Chiu Nan-Chang , Lu Chun-Yi , Huang Daniel Tsung-Ning , Huang Fu-Yuan , Chang Luan-Yin , Huang Li-Min , Chi Hsin
Published: June 2017

Background:

After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy.

Methods:

S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients’ expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities.

Results:

Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%–10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P < 0.0001) but nonvaccine serotypes increased from 8.8% to 51.5% (P < 0.0001).

Conclusions:

The step-by-step PCV13 national immunization program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.
Ivermectin 1% Cream
Authors: Rasmussen Annelise , Jacob Sharon E.
Published: June 2017

A drug is defined as a substance that exerts a physiologic effect upon introduction to a biological system. These drugs may come in various forms including ingested pills, topical creams or ointments, and inhaled or injected substances. The purpose of this column is to bring attention to common drugs used in dermatology, their usage and purpose, their mechanisms, and available alternatives. This edition focuses on ivermectin and its usage in treatment of rosacea.
Comparison of Approaches for Notification and Authorization in Pragmatic Clinical Research Evaluating Commonly Used Medical Practices
Authors: Weinfurt Kevin P. , Bollinger Juli M. , Brelsford Kathleen M. , Bresciani Martina , Lampron Zachary , Lin Li , Topazian Rachel J. , Sugarman Jeremy
Published: June 2017

Background:

For pragmatic clinical research comparing commonly used treatments, questions exist about if and how to notify participants about it and secure their authorization for participation.

Objective:

To determine how patients react when they seek clinical care and encounter one of several different pragmatic clinical research studies.

Research Design:

In an online survey using a between-subjects experimental design, respondents read and responded to 1 of 24 hypothetical research scenarios reflecting different types of studies and approaches to notification and authorization (eg, general notification, oral consent, written consent).

Subjects:

English-speaking US adults 18 years and older.

Measures:

Willingness to participate in the hypothetical study, acceptability of the notification and authorization approach, understanding of the study, perceptions of benefit/harm, trust, and perception of amount of study information received.

Results:

Willingness to participate did not differ by notification and authorization approach. Some (21%–36%) of the patients randomized to general notification with an explicit opt-out provision were not aware they would be enrolled by default. Acceptability was greatest for and similar among notification and authorization approaches that actively engaged the patient (eg, oral or written consent) and lower for approaches with less engagement (eg, general notification). Problems of understanding were found among 20%–55% of respondents, depending on the particular scenario. Most respondents (77%–94%) felt that participation in the hypothetical study posed no risks of harm to their health or privacy.

Conclusions:

Current attitudes about notification and authorization approaches and difficulties understanding pragmatic clinical research pose significant challenges for pragmatic research. Data from this study provide a starting point to developing solutions to these surprisingly complex issues.
Thigh Ultrasound Monitoring Identifies Decreases in Quadriceps Femoris Thickness as a Frequent Observation in Critically Ill Children*
Authors: Valla Frederic V. , Young David K. , Rabilloud Muriel , Periasami Uvaraj , John Manoj , Baudin Florent , Vuillerot Carole , Portefaix Aurélie , White Deborah , Ridout Jenna A. , Meyer Rosan , Gaillard Le Roux Bénédicte , Javouhey Etienne , Pathan Nazima
Published: June 2017

Objectives:

Significant muscle wasting develops in critically ill adults, with subsequent worse outcomes. In the pediatric setting, occurrence and effects of muscle wasting are undescribed; this is in part due to a lack of validated, objective methods for assessing muscle wasting. A single measurement of quadriceps femoris thickness has failed to show consistent reproducibility. We hypothesized that averaging repeated measurements could afford good reproducibility to allow for quadriceps femoris thickness decline detection and monitoring.

Design:

A prospective bedside observational study.

Setting:

Two PICUs.

Patients:

Mechanically ventilated critically ill children were 15 years and younger.

Interventions:

Transverse and longitudinal axis measurements of quadriceps femoris anterior thickness were undertaken using bedside ultrasound. The average of four measurement values was recorded. The location of measurement was marked for consistency within subsequent measurements by the same or another trained operator, to assess intra- and interoperator repeatability and reproducibility of the technique. Where feasible, serial measurements were undertaken until the time of extubation in a group of children with prolonged PICU stay (> 5 d).

Measurements and Main Results:

Seventy-three children were enrolled to assess intra- and interoperator ultrasound reliability. Their median (25–75 interquartile range) age and weight were 30 months (4.5–96) and 10 kg (5–23.5). In the intraoperator repeatability study, mean relative difference in quadriceps femoris muscle thickness was 0.36% ± 2.5% (lower and upper limits of agreement: −4.5/+5.2%). In the interoperator reproducibility study, intraclass correlation coefficient was 0.998. In the 17 children monitored over their PICU stay, quadriceps femoris thickness significantly decreased at day 5 by 9.8% (p = 0.006) and by 13.3% (< 0.001) at the last performed measurement.

Conclusions:

Quadriceps femoris thickness decrease, proposed as a surrogate for muscle mass, is an early, frequent, and intense phenomenon in PICU. Quadriceps femoris ultrasonography is a reliable technique to monitor this process and in future could help to guide rehabilitation and nutrition interventions.
Brief Report: High Need to Switch cART or Comedication With the Initiation of DAAs in Elderly HIV/HCV-Coinfected Patients
Authors: Smolders Elise J. , Smit Colette , T. M. M. de Kanter Clara , Dofferiiof Anton S. M. , Arends Joop E. , Brinkman Kees , Rijnders Bart , van der Valk Marc , Reiss Peter , Burger David M. ,   on behalf the ATHENA national HIV observational cohort
Published: June 2017

Background:

To describe the use of nonantiretroviral comedication and combination antiretroviral therapy (cART) in patients coinfected with HIV/hepatitis C virus (HCV) and to predict the potential for drug–drug interactions (DDIs) with direct-acting antivirals (DAAs) against HCV.

Methods:

This is a retrospective, cross-sectional study, using the Dutch, nationwide ATHENA observational HIV cohort database. All patients with a known HIV/HCV coinfection on January 1, 2015, were included. Comedication and cART registered in the database were listed. The potential for DDIs between DAAs and comedication/cART were predicted using http://hep-druginteractions.org. DDIs were categorized as: (1) no clinically relevant DDI; (2) possible DDI; (3) contraindication; or (4) no information available.

Results:

We included 777 patients of whom 488 (63%) used nonantiretroviral comedication. At risk for a category 2/3 DDI with nonantiretroviral comedications were 299 patients (38%). Most DDIs were predicted with paritaprevir/ritonavir, ombitasvir ± dasabuvir (47% of the drugs) and least with grazoprevir/elbasvir (11% of the drugs). Concerning cART, daclatasvir/sofosbuvir is the most favorable combination as no cART is contraindicated with this combination. In genotype 1/4 patients, grazoprevir/elbasvir is least favorable as 75% of the patients must alter their cART.

Conclusions:

This study showed that comedication use in the aging HIV/HCV population is frequent and diverse. There is a high potential for DDIs between DAAs and comedication/cART.
Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years
Authors: Clifford Katherine M. , Samboju Vishal , Cobigo Yann , Milanini Benedetta , Marx Gabriel A. , Hellmuth Joanna M. , Rosen Howard J. , Kramer Joel H. , Allen Isabel E. , Valcour Victor G.
Published: June 2017

Background:

Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants.

Methods:

We examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24).

Results:

The mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status.

Conclusions:

Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.
Hepatic Venous Outflow Stenosis After Auxiliary Left Hemiliver Transplantation Diagnosed by Ultrasonic Shear Wave Elastography Combined With Doppler Ultrasonography
Authors: Li Jia-Wu , Lu Qiang , Luo Yan
Published: June 2017

Hepatic vein stenosis after liver transplantation is a relatively rare complication that could even result in graft loss. However, it is difficult to arrive at a definite diagnosis at the early stage of postoperation, and there are few researches on ultrasonic shear wave elastography in the diagnosis of hepatic vein stenosis. We report the case of an 11-year-old male patient with cirrhosis due to hepatolenticular degeneration who received an auxiliary left hemiliver graft from his uncle. Massive ascites developed in 4 days after the operation. Stenosis was suspected at the site of anastomosis by Doppler ultrasonography when elevating the velocity of the left hepatic vein. Meanwhile, increased stiffness of the graft was revealed by ultrasonic shear wave elastography. The stenosis was confirmed by subsequent digital subtraction angiography. Ascites decreased gradually after the stent implantation. Our case indicates that ultrasonic shear wave elastography combined with Doppler ultrasonography is a promising method for noninvasive diagnosis of hepatic venous outflow stenosis following liver transplantation.
The Volume-outcome Relationship in Deceased Donor Kidney Transplantation and Implications for Regionalization
Authors: Barbas Andrew S. , Dib Martin J. , Rege Aparna S. , Vikraman Deepak S. , Sudan Debra L. , Knechtle Stuart J. , Scarborough John E.
Published: June 2017

Objective:

The aim of this study was to investigate the volume-outcome relationship in kidney transplantation by examining graft and patient outcomes using standardized risk adjustment (observed-to-expected outcomes). A secondary objective was to examine the geographic proximity of low, medium, and high-volume kidney transplant centers in the United States.

Summary of Background Data:

The significant survival benefit of kidney transplantation in the context of a severe shortage of donor organs mandates strategies to optimize outcomes. Unlike for other solid organ transplants, the relationship between surgical volume and kidney transplant outcomes has not been clearly established.

Methods:

The Scientific Registry of Transplant Recipients was used to examine national outcomes for adults undergoing deceased donor kidney transplantation from January 1, 1999 to December 31, 2013 (15-year study period). Observed-to-expected rates of graft loss and patient death were compared for low, medium, and high-volume centers. The geographic proximity of low-volume centers to higher volume centers was determined to assess the impact of regionalization on patient travel burden.

Results:

A total of 206,179 procedures were analyzed. Compared with low-volume centers, high-volume centers had significantly lower observed-to-expected rates of 1-month graft loss (0.93 vs 1.18, P<0.001), 1-year graft loss (0.97 vs 1.12, P<0.001), 1-month patient death (0.90 vs 1.29, P=0.005), and 1-year patient death (0.95 vs 1.15, P=0.001). Low-volume centers were frequently in close proximity to higher volume centers, with a median distance of 7 miles (interquartile range: 2 to 75).

Conclusions:

A robust volume-outcome relationship was observed for deceased donor kidney transplantation, and low-volume centers are frequently in close proximity to higher volume centers. Increased regionalization could improve outcomes, but should be considered carefully in light of the potential negative impact on transplant volume and access to care.
Impact of Cold Ischemia Time in Kidney Transplants From Donation After Circulatory Death Donors
Authors: Kayler Liise , Yu Xia , Cortes Carlos , Lubetzky Michelle , Friedmann Patricia
Published: June 2017

Background

Deceased-donor kidneys are exposed to ischemic events from donor instability during the process of donation after circulatory death (DCD). Clinicians may be reluctant to transplant DCD kidneys with prolonged cold ischemia time (CIT) for fear of an additional deleterious effect.

Methods

We performed a retrospective cohort study examining US registry data between 1998 and 2013 of adult first-time kidney-only recipients of paired kidneys (derived from the same donor transplanted into different recipients) from DCD donors.

Results

On multivariable analysis, death-censored graft survival (DCGS) was comparable between recipients of kidneys with higher CIT relative to paired donor recipients with lower CIT when the CIT difference was 1 hour or longer (adjusted hazard ratio, [aHR], 1.02; 95% confidence interval [CI], 0.88-1.17; n = 6276), 5 hours or longer (aHR, 0.98; 95% CI, 0.80-1.19; n = 3130), 10 hours or longer (aHR, 1.15; 95% CI, 0.82-1.60; n = 1124) or 15 hours (aHR, 1.15; 95% CI, 0.66-1.99; n = 498). There was a higher rate of primary non function in the long CIT groups for delta 1 hour or longer (0.89% vs 1.63%; P = 0.006), 5 hours (1.09% vs 1.67%, P = 0.13); 10 hours (0.53% vs 1.78%; P = 0.03), and 15 hours (0.40% vs 1.61%; P = 0.18), respectively. Between each of the 4 delta CIT levels of shorter and longer CIT, there was a significantly and incrementally higher rate of delayed graft function in the long CIT groups for delta 1 hour or longer (37.3% vs 41.7%; P < 0.001), 5 hours (35.9% vs 42.7%; P < 0.001), 10 hours (29.4% vs 44.2%, P < 0.001), and 15 hours (29.6% vs 46.1%, P < 0.001), respectively. Overall patient survival was comparable with delta CITs of 1 hour or longer (aHR, 0.96; 95% CI, 0.84-1.08), 5 hours (aHR, 1.01; 95% CI, 0.85-1.20), and 15 hours (aHR, 1.27; 95% CI, 0.79-2.06) but not 10 hours (aHR, 1.47; 95% CI, 1.09-1.98).

Conclusions

These results suggest that in the setting of a prior ischemic donor event, prolonged CIT has limited bearing on long-term outcomes.
Informatics for Cancer Immunotherapy
Authors: Hammerbacher J. , Snyder A.
Published: June 2017

The rapid development of immunomodulatory cancer therapies has led to a concurrent increase in the application of informatics techniques to the analysis of tumors, the tumor microenvironment, and measures of systemic immunity. In this review, the use of tumors to gather genetic and expression data will first be explored. Next, techniques to assess tumor immunity are reviewed, including HLA status, predicted neoantigens, immune microenvironment deconvolution and T-cell receptor (TCR) sequencing. Attempts to integrate these data are in early stages of development and are discussed next. Finally, we review the application of these informatics strategies to therapy development, with a focus on vaccines, adoptive cell transfer, and checkpoint blockade therapies.
Resting-State fMRI Dynamics and Null Models: Perspectives, Sampling Variability, and Simulations
Authors: Miller Robyn , Abrol Anees , Adali Tulay , Levin-Schwarz Yuri , Calhoun Vince
Published: June 2017

Studies of resting state functional MRI (rs-fRMI) are increasingly focused on “dynamics”, or on those properties of brain activation that manifest and vary on timescales shorter than the scan’s full duration. This shift in focus has led to a flurry of interest in developing hypothesis testing frameworks and null models applicable to the dynamical setting. Thus far however, these efforts have been weakened by a number of crucial shortcomings that are outlined and discussed in this short paper. We focus here on aspects of recently proposed null models that, we argue, are poorly formulated relative to the hypotheses they are designed to test, i.e. their potential role in separating functionally relevant BOLD signal dynamics from noise or intermittent background and maintenance type processes is limited by factors that are fundamental rather than merely quantitative or parametric. In this short position paper, we emphasize that (1) serious care must be exercised in building null models for rs-fMRI dynamics from distributionally stationary univariate or multivariate timeseries, i.e. timeseries whose values are each independently drawn from one pre-specified probability distribution; and (2) measures such as kurtosis that quantify over-concentration of observed values in the far tails of some reference distribution may not be particularly suitable for capturing signal features most plausibly contributing to functionally relevant brain dynamics. Other metrics targeted, for example, at capturing the epochal temporal variation that contributes heavily to dynamic functional connectivity estimates and is and often taken as a signature of brain responsiveness to stimuli or experimental tasks, could play a more scientifically clarifying role. As we learn more about the phenomenon of functionally relevant brain dynamics and its imaging correlates, scientifically meaningful null hypotheses and well-tuned null models will naturally emerge. We also revisit the important concept of distributional stationarity, discuss how it manifests within realizations versus across multiple realizations, and provide guidance on the benefits and limitations of employing this type of stationarity in modeling the absence or functionally relevant temporal dynamics in resting state fMRI. We hope that the discussions herein are useful, and promote thoughtful consideration of these important issues.
Variable precision in visual perception
Authors: Shen Shan , Ma Wei Ji
Published: June 2017

Given the same sensory stimuli in the same task, human observers do not always make the same response. Well-known sources of behavioral variability are sensory noise and guessing. Visual short-term memory studies have suggested that the precision of the sensory noise is itself variable. However, it is unknown whether precision is also variable in perceptual tasks without a memory component. We searched for evidence for variable precision in 11 visual perception tasks with a single relevant feature, orientation. We specifically examined the effect of distractor stimuli: distractors were absent, homogeneous and fixed across trials, homogeneous and variable, or heterogeneous and variable. We first considered four models: with and without guessing, and with and without variability in precision. We quantified the importance of both factors using six metrics: factor knock-in difference, factor knock-out difference, and log factor posterior ratio, each based on AIC or BIC. According to all six metrics, we found strong evidence for variable precision in five experiments. Next, we extended our model space to include potential confounding factors: the oblique effect and decision noise. This left strong evidence for variable precision in only one experiment, in which distractors were homogeneous but variable. Finally, when we considered suboptimal decision rules, the evidence also disappeared in this experiment. Our results provide little evidence for variable precision overall and only a hint when distractors are variable. Methodologically, the results underline the importance of including multiple factors in factorial model comparison: testing for only two factors would have yielded an incorrect conclusion.