bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Life in Rectal Cancer Patients After Chemoradiation: Watch-and-Wait Policy Versus Standard Resection – A Matched-Controlled Study
Authors: Hupkens Britt J.P. , Martens Milou H. , Stoot Jan H. , Berbee Maaike , Melenhorst Jarno , Beets-Tan Regina G. , Beets Geerard L. , Breukink Stéphanie O.
Published: September 2017

BACKGROUND:

Fifteen to twenty percent of patients with locally advanced rectal cancer have a clinical complete response after chemoradiation therapy. These patients can be offered nonoperative organ-preserving treatment, the so-called watch-and-wait policy. The main goal of this watch-and-wait policy is an anticipated improved quality of life and functional outcome in comparison with a total mesorectal excision, while maintaining a good oncological outcome.

OBJECTIVE:

The aim of this study was to compare the quality of life of watch-and-wait patients with a matched-controlled group of patients who underwent chemoradiation and surgery (total mesorectal excision group).

DESIGN:

This was a matched controlled study.

SETTINGS:

This study was conducted at multiple centers.

PATIENTS:

The study population consisted of 2 groups: 41 patients after a watch-and-wait policy and 41 matched patients after chemoradiation and surgery. Patients were matched on sex, age, tumor stage, and tumor height. All patients were disease free at the moment of recruitment after a minimal follow-up of 2 years.

MAIN OUTCOME MEASURES:

Quality of life was measured by validated questionnaires covering general quality of life (Short Form 36, European Organization for Research and Treatment of Cancer QLQ-C30), disease-specific total mesorectal excision (European Organization for Research and Treatment of Cancer QLQ-CR38), defecation problems (Vaizey and low anterior resection syndrome scores), sexual problems (International Index of Erectile Function and Female Sexual Function Index), and urinary dysfunction (International Prostate Symptom Score).

RESULTS:

The watch-and-wait group showed better physical and cognitive function, better physical and emotional roles, and better global health status compared with the total mesorectal excision group. The watch-and-wait patients showed fewer problems with defecation and sexual and urinary tract function.

LIMITATIONS:

This study only focused on watch-and-wait patients who achieved a sustained complete response for 2 years. In addition, this is a study with a limited number of patients and with quality-of-life measurements on nonpredefined and variable intervals after surgery.

CONCLUSIONS:

After a successful watch-and-wait approach, the quality of life was better than after chemoradiation and surgery on several domains. However, chemoradiation therapy on its own is not without long-term side effects, because one-third of the watch-and-wait patients experienced major low anterior resection syndrome symptoms, compared with 66.7% of the patients in the total mesorectal excision group. SeeVideo Abstractat http://links.lww.com/DCR/A395.
Condyloma Acuminatum, Anal Intraepithelial Neoplasia, and Anal Cancer in the Setting of HIV: Do We Really Understand the Risk?
Authors: Fazendin Edward A. , Crean Alexander J. , Fazendin Jessica M. , Kucejko Robert J. , Gill Harkenwar S. , Poggio Juan L. , Stein David E.
Published: September 2017

BACKGROUND:

The gold standard for surveillance of patients with anal lesions is unclear.

OBJECTIVE:

The aim of this study was to stratify patients for risk of progression of disease and to determine appropriate intervals for surveillance of patients with anal disease.

DESIGN:

This was a retrospective chart review for patients treated for anal lesions between 2007 and 2014. Only patients with ≥1 year of follow-up from index evaluation, pathology, documented physical examination, and anoscopy findings were included for analysis.

SETTINGS:

The study was conducted at an urban university hospital.

PATIENTS:

HIV-positive patients with anal lesions treated with excision and fulguration were included.

MAIN OUTCOME MEASURES:

Recurrence of anal lesions, progression of disease, and progression to cancer were measured.

RESULTS:

Ninety-one patients met inclusion criteria. The mean age was 41.6 years, and mean follow-up was 38.6 months (range, 11.0–106.0 mo). On initial pathology, 8 patients (8.8%) had a diagnosis of condyloma acuminatum without dysplasia, 20 patients (22%) had anal intraepithelial neoplasia I, 32 (35.2%) had anal intraepithelial neoplasia II, and 31 (34.1%) had anal intraepithelial neoplasia III. Sixty-nine patients (75.8%) had repeat procedures. Seven (87.5%) of 8 patients with condyloma and 6 (30%) of 20 patients with anal intraepithelial neoplasia I progressed to high-grade lesions. Five (15.6%) of 32 patients progressed from anal intraepithelial neoplasia II to III, and 2 patients with anal intraepithelial neoplasia III (6.5%) developed squamous cell carcinoma (2.3% for the entire cohort).

LIMITATIONS:

This was a single institution study. High-resolution anoscopy was not used.

CONCLUSIONS:

All of the HIV-positive patients with condyloma or anal intraepithelial neoplasia, regardless of the presence of dysplasia, should be surveyed at equivalent 3-month time intervals, because their risk of progression of disease is high. Video Abstract at http://links.lww.com/DCR/A389.
Transanal Total Mesorectal Excision: Pneumodissection of Retroperitoneal Structures Eases Laparoscopic Rectal Resection
Authors: Hüscher Cristiano G.S. , Lirici Marco Maria
Published: September 2017

INTRODUCTION:

Laparoscopic total mesorectal excision is effective and safe but often technically challenging because of inadequate exposure. Transanal total mesorectal excision was introduced to mitigate this limitation and improve the quality of mesorectal dissection in even the most challenging cases. Currently, the technique for transanal total mesorectal excision dissection is not standardized.

TECHNIQUE:

The sequential approach to transanal total mesorectal excision mirrors the principles of the transanal abdominal transanal procedure. It begins with the transanal step, followed by the laparoscopic step, and then the transanal total mesorectal excision. The perirectal space is entered via a full-thickness dissection of the anterior rectal wall. Carbon dioxide is left flowing, widening the embryonic planes between the mesorectal and pelvic fascias, then moving upward through the retroperitoneal space. The surgeon switches to the abdominal field and begins laparoscopic dissection, consisting of inferior mesenteric artery dissection and division, inferior mesenteric vein dissection and division, and possible splenic flexure dissection. Pneumodissection facilitates this procedure by distancing the inferior mesenteric artery from the hypogastric nerves and opening the embryonic fusion plane between the Toldt and Gerota fascias to allow faster division of the left colon lateral attachments. The operation continues with a switch to the perineal field and mesorectal excision.

RESULTS:

A total of 102 patients underwent transanal total mesorectal excision as described. Mean operative time was 185.0 + 87.5 minutes (range, 60–480 min), and there was no conversion to open surgery. Postoperative morbidity was 33.3%. Mortality rate at 30 days was 1.96% (2 cases). Quality of mesorectal excision according to Quirke was assessed in all of the specimens and found to be complete in 99 cases (97.1%) and nearly complete in 2.9% of cases.

CONCLUSIONS:

Transanal total mesorectal excision may benefit from pneumodissection, expedites the laparoscopic step, and the sequential approach facilitates the visualization of the correct dissection planes. The safety and cost-effectiveness of the procedure still warrant consideration. See Video at http://links.lww.com/DCR/A418.
YouTube Videos on Botulinum Toxin A for Wrinkles: A Useful Resource for Patient Education
Authors: Wong Katharine , Doong Judy , Trang Trinh , Joo Sarah , Chien Anna L.
Published: September 2017

BACKGROUND

Patients interested in botulinum toxin type A (BTX-A) for wrinkles search for videos on YouTube, but little is known about the quality and reliability of the content.

OBJECTIVE

The authors examined the quality, reliability, content, and target audience of YouTube videos on BTX for wrinkles.

MATERIALS AND METHODS

In this cross-sectional study, the term “Botox” was searched on YouTube. Sixty relevant videos in English were independently categorized by 2 reviewers as useful informational, misleading informational, useful patient view, or misleading patient view. Disagreements were settled by a third reviewer. Videos were rated on the Global Quality Scale (GQS) (1 = poor, 5 = excellent).

RESULTS

Sixty-three percent of the BTX YouTube videos were useful informational (GQS = 4.4 ± 0.7), 33% as useful patient view (GQS = 3.21 ± 1.2), 2% as misleading informational (GQS = 1), and 2% as misleading patient view (GQS = 2.5).

CONCLUSION

The large number of useful videos, high reliability, and the wide range of content covered suggests that those who search for antiwrinkle BTX videos on YouTube are likely to view high-quality content. This suggests that YouTube may be a good source of videos to recommend for patients interested in BTX.
A-101, a Proprietary Topical Formulation of High-Concentration Hydrogen Peroxide Solution: A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of the Dose–Response Profile in Subjects With Seborrheic Keratosis of the Face
Authors: DuBois Janet C. , Jarratt Michael , Beger Brian B. , Bradshaw Mark , Powala Christopher V. , Shanler Stuart D.
Published: September 2017

BACKGROUND

Seborrheic keratosis (SK) is a common benign skin tumor, yet no topical treatments are approved in the United States.

OBJECTIVE

To evaluate the proprietary, stabilized, high-concentration hydrogen peroxide–based topical solution A-101 (32.5% and 40% concentrations) for treatment of facial SK lesions.

MATERIALS AND METHODS

In this multicenter, double-blind, vehicle-controlled study, eligible subjects were randomly assigned to receive up to 2 treatments of A-101 40%, A-101 32.5%, or vehicle solution applied to a single facial SK lesion. The primary efficacy assessment was the Physician's Lesion Assessment (PLA), a validated 4-ordinal scale.

RESULTS

The primary end point, the mean reduction in PLA grade from baseline to Day 106 was 1.7 for A-101 40%, 1.4 for A-101 32.5%, and 0.1 for vehicle (p < .001, both concentrations vs vehicle). Lesions for 68%, 62%, and 5% of subjects, respectively, were judged to be clear or near clear (p < .001, both concentrations vs vehicle). Local skin reactions were predominantly mild and transient. No subjects discontinued because of treatment-related adverse events.

CONCLUSION

A-101 solution demonstrated efficacy in treating SKs on the face. Greater magnitude of effect was seen with the 40% concentration than the 32.5% concentration. A-101 solution had a favorable safety and tolerability profile at both concentrations.
Clinical and Histological Evaluations of Enlarged Facial Skin Pores After Low Energy Level Treatments With Fractional Carbon Dioxide Laser in Korean Patients
Authors: Kwon Hyuck Hoon , Choi Sun Chul , Lee Won-Yong , Jung Jae Yoon , Park Gyeong-Hun
Published: September 2017

BACKGROUND

Enlarged facial pores can be an early manifestation of skin aging and they are a common aesthetic concern for Asians. However, studies of improving the appearance of enlarged pores have been limited.

OBJECTIVE

The authors aimed to study the application of CO2 fractional laser treatment in patients with enlarged facial pores.

METHODS

A total of 32 patients with dilated facial pores completed 3 consecutive sessions of low energy level treatments with a fractional CO2 laser at 4-week intervals. Image analysis was performed to calculate the number of enlarged pores before each treatment session and 12 weeks after the final treatment.

RESULTS

After application of laser treatments, there was a significant decrease in the number of enlarged pores. The mean number of enlarged pores was decreased by 28.8% after the second session and by 54.5% at post-treatment evaluation. Post-treatment side effects were mild and transitory. Histological and immunohistochemical analyses demonstrated clear increases in the number of collagen fibers and the expression of transforming growth factor–β1.

CONCLUSION

The short-term results showed that treatment with low energy level CO2 fractional laser therapy could be a safe and effective option for patients with Fitzpatrick skin Types III and IV who are concerned with enlarged pores.
RETINAL MICROVASCULATURE AND VISUAL ACUITY AFTER INTRAVITREAL AFLIBERCEPT IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION
Authors: Winegarner Andrew , Wakabayashi Taku , Hara-Ueno Chikako , Sato Tatsuhiko , Busch Caleb , Fukushima Yoko , Sayanagi Kaori , Nishida Kentaro , Sakaguchi Hirokazu , Nishida Kohji
Published: September 2017

Purpose:

To investigate vascular perfusion and foveal avascular zone area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) after intravitreal aflibercept therapy in central retinal vein occlusion eyes and their association with best-corrected visual acuity.

Methods:

Thirty-five subjects with central retinal vein occlusion and macular edema were evaluated. After macular edema resolution following intravitreal aflibercept, subjects underwent optical coherence tomography angiography to measure SCP and DCP perfusion and the foveal avascular zone within a 3 × 3-mm area. Correlations between best-corrected visual acuity and optical coherence tomography angiography measurements were examined.

Results:

After intravitreal aflibercept therapy, mean retinal vascular area was 3.41 ± 0.74 mm2 in the SCP and 3.25 ± 0.91 mm2 in the DCP. Foveal avascular zone area was 1.03 ± 1.04 mm2 in the SCP and 1.78 ± 1.73 mm2 in the DCP. Improved best-corrected visual acuity was significantly associated with better SCP and DCP perfusion (both P < 0.001) and with smaller SCP and DCP foveal avascular zone areas (both P < 0.001). Additionally, SCP and DCP perfusion were negatively correlated with macular edema before treatment (P < 0.05) and ischemia (determined via pretreatment fluorescein angiography, P < 0.05), and positively correlated with photoreceptor integrity (P < 0.001).

Conclusion:

Patients with better retinal perfusion and less retinal ischemia are associated with better visual outcomes after aflibercept in eyes with central retinal vein occlusion.
DETECTION OF TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Ahmed Daniel , Stattin Martin , Graf Alexandra , Forster Julia , Glittenberg Carl , Krebs Ilse , Ansari-Shahrezaei Siamak
Published: September 2017

Purpose:

To compare the detection rate of choroidal neovascularization (CNV) in treatment-naive neovascular age-related macular degeneration by swept source optical coherence tomography angiography (SS-OCTA, Topcon's DRI Triton) working at 1,050 nm wavelength versus fluorescence angiography.

Methods:

Cross-sectional analysis of 156 eyes (107 neovascular age-related macular degeneration and 49 dry AMD) in 98 patients, previously diagnosed by multimodal imaging using fluorescein (FA) and indocyanine green angiography (Heidelberg's Spectralis) in a tertiary retina center, evaluated by SS-OCTA 4.5 mm × 4.5 mm and 6 mm × 6 mm macular cubes. Main outcome measures were sensitivity and specificity of SS-OCTA in AMD. Potential factors influencing CNV detection rate were analyzed.

Results:

Swept source optical coherence tomography angiography detected CNV in 81 of 107 eyes, resulting in a sensitivity of 75.7%. In 49 eyes with dry AMD, no CNV could be identified (specificity 100%). A statistical significance was calculated for nondetection of treatment-naive CNV by SS-OCTA in pigment epithelial detachment over 400 μm (P = 0.0238).

Conclusion:

Topcon's SS-OCTA was not able to detect all CNV lesions. Large pigment epithelial detachments were associated with signal loss. Fluorescence angiography still remains the gold standard, but the tested SS-OCTA device can be considered as a feasible additional diagnostic tool in AMD.
ASSOCIATIONS BETWEEN INDIVIDUAL RETINAL LAYER THICKNESSES AND DIABETIC PERIPHERAL NEUROPATHY USING RETINAL LAYER SEGMENTATION ANALYSIS
Authors: Kim Jin Hyung , Lee Min Woo , Byeon Suk Ho , Kim Sung Soo , Koh Hyoung Jun , Lee Sung Chul , Kim Min
Published: September 2017

Purpose:

To evaluate clinical correlations between the thicknesses of individual retinal layers in the foveal area of diabetic patients and the presence of diabetic peripheral neuropathy (DPN).

Methods:

This retrospective, observational, cross-sectional study enrolled a total of 120 eyes from 120 patients. The eyes were divided into 3 groups: normal controls (n = 42 eyes), patients with diabetes mellitus (n = 42 eyes) but no DPN, and patients with diabetes mellitus and DPN (n = 36 eyes). The primary outcome measures were the thickness of all retinal layers in the central 1-mm zone measured using the segmentation analysis of spectral-domain optical coherence tomography. Correlations between the thicknesses of the individual retinal layers and the presence of DPN were also analyzed. Logistic regression analyses were used to determine which change in layer thickness had the most significant association with the presence of DPN.

Results:

The mean thicknesses and the ratios of retinal nerve fiber layers to total retina thicknesses in the DPN group were 10.77 ± 1.79 μm and 4.10 ± 0.55%, which was significantly lower than those in normal controls and the diabetes mellitus with no DPN group (P = 0.014 and P = 0.001, respectively). Logistic regression analyses also showed that the decrease in thicknesses of the retinal nerve fiber layers and the inner nuclear layer are significant factors for predicting a higher risk for DPN development (odds ratio = 7.407 and 1.757; P < 0.001 and P = 0.001, respectively).

Conclusion:

A decrease in the retinal nerve fiber layer and the inner nuclear layer thickness was significantly associated with the presence of DPN.
Genetic Polymorphisms of Manganese-Dependent Superoxide Dismutase in Chagas Disease
Authors: Lassen Oscar , Tabares Sandra , Ojeda Silvia , Dotto Gladys , Bertolotto Patricia , Sembaj Adela
Published: September 2017

Background

Infection with Trypanosoma cruzi triggers inflammatory mechanisms and induces the activity of manganese-dependent superoxide dismutase. Genetic single-nucleotide polymorphisms of this enzyme generate proteins with reduced enzymatic activity. The aims of this study were to determine the frequency of the polymorphisms Ala-9Val and Ile58Thr of the manganese-dependent superoxide dismutase gene in DNA from chagasic and nonchagasic patients and to establish a relationship between these polymorphisms with chronic chagasic cardiomyopathy.

Methods

Two hundred fifty-eight unrelated patients underwent a general clinical examination and an electrocardiogram, a chest radiograph, and a 12-lead color Doppler echocardiogram were taken. Besides, we evaluate liver and renal function, lipid profile, and diagnosis of Chagas disease and genetic polymorphisms by polymerase chain reaction–restriction fragment length polymorphism. The patients were classified as nonchagasic group with negative serology for Chagas disease and the chagasic group with positive serology. This group was subdivided into asymptomatic when patients did not present abnormal cardiac symptoms and symptomatic if the chest radiograph, electrocardiogram, and/or color Doppler echocardiogram showed some alteration.

Results

The female chagasic population shows a high frequency of the ile58ile genotype (P = 0.010; odds ratio, 3.3; 95% confidence interval, 1.35–8.38). Lower frequency of the ala-9ala genotype was detected in symptomatic Chagas patients (P = 0.001; odds ratio, 3.147; 95% confidence interval, 1.39–7.482). The analysis revealed an interaction between the ala/ala + val/val genotype (P = 0.0108) with the plasma concentration of low-density lipoprotein cholesterol in the symptomatic Chagas group.

Conclusions

Our results show that the presence of the val allele is associated with chronic chagasic cardiomyopathy. The prognostic value of these results should be more deeply investigated.
Reliability of an Installed Chair Exit Alarm System for Fall Prevention: A Double-Blind Randomized Controlled Trial
Authors: Li Tianfu , Wilson Christopher M. , Basal Yasmeen
Published: September 2017

Introduction and Background:

Within the acute care hospital setting, falls and fall prevention are a common concern among clinical staff as significant time and resources are dedicated to fall prevention. Chair alarm systems are commonly used; however, they can increase costs and may also contribute to alarm fatigue via overly sensitive systems.

Purpose:

To compare the reliability and accuracy of an installed chair alarm system with a timer (developed by the principal investigator), titled Safe Sitting System, as compared with 2 commercially available and commonly used products: (1) a single-patient use pressure-sensing alarm system (primary control) and (2) a magnetic clip-on alarm (secondary control).

Design:

Single-center double-blind randomized controlled trial using a within-subject design.

Subjects:

Seventy-five healthy volunteers 19 to 60 years of age.

Intervention:

Blinded subjects performed a series of 9 common motions in 2 chairs—one that contained the primary control product and the second with the Safe Sitting System. Which chair was tested first was randomized and a magnetic clip-on alarm was used in both trials. A blinded data collector recorded whether either alarm was activated or not during each motion.

Results:

The Safe Sitting System chair had a total of 16 false positives out of all 600 responses (2.7%) and 0 false negatives out of 75 responses. The primary control product had a total of 187 false positives out of all 600 responses (31.2%) and 6 false negatives out of 75 responses (8.0%). The number of appropriate responses between the chairs was determined to be statistically significantly different as assessed by a sign test (P < .0001).

Conclusions:

An installed chair alarm with a timer and a slight delay in alarm response significantly reduced false positives and false negatives, which has the potential to reduce falls and improve patient safety during hospitalization. In addition, there is the potential for cost savings from an installed chair alarm system as compared with a single-patient use chair alarm.
Switching from reference infliximab to CT-P13 in patients with inflammatory bowel disease: 12 months results
Authors: Argüelles-Arias Federico , Guerra Veloz Maria Fernanda , Perea Amarillo Raul , Vilches-Arenas Angel , Castro Laria Luisa , Maldonado Pérez Belen , Chaaro Benallal Dina , Benítez Roldán Antonio , Merino Vicente , Ramirez Gabriel , Calleja-Hernández Miguel Angel , Caunedo Álvarez Angel , Romero Gómez Manuel
Published: September 2017

Background

Biological agents, such as infliximab, have transformed the outcomes of patients with immune-mediated inflammatory diseases. The advent of biosimilar treatment options such as CT-P13 promises to improve the availability of biological therapy, yet real-world switching data are currently limited. Here, we assess the effectiveness and safety of switching to CT-P13 from infliximab reference product (RP) in patients with inflammatory bowel disease.

Materials and methods

This was a prospective single-center observational study in patients with moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade) to CT-P13 treatment and followed up for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 3-monthly intervals, according to the Harvey–Bradshaw score and partial Mayo score for patients with CD and UC, respectively. C-reactive protein (CRP) was also measured. Adverse events were monitored and recorded throughout the study.

Results

A total of 98 patients with inflammatory bowel disease (67 CD/31 UC) were included. A total of 83.6% (56/67) of patients with CD were in remission at the time of the switch and 62.7% were in remission at 12 months. The Harvey–Bradshaw score showed a significant change at 12 months (P=0.007) but no significant change was observed in median CRP at this timepoint (P=0.364). A total of 80.6% (25/31) of patients with UC were in remission at the time of the switch and 65.3% (18/28) were in remission at 12 months. No significant changes in the median partial Mayo score (P=0.058) or CRP (P=0.329) were observed at 12 months. Serious adverse events related to medication were reported in 11 (11.2%) patients.

Conclusion

Switching from infliximab RP to CT-P13 is efficacious and well tolerated in patients with CD or UC for up to 12 months.
Squamous Cell Carcinoma With Hyper-IgE Syndrome: A Case Report
Authors: Sasihuseyinoglu Ayse S. , Yilmaz Mustafa , Altintaş Derya U. , Dogruel Dilek , Serbes Mahir , Uğuz Aysun H. , Kiroğlu Mete
Published: September 2017

Background:

Hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disease characterized by recurrent infections and elevated levels of serum immunoglobulin E, usually over 2000 IU/mL. Recurrent and chronic infection of the epidermis and squamous epithelium may also be a cause of squamous cell carcinoma (SCC). SCC is rare with HIES.

Case Report:

A 17-year-old male patient who was diagnosed as HIES was admitted with purulent right ear discharge. The patient had a history of eczema starting from the age of 7 months and a history of recurrent middle ear infection starting from the age of 5. Biopsy specimens were taken from the lesion in the external auditory canal, and the lesion was reported as SCC.

Conslusion:

Patients with autosomal recessive HIES are at an increased risk for infections and malignancies. SCC should be considered in the differential diagnosis of the patients presenting with recurrent middle ear infections and immunodeficiency.
A Patient Information Leaflet Reduces Parental Anxiety Before Their Child's First Craniofacial Multidisciplinary Outpatient Appointment
Authors: Pidgeon Thomas Edward , Blore Christopher David , Webb Yasmin , Horton Jo , Evans Martin
Published: September 2017

Introduction:

It is expected that a child's first outpatient appointment with a craniofacial multidisciplinary team (MDT) instills anxiety in parents. Limited data exist on the aspects of the appointment that parents are most concerned about and what information they desire. The effect of written information provision on this cohort is unstudied.

Methods:

Parents attending their child's first outpatient appointment with the Birmingham Children's Hospital Craniofacial MDT between September and December 2012 completed a questionnaire to identify concerns they had relating to the appointment. A patient information leaflet was subsequently developed and distributed. From September 2015 to January 2016, questionnaires completed by parents assessed the usefulness of the leaflet and whether it reduced parental anxiety.

Results:

Twenty-six initial questionnaires were returned. Seventeen respondents (65%) reported that they were concerned about some aspect of their child's appointment. Twenty-two (86%) expressed a desire for more information surrounding their child's appointment. Thirteen (50%) requested for this information to be provided using a patient information leaflet. After the introduction of the leaflet, 30 questionnaires were returned. All 30 (100.0%) found the leaflet easy to understand. Twenty-nine (96.7%) felt the leaflet provided helpful information. Eighteen (60.0%) felt less worried about the appointment after reading the leaflet.

Conclusions:

The majority of parents of children referred to a craniofacial MDT appointment displayed concerns that related to the appointment itself. Specific information relating to the appointment process itself was desired. A purpose-built leaflet successfully provided parents with desired information and lowered anxiety among the majority of attendees.
Effect modification ofFADS2polymorphisms on the association between breastfeeding and intelligence: results from a collaborative meta-analysis
Authors: Hartwig Fernando Pires , Davies Neil Martin , Horta Bernardo Lessa , Ahluwalia Tarunveer S. , Bisgaard Hans , Bønnelykke Klaus , Caspi Avshalom , Moffitt Terrie E. , Poulton Richie , Sajjad Ayesha , Tiemeier Henning W , Bueno Albert Dalmau , Guxens Mònica , Pineda Mariona Bustamante , Santa-Marina Loreto , Parker Nadine , Paus Tomáš , Pausova Zdenka , Lauritzen Lotte , Schnurr Theresia M. , Michaelsen Kim F. , Hansen Torben , Oddy Wendy , Pennell Craig E. , Warrington Nicole M. , Smith George Davey , Victora Cesar Gomes
Published: September 2017

Background

Accumulating evidence suggests that breastfeeding benefits the children’s intelligence. Long-chain polyunsaturated fatty acids (LC-PUFAs) present in breast milk may explain part of this association. Under a nutritional adequacy hypothesis, an interaction between breastfeeding and genetic variants associated with endogenous LC-PUFAs synthesis might be expected. However, the literature on this topic is controversial.

Methods and Findings

We investigated this Gene×Environment interaction in ade novometa-analysis involving >12,000 individuals in the primary analysis, and >45,000 individuals in a secondary analysis using relaxed inclusion criteria. Our primary analysis used ever breastfeeding,FADS2polymorphisms rs174575 and rs1535 coded assuming a recessive effect of the G allele, and intelligence quotient (IQ) in Z scores. Using random effects meta-analysis, ever breastfeeding was associated with 0.17 (95% CI: 0.03; 0.32) higher Z scores in IQ, or about 2.1 points. There was no strong evidence of interaction, with pooled covariate-adjusted interaction coefficients (i.e., difference between genetic groups of the difference in IQZ scores comparing ever with never breastfed individuals) of 0.12 (95% CI: −0.19; 0.43) and 0.06 (95% CI: −0.16; 0.27) for the rs174575 and rs1535 variants, respectively. Secondary analyses corroborated these results. In studies with >5.85 and <5.85 months of breastfeeding duration, pooled estimates for the rs174575 variant were 0.50 (95% CI: −0.06; 1.06) and 0.14 (95% CI: −0.10; 0.38), respectively, and 0.27 (95% CI: −0.28; 0.82) and −0.01 (95% CI: −0.19; 0.16) for the rs1535 variant. However, between-group comparisons were underpowered.

Conclusions

Our findings do not support an interaction between ever breastfeeding andFADS2polymorphisms. However, our subgroup analysis raises the possibility that breastfeeding supplies LC-PUFAs requirements for cognitive development (if such threshold exists) if it lasts for some (currently unknown) time. Future studies in large individual-level datasets would allow properly powered subgroup analyses and would improve our understanding on the role of breastfeeding duration in the breastfeeding×FADS2interaction.
Indirect assortative mating for human disease and longevity
Authors: Rawlik Konrad , Canela-Xandri Oriol , Tenesa Albert
Published: September 2017

Phenotypic correlations of couples for phenotypes evident at the time of mate choice, like height, are well documented. Similarly, phenotypic correlations among partners for traits not directly observable at the time of mate choice, like longevity or late-onset disease status, have been reported. Partner correlations for longevity and late-onset disease are comparable in magnitude to correlations in 1stdegree relatives. These correlations could arise as a consequence of convergence after mate choice, due to initial assortment on observable correlates of one or more risk factors (e.g. BMI), referred to as indirect assortative mating, or both. Using couples from the UK Biobank cohort, we show that longevity and disease history of the parents of white British couples is correlated. The correlations in parental longevity are replicated in the FamiLinx cohort. These correlations exceed what would be expected due to variations in lifespan based on year and location of birth. This suggests the presence of assortment on factors correlated with disease and lifespan, which show correlations across generations. Birth year, birth location, Townsend Deprivation Index, height, waist to hip ratio, BMI and smoking history of UK Biobank couples explained ~70% of the couple correlation in parental lifespan. For cardiovascular diseases, in particular hypertension, we find significant correlations in genetic values among partners, which support a model where partners assort for risk factors genetically correlated with cardiovascular disease. Identifying the factors that mediate indirect assortment on longevity and human disease risk will help to unravel what factors affect human disease and ultimately longevity.
Dynamic patterns of cortical expansion during folding of the preterm human brain
Authors: Garcia Kara E. , Robinson Emma C. , Alexopoulos Dimitrios , Dierker Donna L. , Glasser Matthew F. , Coalson Timothy S. , Ortinau Cynthia M. , Rueckert Daniel , Taber Larry A. , Van Essen David C. , Rogers Cynthia E. , Smyser Christopher D. , Bayly Philip V.
Published: September 2017

During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggests that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a new method to estimate local growth from sequential cortical reconstructions. Using anatomically-constrained Multimodal Surface Matching (aMSM), we obtain accurate, physically-guided point correspondence between younger and older cortical reconstructions of the same individual. From each pair of surfaces, we calculate continuous, smooth maps of cortical expansion with unprecedented precision. By considering 30 preterm infants scanned 2-4 times during the period of rapid cortical expansion (28 to 38 weeks postmenstrual age), we observe significant regional differences in growth across the cortical surface that are consistent with patterns of active folding. Furthermore, these growth patterns shift over the course of development, with non-injured subjects following a highly consistent trajectory. This information provides a detailed picture of dynamic changes in cortical growth, connecting what is known about patterns of development at the microscopic (cellular) and macroscopic (folding) scales. Since our method provides specific growth maps for individual brains, we are also able to detect alterations due to injury. This fully-automated surface analysis, based on tools freely available to the brain mapping community, may also serve as a useful approach for future studies of abnormal growth due to genetic disorders, injury, or other environmental variables.

Significance Statement

The human brain exhibits complex folding patterns that emerge during the third trimester of fetal development. Minor folds are quasi-randomly shaped and distributed. Major folds, in contrast, are more conserved and form important landmarks. Disruption of cortical folding is associated with devastating disorders of cognition and emotion. Despite decades of study, the processes that produce normal and abnormal folding remain unresolved, although the relatively rapid tangential expansion of the cortex has emerged as a driving factor. Accurate and precise measurement of cortical growth patterns during the period of folding has remained elusive. Here, we illuminate the spatiotemporal dynamics of cortical expansion by analyzing MRI-derived surfaces of preterm infant brains, using a novel strain energy minimization approach.
Vaccine waning and mumps re-emergence in the United States
Authors: Lewnard Joseph A. , Grad Yonatan H.
Published: September 2017

Following decades of declining mumps incidence amid widespread vaccination, the United States and other high-income countries have experienced a resurgence in mumps cases over the last decade. Outbreaks affecting vaccinated individuals—and communities with high vaccine coverage—have prompted concerns about the effectiveness of the live attenuated vaccine currently in use: it is unclear if immune protection wanes, or if the vaccine protects inadequately against mumps virus lineages currently circulating. Synthesizing data from epidemiological studies, we estimate that vaccine-derived protection wanes at a timescale of 27 (95%CI: 16 to 51) years. After accounting for this waning, we identify no evidence of changes in vaccine effectiveness over time associated with the emergence of heterologous virus genotypes. Moreover, a mathematical model of mumps transmission validates our findings about the central role of vaccine waning in the re-emergence of cases: outbreaks from 2006 to the present among young adults, and outbreaks occurring in the late 1980s and early 1990s among adolescents, align with peaks in the susceptibility of these age groups attributable to loss of vaccine-derived protection. In contrast, evolution of mumps virus strains escaping pressure would be expected to cause a higher proportion of cases among children. Routine use of a third dose at age 18y, or booster dosing throughout adulthood, may enable mumps elimination and should be assessed in clinical trials.

One Sentence Summary

The estimated waning rate of vaccine-conferred immunity against mumps predicts observed changes in the age distribution of mumps cases in the United States since 1967.
Administration of orexin A in the posterior paraventricular nucleus of the thalamus promotes cocaine-seeking behavior and is associated with hypothalamic activation
Authors: Matzeu Alessandra , Martin-Fardon Rémi
Published: September 2017

Hypothalamic orexin (Orx) neurons that project to the paraventricular nucleus of the thalamus (PVT) have received growing interest because of their role in drug-seeking behavior. When injected in the posterior PVT (pPVT), OrxA reinstated extinguished cocaine-seeking behavior in rats that had long access (LgA) to cocaine for 6 h/day after an intermediate period of abstinence (I-Abst, 2-3 weeks). Considering the long-lasting nature of drug-seeking behavior and that the PVT sends projections to the hypothalamus, the present study examined whether (i) OrxA’s priming effect is preserved after a period of protracted abstinence (P-Abst, 4-5 weeks) in LgA rats and (ii) the neural activation pattern (i.e., Fos+and Fos+/Orx+cells) in the lateral hypothalamus (LH), dorsomedial hypothalamus (DMH), and perifornical area (PFA) following intra-pPVT OrxA administration that may explain OrxA-induced reinstatement in LgA animals. As reported previously, OrxA administration in the pPVT triggered cocaine-seeking behavior after I-Abst. With P-Abst, the priming effect of OrxA was absent. An intra-pPVT injection of OrxA produced a strong increase in neuronal activation (i.e., Fos expression) in the LH/DMH/PFA at I-Abst but not at P-Abst. The analysis of the activation (Fos+) of Orx neurons (Orx+) revealed an increase in Fos+/Orx+expression in the LH/DMH/PFA at I-Abst only, thus paralleling the behavioral data. These data indicate that shortly after abstinence, PVT↔LH/DMH/PFA connections are strongly recruited in animals with a history of cocaine dependence. The lack of effect at P-Abst suggests that the function of Orx receptors and connectivity of the PVT↔LH/DMH/PFA circuit undergo significant neuroadaptations following P-Abst.

SIGNIFICANCE STATEMENT

A better understanding of the pathophysiological changes associated with cocaine addiction is needed to develop efficient pharmacotherapies. The paraventricular nucleus of the thalamus (PVT) and orexin (Orx) transmission within the PVT have been implicated in maladaptive (compulsive) behavior that is characteristic of drug addiction. The present study shows OrxA injections in the posterior PVT reinstates cocaine-seeking behavior in animals with a history of cocaine dependence, and this effect disappears after protracted abstinence, paralleled by the neuronal activation pattern in the hypothalamus. In subjects with a history of cocaine dependence, the function of Orx receptors and connectivity of the PVT↔ LH/DMH/PFA circuit undergo significant neuroadaptations.
Likelihood analysis of population genetic data under coalescent models: computational and inferential aspects
Authors: Rousset François , Beeravolu Champak Reddy , Leblois Raphaël
Published: September 2017

Likelihood methods are being developed for inference of migration rates and past demographic changes from population genetic data. We survey an approach for such inference using sequential importance sampling techniques derived from coalescent and diffusion theory. The consistent application and assessment of this approach has required the re-implementation of methods often considered in the context of computer experiments methods, in particular of Kriging which is used as a smoothing technique to infer a likelihood surface from likelihoods estimated in various parameter points, as well as reconsideration of methods for sampling the parameter space appropriately for such inference. We illustrate the performance and application of the whole tool chain on simulated and actual data, and highlight desirable developments in terms of data types and biological scenarios.

Diverses approches ont été développées pour l’inférence des taux de migration et des changements démo-graphiques passés à partir de la variation génétique des populations. Nous décrivons une de ces approches utilisant des techniques d’échantillonnage pondéré séquentiel, fondées sur la modélisation par approches de coalescence et de diffusion de l’évolution de ces polymorphismes. L’application et l’évaluation systématique de cette approche ont requis la ré-implémentation de méthodes souvent considérées pour l’analyse de fonctions simulées, en particulier le krigeage, ici utilisé pour inférer une surface de vraisemblance à partir de vraisemblances estimées en différents points de l’espace des paramètres, ainsi que des techniques d’échantillonage de ces points. Nous illustrons la performance et l’application de cette série de méthodes sur données simulées et réelles, et indiquons les améliorations souhaitables en termes de types de données et de scénarios biologiques.

Mots-clés

histoire démographique, processus de coalescence, importance sampling, genetic polymorphism

AMS 2000 subject classifications

92D10, 62M05, 65C05
Channel crosstalk correction in suspension and imaging mass cytometry
Authors: Chevrier Stéphane , Crowell Helena , Zanotelli Vito , Engler Stefanie , Robinson Mark D. , Bodenmiller Bernd
Published: September 2017

Mass cytometry enables simultaneous analysis of over 40 proteins and their modifications in single cells through use of metal-tagged antibodies. Compared to fluorescent dyes, the use of pure metal isotopes strongly reduces spectral overlap among measurement channels. Crosstalk still exists, however, caused by isotopic impurity, oxide formation, and mass cytometer properties. Spillover effects can be minimized, but not avoided, by following a set of constraining rules when designing an antibody panel. Generation of such low crosstalk panels requires considerable expert knowledge, knowledge of the abundance of each marker and substantial experimental effort. Here we describe a novel bead-based compensation workflow that includes R-based software and a web tool, which enables correction for interference between channels. We demonstrate utility in suspension mass cytometry and show how this approach can be applied to imaging mass cytometry. Our approach greatly simplifies the development of new antibody panels, increases flexibility for antibody-metal pairing, improves overall data quality, thereby reducing the risk of reporting cell phenotype and function artifacts, and greatly facilitates analysis of complex samples for which antigen abundances are unknown.
Modeling Marek’s disease virus transmission: a framework for evaluating the impact of farming practices and evolution on disease
Authors: Kennedy David A. , Dunn Patricia A. , Read Andrew F.
Published: September 2017

Marek’s disease virus (MDV) is a pathogen of chickens whose control has twice been un-dermined by pathogen evolution. Disease ecology is believed to be the main driver of this evolution, yet mathematical models of MDV disease ecology have never been confronted with data to test their reliability. Here, we develop a suite of MDV models that differ in the ecological mechanisms they include. We fit these models with maximum likelihood in ‘pomp’ to data on MDV concentration in dust collected from two commercial broiler farms. Using AIC to compare the models, we find that virus dynamics are influenced by between-flock variation in host susceptibility to virus, shedding rate from infected birds, and cleanout efficiency. We also find evidence that virus is reintroduced to farms approximately once per month, but we do not find evidence that virus sanitization rates vary between flocks. Of the models that survive model selection, we find agreement between parameter estimates and previous experimental data, as well as agreement between field data and the predictions of these models, suggesting robustness of model predictions. Using the set of surviving models, we explore how changes to farming practices are predicted to influence MDV costs, should pathogen evolution undermine existing control measures. By quantitatively capturing the mechanisms of disease ecology, we have laid the groundwork to explore the future trajectory of virus evolution.
mosdepth: quick coverage calculation for genomes and exomes
Authors: Pedersen Brent S. , Quinlan Aaron R.
Published: September 2017

Mosdepthis a new command-line tool for rapidly calculating genome-wide sequencing coverage. It measures depth from BAM (Li et al. 2009) or CRAM files at either each nucleotide position in a genome or for sets of genomic regions. Genomic regions may be specified as either a BED file to evaluate coverage across capture regions, or as a fixed-size window as required for copy-number calling. Mosdepth uses a simple algorithm that is computationally efficient and enables it to quickly produce optional coverage summaries. We demonstrate thatmosdepthis faster than existing tools and provides flexibility in the types of coverage profiles produced.

Availability

mosdepthis available fromhttps://github.com/brentp/mosdepthunder the MIT license‥

Contact

bpederse@gmail.com,aaronquinlan@gmail.com

Supplementary information

Detailed documentation is available athttps://github.com/brentp/mosdepth
Complemented palindrome small RNAs first discovered from SARS coronavirus
Authors: Liu Chang , Chen Ze , Shen Wenyuan , Yu Deshui , Li Siyu , Hu Yue , Ji Haishuo , Bu Wenjun , Wang Qingsong , Gao Shan
Published: September 2017

In this study, we reported for the first time the existence of complemented palindrome small RNAs (cpsRNAs) and proposed cpsRNAs and palindrome small RNAs (psRNAs) as a novel class of small RNAs. The first discovered cpsRNA UCUUUAACAAGCUUGUUAAAGAfrom SARS coronavirus named SARS-CoV-cpsR-22 contained 22 nucleotides perfectly matching its reverse complementary sequence. Further sequence analysis supported that SARS-CoV-cpsR-22 originated from bat betacoronavirus. The results of RNAi experiments showed that one 19-nt segment of SARS-CoV-cpsR-22 significantly induced cell apoptosis. These results suggested that SARS-CoV-cpsR-22 could play a role in SARS-CoV infection or pathogenicity. The discovery of psRNAs and cpsRNAs paved the way to find new markers for pathogen detection and reveal the mechanisms in the infection or pathogenicity from a different point of view. The discovery of psRNAs and cpsRNAs also broaden the understanding of palindrome motifs in animal of plant genomes.