bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Pancreaticogastrostomy Decrease the Occurrence of Delayed Gastric Emptying After Pancreatoduodenectomy?
Authors: Vandermeeren Chloé , Loi Patrizia , Closset Jean
Published: August 2017

Objectives

This study investigates the factors that could influence the development of delayed gastric emptying (DGE) after pancreatoduodenectomy (PD). Delayed gastric emptying is a common complication after PD. The postoperative course is affected by a lengthened hospital stay, a decrease of the patients' quality of life, and a delayed adjuvant treatment.

Methods

From January 2000 to December 2012, 257 patients underwent PD in the same center. Forty-six variables were retrospectively extracted from medical records. Delayed gastric emptying (grades A, B, and C) was defined by the International Study Group of Pancreatic Surgery classification. Univariate and multivariate analyses were performed to identify factors associated with DGE.

Results

Delayed gastric emptying occurred in 133 patients (51.8%), 89 grade A (66.9%), 27 grade B (20.3%), and 17 grade C (12.8%). Biliary fistula (odds ratio [OR], 8.87; 95% confidence interval [CI], 2.07–37.99, P = 0.003), sepsis (OR, 8.02; 95% CI, 3.22–19.99; P < 0.0001), and intra-abdominal collection (OR, 3.43; 95% CI, 1.06–11.06; P = 0.039) were identified as independent risk factors for DGE, whereas pancreaticogastrostomy (OR, 0.32; 95% CI, 0.16–0.64; P < 0.001) decreased the occurrence of DGE.

Conclusions

Delayed gastric emptying was linked to the occurrence of postoperative intra-abdominal complications, and reconstruction by pancreaticogastrostomy was beneficial by decreasing its incidence.
Primary Osteosarcoma of the Rib: A Case Report and Review of the Literature
Authors: Yaman Bajin İnci , Kurucu Nilgün , Oğuz Berna , Akçören Zuhal , Varan Ali , Şatirer Özlem , Akyüz Canan
Published: August 2017

Osteosarcoma is the most common primary malignant tumor of the bone. The most common sites of osteosarcoma in children are the metaphysis of long bones, especially the distal femur, proximal tibia, and proximal humerus. It occurs very rarely in flat bones. Here we report a 14-year-old adolescent boy with primary osteosarcoma of the fifth rib and a review of literature.
Immune Reconstitution Inflammatory Syndrome After DLI in a SCID Patient After Hematopoetic Stem Cell Transplantation
Authors: Kocacik Uygun Dilara F. , Uygun Vedat , Daloğlu Hayriye , Öztürkmen Seda I. , Karasu Gülsün T. , Hazar Volkan , Yeşilipek Akif
Published: August 2017

Immune reconstitution inflammatory syndrome (IRIS) is a clinical condition emerging after immune recovery of an immunocompromised status, mostly in human immunodeficiency virus infected patients but also in several other settings, such as the recovery from the severe combined immunodeficiency status after hematopoietic stem cell transplantation. Herein, we report a patient transplanted for severe combined immunodeficiency who developed IRIS for 2 times, namely shortly after transplantation and after donor lymphocyte infusion. Pediatric transplant teams need to be aware of the previous IRIS phenomenon of BCG-adenitis while making the decision of donor lymphocyte infusions.
Disease Distribution in Low-stage Tubo-ovarian High-grade Serous Carcinoma (HGSC): Implications for Assigning Primary Site and FIGO Stage
Authors: Singh Naveena , Benson Jack L. , Gan Carmen , Anglesio Michael , Arora Rupali , Faruqi Asma Z. , Hirschowitz Lynn , Kommoss Friedrich , Scott Kerry , Trevisan Giorgia , Leen Sarah Lam Shang , Wilkinson Nafisa , Gilks C. Blake , McCluggage W. Glenn
Published: August 2017

The latest FIGO and TNM (eighth edition) staging systems for ovarian, tubal, and peritoneal neoplasms require primary site assignment as tubal/ovarian/peritoneal, but provide no guidance or criteria. Fewer than 10% of extrauterine high-grade serous carcinoma (HGSC) cases present at low stage (stage I/II). Low-stage cases offer a unique opportunity to understand the pattern of disease early in its evolution prior to wide dissemination and provide valuable evidence for guiding specimen handling and tumor staging. This study aimed to examine disease distribution in low-stage tubo-ovarian HGSC. Anonymized pathology reports of 152 stage I/II extrauterine HGSCs from 6 teaching hospitals were analyzed: group 1 (n=67) comprised cases with complete tubal examination by Sectioning and Extensively Examining the FIMbriated end of the tube (SEE-FIM) and group 2 (n=85) consisted of cases without documentation of both tubes being fully examined by the SEE-FIM or a SEE-FIM-like protocol. The stage, site/pattern of involvement, site/size of largest tumor focus and laterality of tubal and ovarian involvement were recorded. Tubal mucosal involvement was present in 95% of optimally examined cases and many factors influenced detection of tubal disease. Bilateral involvement, suggestive of metastasis, was significantly more frequent in the ovaries (35%) than the tubes (9%) (P<0.0001, Fisher exact test). No case showed a complete absence of tubal/ovarian involvement, questioning the biological existence of primary peritoneal HGSC. Disease distribution in low-stage cases supports a tubal origin for most HGSCs. Detailed tubal sampling upstages some apparent stage I cases through detection of microscopic tubal involvement.
Epithelioid Inflammatory Myofibroblastic Sarcoma of the Ovary With RANB2-ALK Fusion: Report of a Case
Authors: Fang Hong , Langstraat Carrie L. , Visscher Daniel W. , Folpe Andrew L. , Schoolmeester J. Kenneth
Published: August 2017

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a recently described, clinically aggressive variant of inflammatory myofibroblastic tumor with a predilection for intraabdominal sites, tendency to arise in male patients and resistance to conventional chemotherapy and radiotherapy. We present a case of a 15-year-old girl with EIMS of the ovary with a RANBP2-ALK fusion. During 2 years of follow up, she experienced multiple recurrences. Following classification of the tumor as EIMS, the patient began treatment with an ALK inhibitor (crizotinib), which led to disease improvement within weeks of administration. To the best of our knowledge, this represents the first reported case of EIMS arising in the female genital tract.
A Rare Case of Primary Apocrine Adenocarcinoma Arising Within a Mature Cystic Teratoma of the Ovary, Metastatic to a Supraclavicular Lymph Node
Authors: Holmes Melissa , Robb Tanya
Published: August 2017

Mature cystic teratoma of the ovary is one of the most common benign tumours among reproductive aged women. Malignant transformation of a mature cystic teratoma is uncommon and metastatic malignancy is extremely rare. We report the first known case of an apocrine adenocarcinoma arising within an ovarian mature cystic teratoma which on follow-up six months later was found to be metastatic to the left supraclavicular lymph node. There are usually no pre-operative findings to raise the suspicion of malignancy in an ovarian teratoma, so awareness by the pathologist is therefore paramount.
Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study
Authors: Wu Shaowei , Gennings Chris , Wright Rosalind J. , Wilson Ander , Burris Heather H. , Just Allan C. , Braun Joseph M. , Svensson Katherine , Zhong Jia , Brennan Kasey J.M. , Dereix Alexandra , Cantoral Alejandra , Schnaas Lourdes , Téllez-Rojo Martha Maria , Wright Robert O. , Baccarelli Andrea A.
Published: August 2017

Objective

Maternal stress during pregnancy may influence childhood growth and adiposity, possibly through immune/inflammatory programming. We investigated whether exposure to prenatal stress and methylation in inflammation-related genes were associated with childhood adiposity in 424 mother-child pairs in Mexico City, Mexico.

Methods

A stress index was created based on four prenatally administered stress-related scales (Exposure to Violence, Crisis in Family Systems, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale). We measured weight, height, body fat mass (BFM), percentage body fat (PBF), and waist circumference in early childhood (age range, 4–6 years). Body mass index (BMI) z scores were calculated according to World Health Organization standards. DNA methylation in gene promoters of tumor necrosis factor α, interleukin 8, and interleukin 6 (IL6) in umbilical cord blood were determined by pyrosequencing.

Results

An interquartile range increase in stress index (27.3) was associated with decreases of 0.14 unit in BMI z score (95% confidence interval [CI] = −0.28 to −0.005), 5.6% in BFM (95% CI = −9.7 to −1.4), 3.5% in PBF (95% CI = −6.3 to −0.5), and 1.2% in waist circumference (95% CI = −2.4 to −0.04) in multivariable-adjusted models. An interquartile range increase in IL6 methylation (3.9%) was associated with increases of 0.23 unit in BMI z score (95% CI = 0.06–0.40), 8.1% (95% CI = 2.3–14.3) in BFM, 5.5% (95% CI = 1.7–9.5) in PBF, and 1.7% (95% CI = 0.2–3.3) in waist circumference.

Conclusions

Prenatal stress was associated with decreased childhood adiposity, whereas cord blood IL6 methylation was associated with increased childhood adiposity in Mexican children.
Time without clocks: Human time perception based on perceptual classification
Authors: Roseboom Warrick , Fountas Zafeirios , Nikiforou Kyriacos , Bhowmik David , Shanahan Murray , Seth Anil K.
Published: August 2017

Despite being a fundamental dimension of experience, how the human brain generates the perception of time remains unknown. Here, we provide a novel explanation for how human time perception might be accomplished, based on non-temporal perceptual clas-sification processes. To demonstrate this proposal, we built an artificial neural system centred on a feed-forward image classification network, functionally similar to human visual processing. In this system, input videos of natural scenes drive changes in network activation, and accumulation of salient changes in activation are used to estimate duration. Estimates produced by this system match human reports made about the same videos, replicating key qualitative biases, including differentiating between scenes of walking around a busy city or sitting in a cafe or office. Our approach provides a working model of duration perception from stimulus to estimation and presents a new direction for examining the foundations of this central aspect of human experience.
Gain-of-function Shh mutants activate Smoin cisindependent of Ptch1/2 function
Authors: Casillas Catalina , Roelink Henk
Published: August 2017

Sonic Hedgehog (Shh) signaling is characterized by strict non-cell autonomy; cells expressing Shh do not respond to their ligand. Here, we identify several Shh mutations that gain the ability to activate the Hedgehog (Hh) pathwayin cis. This activation requires the extracellular cysteine rich domain of Smoothened, but is otherwise independent of Ptch1/2. Many of the identified mutations disrupt either a highly conserved catalytic motif found in peptidases or an a-helix domain frequently mutated in holoprosencephaly-causingSHHalleles. The expression of gain-of-function mutants often results in the accumulation of unprocessed Shh pro-peptide, a form of Shh we demonstrate is sufficient to activate the Hh response cell-autonomously. Our results demonstrate that Shh is capable of activating the Hh pathway via Smo independently of Ptch1/2, and that it harbors an intrinsic mechanism that prevents cell-autonomous activation of the pathway to favor non-cell autonomous signaling.
Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producingEnterobacter hormaechei
Authors: Roberts Leah W. , Harris Patrick N. A. , Forde Brian M. , Ben Zakour Nouri L. , Stanton-Cook Mitchell , Catchpoole Elizabeth , Phan Minh-Duy , Sidjabat Hanna E. , Bergh Haakon , Heney Claire , Gawthorne Jayde A. , Lipman Jeffrey , Allworth Anthony , Chan Kok-Gan , Chong Teik Min , Yin Wai-Fong , Schembri Mark A. , Paterson David L. , Beatson Scott A.
Published: August 2017

Carbapenem-resistant Enterobacteriaceae (CRE) represent one of the most urgent threats to human health posed by antibiotic resistant bacteria.Enterobacter hormaecheiand other members of theEnterobacter cloacaecomplex are the most commonly encounteredEnterobacterspp. within clinical settings, responsible for numerous outbreaks and ultimately poorer patient outcomes. Here we applied three complementary whole genome sequencing (WGS) technologies to characterise a hospital cluster ofblaIMP-4carbapenemase-producingE. hormaechei.

In response to a suspected CRE outbreak in 2015 within an Intensive Care Unit (ICU)/Burns Unit in a Brisbane tertiary referral hospital we used Illumina sequencing to determine that all outbreak isolates were sequence type (ST)90 and near-identical at the core genome level. Comparison to publicly available data unequivocally linked all 10 isolates to a 2013 isolate from the same ward, confirming the hospital environment as the most likely original source of infection in the 2015 cases. No clonal relationship was found to IMP-4-producing isolates identified from other local hospitals. However, using Pacific Biosciences long-read sequencing we were able to resolve the complete context of theblaIMP-4gene, which was found to be on a large IncHI2 plasmid carried by all IMP-4-producing isolates. Continued surveillance of the hospital environment was carried out using Oxford Nanopore long-read sequencing, which was able to rapidly resolve the true relationship of subsequent isolates to the initial outbreak. Shotgun metagenomic sequencing of environmental samples also found evidence of ST90E. hormaecheiand the IncHI2 plasmid within the hospital plumbing.

Overall, our strategic application of three WGS technologies provided an in-depth analysis of the outbreak, including the transmission dynamics of a carbapenemase-producingE. hormaecheicluster, identification of possible hospital reservoirs and the full context ofblaIMP-4on a multidrug resistant IncHI2 plasmid that appears to be widely distributed in Australia.
Clearance of senescent decidual cells by uterine natural killer cells drives endometrial remodeling during the window of implantation
Authors: Brighton Paul J , Maruyama Yojiro , Fishwick Katherine , Vrljicak Pavle , Tewary Shreeya , Fujihara Risa , Muter Joanne , Lucas Emma S , Yamada Taihei , Woods Laura , Lucciola Raffaella , Lee Yie Hou , Takeda Satoru , Ott Sascha , Hemberger Myriam , Quenby Siobhan , Brosens Jan J
Published: August 2017

In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells that control embryo implantation. Here we show that FOXO1 also causes acute senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner. Selective depletion or enrichment of this subpopulation revealed that decidual senescence drives the transient inflammatory response associated with endometrial receptivity. Further, senescent cells prevent differentiation of endometrial mesenchymal stem cells in decidualizing cultures. As the cycle progresses, IL-15 activated uterine natural killer (uNK) cells selectively target and clear senescent decidual cells through granule exocytosis. Our findings reveal that acute decidual senescence governs endometrial rejuvenation and remodeling at embryo implantation, and suggest a critical role for uNK cells in maintaining homeostasis in cycling endometrium.
Multivariate pattern analysis for MEG: a comprehensive comparison of dissimilarity measures
Authors: Guggenmos Matthias , Sterzer Philipp , Cichy Radoslaw M.
Published: August 2017

Multivariate pattern analysis (MVPA) methods such as decoding and representational similarity analysis (RSA) are growing rapidly in popularity for the analysis of magnetoencephalography (MEG) data. However, little is known about the relative performance and characteristics of the specific dissimilarity measures used to describe differences between evoked activation patterns. Here we used a multisession MEG dataset to qualitatively characterize a range of dissimilarity measures and to quantitatively compare them with respect to classification accuracy (for decoding) and between-session reliability of representational dissimilarity matrices (for RSA). We tested dissimilarity measures from a range of classifiers (Linear Discriminant Analysis - LDA, Support Vector Machine - SVM, Weighted Robust Distance - WeiRD, Gaussian Naive Bayes - GNB) and distances (Euclidean distance, Pearson correlation). In addition, we evaluated three key processing choices: 1) preprocessing (noise normalisation, removal of the pattern mean), 2) weighting classification accuracies by decision values, and 3) computing distances in three different partitioning schemes (non-cross-validated, cross-validated, within-class-corrected). Four main conclusions emerged from our results. First, multivariate noise normalization dramatically improved classification accuracies and the reliability of dissimilarity measures. Second, LDA, SVM and WeiRD yielded high peak classification accuracies and nearly identical time courses. Third, while using classification accuracies for RSA was markedly less reliable than continuous distances, this disadvantage was ameliorated by decision-value-weighting of classification accuracies. Fourth, the cross-validated Euclidean distance provided unbiased distance estimates and highly replicable representational dissimilarity matrices. Overall, we strongly advice the use of multivariate noise normalisation as a general preprocessing step, recommend LDA, SVM and WeiRD as classifiers for decoding and highlight the cross-validated Euclidean distance as a reliable and unbiased default choice for RSA.
Structural Basis of Mitochondrial Receptor Binding and GTP-Driven Conformational Constriction by Dynamin-Related Protein 1
Authors: Kalia Raghav , Wang Ray Yu-Ruei , Yusuf Ali , Thomas Paul V. , Agard David A. , Shaw Janet M. , Frost Adam
Published: August 2017

Mitochondrial inheritance, genome maintenance, and metabolic adaptation all depend on organelle fission byDynamin-RelatedProtein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogsMitochondrialDynamics 49 and 51 (MID49/MID51) andMitochondrialFissionFactor (MFF), but the mechanisms by which these proteins recruit DRP1 and regulate its activities are unknown. Here we present a cryoEM structure of human, full-length DRP1 bound to MID49 and an analysis of structure- and disease-based mutations. We report that GTP binding allosterically induces a remarkable elongation and rotation of the G-domain, Bundle-Signaling Element (BSE) and connecting hinge loops of DRP1. In this nucleotide-bound conformation, a distributed network of multivalent interactions promotes DRP1 copolymerization into a linear filament with MID49, MID51 or both. Subsequent GTP hydrolysis and exchange within the filament leads to receptor dissociation, shortening through disassembly, and concomitant curling of DRP1 oligomers into closed rings. The dimensions of the closed DRP1 rings are consistent with DRP1-constricted mitochondrial tubules observed in human cells. These structures are the first views of full-length, receptor- and nucleotide-bound dynamin-family GTPases and—in comparison with nucleotide-free crystal structures—teach us how these molecular machines perform mechanical work through nucleotide-driven allostery.
Edge effects on components of diversity and above‐ground biomass in a tropical rainforest
Authors: Razafindratsima Onja H. , Brown Kerry A. , Carvalho Fabio , Johnson Steig E. , Wright Patricia C. , Dunham Amy E.
Published: August 2017

Edge effects are among the most significant consequences of forest fragmentation. Therefore, understanding the impacts of edge creation on biodiversity is crucial for forest management and biological conservation.

In this study, we used trait‐based and phylogenetic approaches to examine the effects of fragmentation on components of diversity and above‐ground biomass of rainforest tree communities in Madagascar in forest edge vs. interior habitats.

Tree communities in forest edges showed lower phylogenetic diversity relative to those in interior habitats, suggesting that some clades may be more vulnerable to environmental filtering than others. Functional diversity was also significantly lower on the edge for productivity traits, but not for dispersal traits. Tree communities in the forest edge showed higher divergence of dispersal traits and lower divergence in productivity traits than expected, while functional diversity in interior forest did not differ from random expectations. This suggests that separate mechanisms affect productivity traits vs. dispersal traits in edge habitats.

There was no significant difference in above‐ground biomass between edge and interior habitats, suggesting that edge effects have not yet negatively influenced the forest's potential for carbon storage. However, these changes may not have occurred yet, given the slow turnover of tree communities.

Synthesis and applications. Our results highlight the role of edge effects in the erosion of functional and phylogenetic diversity of highly diverse tree communities. While above‐ground biomass did not appear to be affected by forest edge in our study, we suggest long‐term monitoring of forests for potential changes in ecosystem functioning. These findings also indicate the need to reduce edge creation and buffer existing edges for holistic biodiversity conservation.
Current Status of Gender and Racial/Ethnic Disparities Among Academic Emergency Medicine Physicians
Authors: Madsen Tracy E. , Linden Judith A. , Rounds Kirsten , Hsieh Yu‐Hsiang , Lopez Bernard L. , Boatright Dowin , Garg Nidhi , Heron Sheryl L. , Jameson Amy , Kass Dara , Lall Michelle D. , Melendez Ashley M. , Scheulen James J. , Sethuraman Kinjal N. , Westafer Lauren M. , Safdar Basmah
Published: August 2017

Objective

A 2010 survey identified disparities in salaries by gender and underrepresented minorities (URM). With an increase in the emergency medicine (EM) workforce since, we aimed to 1) describe the current status of academic EM workforce by gender, race, and rank and 2) evaluate if disparities still exist in salary or rank by gender.

Methods

Information on demographics, rank, clinical commitment, and base and total annual salary for full‐time faculty members in U.S. academic emergency departments were collected in 2015 via the Academy of Administrators in Academic Emergency Medicine (AAAEM) Salary Survey. Multiple linear regression was used to compare salary by gender while controlling for confounders.

Results

Response rate was 47% (47/101), yielding data on 1,371 full‐time faculty: 33% women, 78% white, 4% black, 5% Asian, 3% Asian Indian, 4% other, and 7% unknown race. Comparing white race to nonwhite, 62% versus 69% were instructor/assistant, 23% versus 20% were associate, and 15% versus 10% were full professors. Comparing women to men, 74% versus 59% were instructor/assistant, 19% versus 24% were associate, and 7% versus 17% were full professors. Of 113 chair/vice‐chair positions, only 15% were women, and 18% were nonwhite. Women were more often fellowship trained (37% vs. 31%), less often core faculty (59% vs. 64%), with fewer administrative roles (47% vs. 57%; all p < 0.05) but worked similar clinical hours (mean ± SD = 1,069 ± 371 hours vs. 1,051 ± 393 hours). Mean overall salary was $278,631 (SD ± $68,003). The mean (±SD) salary of women was $19,418 (±$3,736) less than men (p < 0.001), even after adjusting for race, region, rank, years of experience, clinical hours, core faculty status, administrative roles, board certification, and fellowship training.

Conclusions

In 2015, disparities in salary and rank persist among full‐time U.S. academic EM faculty. There were gender and URM disparities in rank and leadership positions. Women earned less than men regardless of rank, clinical hours, or training. Future efforts should focus on evaluating salary data by race and developing systemwide practices to eliminate disparities.
Ecological momentary analysis of the relations among stressful events, affective reactivity, and smoking among smokers with high versus low depressive symptoms during a quit attempt
Authors: Minami Haruka , Frank Brandon E. , Bold Krysten W. , McCarthy Danielle E.
Published: August 2017

Aims

To assess whether individuals trying to quit smoking who have high depressive symptoms (HD), compared with low depressive symptoms (LD): (1) report more frequent stressful events (SEs), (2) are more likely to smoke after SEs, (3) experience greater acute or persistent changes in affect after an SE, and (4) are at greater risk of smoking following affective changes.

Design

Smoking cessation data were analyzed using multi‐level path modeling to examine the moderating effects of depressive symptoms on relations among SEs, subsequent affect, and smoking.

Setting

An academic research center in Central New Jersey, USA.

Participants

Seventy‐one adult treatment‐seeking daily smokers recruited from 2010 to 2012.

Measurements

Baseline depressive symptoms [HD: Center for Epidemiological Studies Depression Scale (CES‐D) ≥ 16 versus LD: CES‐D < 16]; and real‐time ecological momentary assessment (EMA) reports of SEs, affect, and smoking assessed during 21 days post‐quit.

Findings

Multi‐level models indicated that HD smokers were more likely than LD smokers to report stressful events [odds ratio (OR) = 2.323, P = 0.009], but had similar post‐stress acute affective changes (negative affect: b = −0.117, P = 0.137, positive affect: b = 0.020, P = 0.805). Only HD smokers reported increased negative affect (NA) (b = 0.199, P = 0.030) and decreased positive affect (PA) up to 12 hours later (b = −0.217, P = 0.021), and greater lapse risk up to 24 hours after an SE (OR = 3.213, P = 0.017). The persistence of elevated NA and suppressed PA was partially explained by increased odds of subsequent SEs among HD smokers. However, the heightened stress–lapse association over 24 hours found in HD smokers was not fully explained by sustained aversive affect or subsequent SEs.

Conclusions

Depressed and non‐depressed smokers trying to quit appear to experience similar acute affective changes following stress: however, depressed smokers experience higher rates of exposure to stress, longer‐lasting post‐stress affective disturbance and greater risk of smoking lapse 12–24 hours after a stressful event than non‐depressed smokers.
Prenatal early food and multiple micronutrient supplementation trial reduced infant mortality in Bangladesh, but did not influence morbidity
Authors: Kallioinen Maija , Ekström Eva‐Charlotte , Khan Ashraful Islam , Lindström Emma , Persson Lars Åke , Rahman Anisur , Selling Katarina Ekholm
Published: August 2017

Aim

A previous maternal and infant nutrition intervention in rural Matlab, Bangladesh, showed that prenatal nutrient supplements improved child survival, but had no effect on size at birth. This secondary analysis examined whether prenatal multiple micronutrient supplements (MMS), on their own or combined with an early invitation to receive prenatal food supplements, affected child morbidity.

Methods

This randomised trial enrolled 4436 pregnant women from November 2001 to October 2003 and allocated them to early or standard invitations to food supplements, in the ninth and 20th weeks of pregnancy, respectively, and supplements of either the standard 60 mg iron with 400 μg folic acid, 30 mg iron with 400 μg folic acid or MMS. Quasi‐Poisson regression was used to analyse morbidity.

Results

There were 3560 single live births and 3516 had morbidity data. The incidence rates of fever, diarrhoea and acute lower respiratory tract infection were 15.3, 3.6 and 2.3 episodes per person‐year, respectively. The separate or combined interventions had no effect on morbidity up to 24 months.

Conclusion

Early invitations to prenatal food supplements or prenatal MMS had no effect on common infections in rural Bangladesh, suggesting that earlier findings on improved child survival were not mediated by an effect on child morbidity.
Unlicensed and off‐label uses of medicines: definitions and clarification of terminology
Authors: Aronson Jeffrey K. , Ferner Robin E.
Published: August 2017

The terms ‘licensed’, ‘unlicensed’, and ‘off‐label’, often used in relation to marketing and prescribing medicinal products, may confuse UK prescribers. To market a medicinal product in the UK requires a Marketing Authorization (‘product licence’) for specified indications under specified conditions, regulated by the Medicines and Healthcare products Regulatory Agency (MHRA). The Marketing Authorization includes the product's agreed terms of use (the ‘label’), described in the Summary of Product Characteristics (SmPC). Prescribing a licensed product outside those terms is called ‘off‐label’ prescribing. Products for which no‐one holds a UK Marketing Authorization are unlicensed. Prescribers can prescribe authorized products according to the conditions described in the SmPC (‘on‐label’) or outside those conditions (‘off‐label’). They can also prescribe unauthorized products, even if they are unlicensed in the UK, if they are licensed elsewhere or if they have been manufactured in the UK by a licensed manufacturer as a ‘special’. The complexities of this system can be understood by considering the status of the manufacturer of the product, the company that markets it (which may or may not be the same), the product itself, and its modes of use, and by emphasizing the word ‘authorized’. If a Marketing Authorization is granted to the supplier of a product, it will specify the authorized modes of use; the product will be prescribable as authorized (i.e. ‘on‐label’) or in other modes of use, which will all be off‐label. Unlicensed products with no authorized modes of use can be regarded as ‘unauthorized products’. All ‘specials’ can be regarded as authorized products lacking authorized modes of use.
Longitudinal tracking of academic progress during teacher preparation
Authors: Corcoran Roisin P. , O'Flaherty Joanne
Published: August 2017

Background

Given that the ultimate academic goal of many education systems in the developed world is for students to graduate from college, grades have a considerable bearing on how effective colleges are in meeting their primary objective. Prior academic performance informs predominantly the selection and retention of teacher candidates. However, there remains a dearth of evidence linking academic performance with outcomes in teacher preparation or the workplace.

Aim

This study examined pre‐service teachers' trajectories of academic growth during teacher preparation.

Sample

The sample comprised 398 pre‐service teachers – 282 (70.8%) males and 116 (29.1%) females.

Method

Academic growth was measured across eight time points over the course of 4 years. Pre‐service teachers' academic growth was analysed using linear and nonlinear latent growth models.

Results

Results indicate that academic growth was quadratic and, over time, decelerated, with no evidence of the Matthew effect or the compensatory effect. There was evidence of a connection between prior academic attainment and current grades.

Conclusion

Greater attention to academic growth during the college years, and particularly among pre‐service teachers, may enable greater achievement support for students.
Tectono‐sedimentary evolution of the Plio‐Pleistocene Corinth rift, Greece
Authors: Gawthorpe Robert L. , Leeder Mike R. , Kranis Haralambos , Skourtsos Emmanuel , Andrews Julian E. , Henstra Gijs A. , Mack Greg H. , Muravchik Martin , Turner Jenni A. , Stamatakis Michael
Published: August 2017

The onshore central Corinth rift contains a syn‐rift succession >3 km thick deposited in 5–15 km‐wide tilt blocks, all now inactive, uplifted and deeply incised. This part of the rift records upward deepening from fluviatile to lake‐margin conditions and finally to sub‐lacustrine turbidite channel and lobe complexes, and deep‐water lacustrine conditions (Lake Corinth) were established over most of the rift by 3.6 Ma. This succession represents the first of two phases of rift development – Rift 1 from 5.0–3.6 to 2.2–1.8 Ma and Rift 2 from 2.2–1.8 Ma to present. Rift 1 developed as a 30 km‐wide zone of distributed normal faulting. The lake was fed by four major N‐ to NE‐flowing antecedent drainages along the southern rift flank. These sourced an axial fluvial system, Gilbert fan deltas and deep lacustrine turbidite channel and lobe complexes. The onset of Rift 2 and abandonment of Rift 1 involved a 30 km northward shift in the locus of rifting. In the west, giant Gilbert deltas built into a deepening lake depocentre in the hanging wall of the newly developing southern border fault system. Footwall and regional uplift progressively destroyed Lake Corinth in the central and eastern parts of the rift, producing a staircase of deltaic and, following drainage reversal, shallow marine terraces descending from >1000 m to present‐day sea level. The growth, linkage and death of normal faults during the two phases of rifting are interpreted to reflect self‐organization and strain localization along co‐linear border faults. In the west, interaction with the Patras rift occurred along the major Patras dextral strike‐slip fault. This led to enhanced migration of fault activity, uplift and incision of some early Rift 2 fan deltas, and opening of the Rion Straits at ca. 400–600 ka. The landscape and stratigraphic evolution of the rift was strongly influenced by regional palaeotopographic variations and local antecedent drainage, both inherited from the Hellenide fold and thrust belt.
Cytokine responses to exercise and activity in patients with chronic fatigue syndrome: case–control study
Authors: Clark L V , Buckland M , Murphy G , Taylor N , Vleck V , Mein C , Wozniak E , Smuk M , White P D
Published: August 2017

Chronic fatigue syndrome (CFS) is characterized by fatigue after exertion. A systematic review suggested that transforming growth factor (TGF)-β concentrations are often elevated in cases of CFS when compared to healthy controls. This study attempted to replicate this finding and investigate whether post-exertional symptoms were associated with altered cytokine protein concentrations and their RNA in CFS patients. Twenty-four patients fulfilling Centers for Disease Control criteria for CFS, but with no comorbid psychiatric disorders, were recruited from two CFS clinics in London, UK. Twenty-one healthy, sedentary controls were matched by gender, age and other variables. Circulating proteins and RNA were measured for TGF-β, tumour necrosis factor (TNF), interleukin (IL)-8, IL-6 and IL-1β. We measured six further cytokine protein concentrations (IL-2, IL-4, IL-5, IL-10, IL-12p70, and interferon (IFN)-γ). Measures were taken at rest, and before and after both commuting and aerobic exercise. CFS cases had higher TGF-β protein levels compared to controls at rest (median (quartiles) = 43·9 (19·2, 61·8) versus 18·9 (16·1, 30·0) ng/ml) (P = 0·003), and consistently so over a 9-day period. However, this was a spurious finding due to variation between different assay batches. There were no differences between groups in changes to TGF-β protein concentrations after either commuting or exercise. All other cytokine protein and RNA levels were similar between cases and controls. Post-exertional symptoms and perceived effort were not associated with any increased cytokines. We were unable to replicate previously found elevations in circulating cytokine concentrations, suggesting that elevated circulating cytokines are not important in the pathophysiology of CFS.
A randomized double‐blind controlled trial comparing three sedation regimens during flexible bronchoscopy: Dexmedetomidine, alfentanil and lidocaine
Authors: Riachy Moussa , Khayat Georges , Ibrahim Ihab , Aoun Zeina , Dabar Georges , Bazarbachi Taha , Khalil Nadine , Habr Bassem
Published: August 2017

Introduction

No standardized sedation protocol is available for flexible bronchoscopy (FB).

Objectives

The aim of this study was to evaluate the efficacy and safety of three regimens used for sedation during FB.

Methods

This randomized double‐blind controlled trial assessed patients undergoing bronchoscopy and receiving lidocaine alone (C) or combined with dexmedetomidine (D) or alfentanil (A). Tolerance was assessed using the bronchoscopy score, and level of sedation was assessed using the Nursing Instrument for the Communication of Sedation. Safety was evaluated in terms of pulmonary function and vital signs.

Results

A total of 162 patients were enrolled. The bronchoscopy score was identical in all groups. Group D subjects were the most sedated (P = .013), whereas group A subjects were the least agitated. Linear regression showed a negative association between bronchoscopy score and age in A (β = –0.06; P = .001). Positive predictors of bronchoscopy score were female gender (β = 1.96; P = .003) in D and obesity (β = 2.41; P = .012), longer procedures (β = 0.08; P = .009) and female gender (β = 1.15; P = .038) in C. Longer procedures (β = –0.12; P = .010) was a negative predictor of bronchoscopy score in D. Desaturation, hypoxia and heart rate changes were most prevalent in group A. Hypotension was mostly observed in D.

Conclusions

No consistent differences were present between the three regimens; however, each was more appropriate in certain patient profiles. We consequently proposed a protocol as a first step towards standardizing sedation practice in FB in a patient‐tailored manner. A more comprehensive and detailed protocol including other sedative agents with their corresponding doses should be developed.
How is chronic non‐communicable respiratory conditions research reported in European newspapers? An impact assessment for policy
Authors: Pallari Elena , Lewison Grant , Sullivan Richard
Published: August 2017

Background

Newspapers are an important means for the communication of medical research findings to policy‐makers and the public, but may distort their views on the relative importance of research into, and burden from, different respiratory diseases.

Methods

A systematic search strategy based on respiratory‐related keywords was developed and translated into 15 European languages to identify relevant stories in 26 newspapers from eight countries in 2002‐2013. Details of the stories were recorded on Excel and coded based on the reported respiratory conditions (asthma, chronic obstructive pulmonary disease (COPD) and other) and research types. Each cited research study was identified on the Web of Science and downloaded for analysis.

Findings

There were far more stories about asthma than on COPD, although the amount of research was only modestly greater, and the disease burden far less. Epidemiology, lifestyle and genetics research received the most media attention but not in all newspapers, while means of diagnosis and quality of life were under‐reported in all newspapers. Journalists tended to over‐cite research from their country by a factor averaging four times more than other researchers. About 10% of stories included a quote from a commentator, especially those in the two UK newspapers, with most of the quotes from UK charities.

Conclusions

The balance between disease areas reported in European newspaper stories is very misleading. European policy‐makers and public may perceive asthma as more burdensome than it is and COPD much less. The study also showed that UK charities, but not those in other European countries, gained significant publicity from their contributions to these stories.
Endothelial dysfunction assessment by noninvasive peripheral arterial tonometry in patients with chronic obstructive pulmonary disease compared with healthy subjects
Authors: Malerba Mario , Radaeli Alessandro , Nardin Matteo , Clini Enrico , Carpagnano Giovanna Elisiana , Sciatti Edoardo , Salghetti Francesca , Bonadei Ivano , Platto Fabio , Vizzardi Enrico
Published: August 2017

Introduction

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease. The endothelial dysfunction likely plays a central role in increasing cardiovascular risk.

Objectives

This cross‐sectional, study investigated the prevalence and extent of endothelial dysfunction in patients with stable COPD.

Methods

Peripheral arterial tonometry (PAT) was measured by post‐ischemic reactive hyperemia index (RHI) in 16 COPD patients, 16 healthy controls and 16 subjects with treated systemic arterial hypertension (AH) and analysed with covariates condition (dyslipidemia, and medications).

Results

The prevalence of endothelial dysfunction was significantly higher in COPD group than in the other groups. Mean RHI was significantly lower in COPD patients compared with the other groups. At linear regression FEV1 and RHI were directly correlated (Spearman index = 0.553; P = .026). COPD patients in groups C and D according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages showed lower RHI compared with patients classified as A and B (P < .01). At multiple regression analysis the presence of dyslipidemia, COPD and AH were associated with the presence of endothelial dysfunction.

Conclusions

Endothelial dysfunction in stable COPD patients is probably implicated in the high cardiovascular comorbidity. This study suggests the potential utility of endothelial dysfunction evaluation in patients with COPD to a timely assessment and treatment for cardiac complications.
Pharmacology and drug development in rare diseases: the attractiveness and expertise of the French medical pharmacology
Authors: Micallef Joëlle , Boutouyrie Pierre , Blin Olivier
Published: August 2017

Developing drugs for rare disease can be challenging due to specific rare disease characteristics. The French Medical Pharmacology is structured and positioned to play a major role in orphan drug research and development due to the required expertise concentrated into pharmacology departments, exclusively implemented within the French university hospitals, public hospitals that are linked to a medical school (and often a pharmacy school) with numerous INSERM or CNRS labelled research units.

In addition, these structures allow a close collaboration between researchers, academic institutions and biotech start‐up (most of them being spin‐off of the academic structures). Also, within university hospitals are located the clinical investigation centres, linking to the F‐CRIN network and also to Inserm and hospitals, that enable care staff and researchers to be associated and clinical research protocols to be carried out on site, in full respect with ethic and regulatory aspects.

As a consequence, this intra and multidisciplinary expertise offers all resource to elaborate a tailored approach for orphan drug development, in new entities as well as in repositioning. For preclinical development: drug screening, candidate selection (taking into account PK, metabolism, variability and potential toxicity) and preclinical models (iPS, animal models) that could allow a better translation to human research. For clinical development, we will mention here dose determination, safety evaluation and Orphan Drug Designation and Protocol Assistance preparation and submission. For post marketing evaluation and surveys, the pharmacovigilance, addictovigilance and pharmacoepidemiology expertise, combined with access to large databases allow a better approach to orphan drug use and safety.

As outlined through two success stories (Charcot Marie Tooth, vascular Ehlers‐Danlos syndrome), the added value of French Medical Pharmacology structures and expertise has been evidenced in the know‐how, multidimensional and multidisciplinary approaches, allowing the development of numerous drugs that have been granted with Orphan Drug Designation and later Market Approval. Even if specific and possibly even more, the field of orphan drugs requires the respect of highest standards of safety and quality. French Medical Pharmacology intends to continue on this way and constantly improve his involvement in this field, committed to a single objective: answer the unmet medical need of patients with rare diseases.
Involved, inputting or informing: “Shared” decision making in adult mental health care
Authors: Bradley Eleanor , Green Debra
Published: August 2017

Background

A diagnosis of serious mental illness can impact on the whole family. Families informally provide significant amounts of care but are disproportionately at risk of carer burden when compared to those supporting people with other long‐term conditions. Shared decision making (SDM) is an ethical model of health communication associated with positive health outcomes; however, there has been little research to evaluate how routinely family is invited to participate in SDM, or what this looks like in practice.

Objective

This UK study aimed to better understand how the family caregivers of those diagnosed with SMI are currently involved in decision making, particularly decisions about treatment options including prescribed medication. Objectives were to

Explore the extent to which family members wish to be involved in decisions about prescribed medication

Determine how and when professionals engage family in these decisions

Identify barriers and facilitators associated with the engagement of family in decisions about treatment.

Participants

Open‐ended questions were sent to professionals and family members to elicit written responses. Qualitative responses were analysed thematically.

Results

Themes included the definition of involvement and “rules of engagement.” Staff members are gatekeepers for family involvement, and the process is not democratic. Family and staff ascribe practical, rather than recovery‐oriented roles to family, with pre‐occupation around notions of adherence.

Conclusions

Staff members need support, training and education to apply SDM. Time to exchange information is vital but practically difficult. Negotiated teams, comprising of staff, service users, family, peers as applicable, with ascribed roles and responsibilities could support SDM.
Fall migratory departure decisions and routes of blackpoll warblers Setophaga striata and red‐eyed vireos Vireo olivaceus at a coastal barrier in the Gulf of Maine
Authors: Smetzer Jennifer R. , King David I. , Taylor Philip D.
Published: August 2017

Each year, millions of songbirds concentrate in coastal areas during fall migration. The choices birds make at the coast about stopover habitat use and migratory route can influence both the success of their migratory journey and fitness in subsequent life stages. We made use of a regional‐scale automated radio telemetry array to study stopover and migratory flights and migratory routes of blackpoll warblers Setophaga striata and red‐eyed vireos Vireo olivaceus during fall migration in the Gulf of Maine, USA. We focused on differences between species, sexes, age groups, breeding origins, and time of year. Both species made within‐stopover relocations (i.e. ‘stopover flights’) from the coastal capture site. Stopover flights were primarily oriented inland, and were more frequent for blackpolls (87%) than vireos (44%). By studying migratory behavior at a broad spatial scale, we demonstrated that most blackpolls and vireos took coastal and offshore routes through the Gulf of Maine, despite initially relocating inland from the capture site. Though we captured blackpolls and vireos from a broad breeding range, more than 70% of migratory flights from the capture site were oriented for coastal or offshore travel for both species, suggesting that birds actively chose coastal and offshore routes, and were not simply displaced by wind drift. Later vireos oriented offshore more frequently during migratory flights from the coast, indicating that they may be more inclined towards time‐minimizing overwater flight routes and thus more exposed to coastal and offshore collision hazards than earlier conspecifics.