bluuebunny/crossref_metadata_2025 huggingface dataset:
A validated natural language processing algorithm for brain imaging phenotypes from radiology reports in UK electronic health records
Authors: Wheater Emily , Mair Grant , Sudlow Cathie , Alex Beatrice , Grover Claire , Whiteley William
Published: September 2019

Background

Manual coding of phenotypes in brain radiology reports is time consuming. We developed a natural language processing (NLP) algorithm to enable automatic identification of brain imaging in radiology reports performed in routine clinical practice in the UK National Health Service (NHS).

Methods

We used anonymized text brain imaging reports from a cohort study of stroke/TIA patients and from a regional hospital to develop and test an NLP algorithm. Two experts marked up text in 1692 reports for 24 cerebrovascular and other neurological phenotypes. We developed and tested a rule-based NLP algorithm first within the cohort study, and further evaluated it in the reports from the regional hospital.

Results

The agreement between expert readers was excellent (Cohen’s κ =0.93) in both datasets. In the final test dataset (n = 700) in unseen regional hospital reports, the algorithm had very good performance for a report of any ischaemic stroke [sensitivity 89% (95% CI:81–94); positive predictive value (PPV) 85% (76–90); specificity 100% (95% CI:0.99–1.00)]; any haemorrhagic stroke [sensitivity 96% (95% CI: 80–99), PPV 72% (95% CI:55–84); specificity 100% (95% CI:0.99–1.00)]; brain tumours [sensitivity 96% (CI:87–99); PPV 84% (73–91); specificity: 100% (95% CI:0.99–1.00)] and cerebral small vessel disease and cerebral atrophy (sensitivity, PPV and specificity all > 97%). We obtained few reports of subarachnoid haemorrhage, microbleeds or subdural haematomas. In 110,695 reports from NHS Tayside, atrophy (n = 28,757, 26%), small vessel disease (15,015, 14%) and old, deep ischaemic strokes (10,636, 10%) were the commonest findings.

Conclusions

An NLP algorithm can be developed in UK NHS radiology records to allow identification of cohorts of patients with important brain imaging phenotypes at a scale that would otherwise not be possible.
The effectiveness of military hospital-based drug treatment program (PMK) when compared with the traditional community-based drug treatment program (FAST)
Authors: Kaewkham Niramon , Leelahanaj Thawatchai , Yingwiwattanapong Jatsada , Rattanasumawong Wanida
Published: September 2019

Background

In Thailand, two community-based drug treatment approaches are common. The first one is the traditional community-based treatment program (FAST) which brings the principles of community therapy as a guideline for treatment. The second one is the military hospital-based drug treatment program (PMK), derived from the basic military training, the Buddhist Twelve Steps, CBT and the Minnesota Rehabilitation Model. This study aimed to investigate and compare the efficacy of PMK vs. FAST.

Method

The experiment was conducted from January–March 2016 at the rehabilitation center for patients with drug addiction in Thailand. Quasi-experimental methods were introduced, and ASSIST, WHOQOL-BRIEF-THAI and self-efficacy interview form were applied. After completing the drug rehabilitation program at a total duration of 120 days, the researcher continued at follow up times at 3 and 6 months.

Results

Compared with baseline scores, both programs significantly reduced the severity of drugs and increased self-efficacy at 6-month follow-up. PMK had better improved scores in the relationship and environment dimensions of quality of life at 3-month follow-up (P = 0.026, 0.006). The mean quality of life scores in PMK at 3 and 6 months showed better results than mean scores at baseline (P = < 0.001).

Conclusion

Both community-based programs in Thailand significantly reduced the severity of drugs and increased self-efficacy scores at 6-month follow-up. PMK and FAST has not shown any significant difference in treatment outcome results in the aspects of self-efficacy and reduced severity of drugs used. However, PMK had significant positive effects on the quality of life.
Enhancer variants associated with Alzheimer’s disease affect gene expression via chromatin looping
Authors: Kikuchi Masataka , Hara Norikazu , Hasegawa Mai , Miyashita Akinori , Kuwano Ryozo , Ikeuchi Takeshi , Nakaya Akihiro
Published: September 2019

Background

Genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that may be genetic factors underlying Alzheimer’s disease (AD). However, how these AD-associated SNPs (AD SNPs) contribute to the pathogenesis of this disease is poorly understood because most of them are located in non-coding regions, such as introns and intergenic regions. Previous studies reported that some disease-associated SNPs affect regulatory elements including enhancers. We hypothesized that non-coding AD SNPs are located in enhancers and affect gene expression levels via chromatin loops.

Methods

To characterize AD SNPs within non-coding regions, we extracted 406 AD SNPs with GWAS p-values of less than 1.00 × 10− 6 from the GWAS catalog database. Of these, we selected 392 SNPs within non-coding regions. Next, we checked whether those non-coding AD SNPs were located in enhancers that typically regulate gene expression levels using publicly available data for enhancers that were predicted in 127 human tissues or cell types. We sought expression quantitative trait locus (eQTL) genes affected by non-coding AD SNPs within enhancers because enhancers are regulatory elements that influence the gene expression levels. To elucidate how the non-coding AD SNPs within enhancers affect the gene expression levels, we identified chromatin-chromatin interactions by Hi-C experiments.

Results

We report the following findings: (1) nearly 30% of non-coding AD SNPs are located in enhancers; (2) eQTL genes affected by non-coding AD SNPs within enhancers are associated with amyloid beta clearance, synaptic transmission, and immune responses; (3) 95% of the AD SNPs located in enhancers co-localize with their eQTL genes in topologically associating domains suggesting that regulation may occur through chromatin higher-order structures; (4) rs1476679 spatially contacts the promoters of eQTL genes via CTCF-CTCF interactions; (5) the effect of other AD SNPs such as rs7364180 is likely to be, at least in part, indirect through regulation of transcription factors that in turn regulate AD associated genes.

Conclusion

Our results suggest that non-coding AD SNPs may affect the function of enhancers thereby influencing the expression levels of surrounding or distant genes via chromatin loops. This result may explain how some non-coding AD SNPs contribute to AD pathogenesis.
LncRNA SNHG6 promotes chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in colorectal cancer cells
Authors: Wang Xinke , Lan Zhixian , He Juan , Lai Qiuhua , Yao Xiang , Li Qingyuan , Liu Yongfeng , Lai Huasheng , Gu Chuncai , Yan Qun , Fang Yuxin , Zhang Yue , Li Aimin , Liu Side
Published: September 2019

Background

Chemotherapy resistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to poor prognosis. Long noncoding RNAs (lncRNAs) have been reported to regulate chemoresistance. We aimed to determine the role of the lncRNA small nucleolar RNA host gene 6 (SNHG6) in CRC cell chemoresistance.

Methods

Cell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. Animal models were used to determine chemoresistance in vivo, and micro RNA (miRNA) binding sites were detected by dual-luciferase reporter assays. Bioinformatics analysis was performed to predict miRNAs binding to SNHG6 and target genes of miR-26a-5p. SNHG6/miR-26a-5p/ULK1 axis and autophagy-related proteins were detected by qRT-PCR and western blotting. Furthermore, immunofluorescence was employed to confirm the presence of autophagosomes.

Results

SNHG6 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted autophagy, inhibited 5-FU-induced apoptosis, and increased 5-FU resistance in vivo. Bioinformatics analysis showed that miR-26a-5p might bind to SNHG6 and target ULK1, and dual-luciferase reporter assays confirmed this activity. qRT-PCR and western blotting showed that SNHG6 was able to negatively regulate miR-26a-5p but correlated positively with ULK1.

Conclusion

SNHG6 may promote chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in CRC cells.
Correction to: A repeated cross-sectional study of clinicians’ use of psychotherapy techniques during 5 years of a system-wide effort to implement evidence-based practices in Philadelphia
Authors: Beidas Rinad S. , Williams Nathaniel J. , Becker-Haimes Emily M. , Aarons Gregory A. , Barg Frances K. , Evans Arthur C. , Jackson Kamilah , Jones David , Hadley Trevor , Hoagwood Kimberly , Marcus Steven C. , Neimark Geoffrey , Rubin Ronnie M. , Schoenwald Sonja K. , Adams Danielle R. , Walsh Lucia M. , Zentgraf Kelly , Mandell David S.
Published: September 2019

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Adaptive step size algorithm to increase efficiency of proton macro Monte Carlo dose calculation
Authors: Kueng Reto , Frei Daniel , Volken Werner , Stuermlin Fabian , M. Stampanoni Marco F. , Aebersold Daniel M. , Manser Peter , Fix Michael K.
Published: September 2019

Purpose

To provide fast and accurate dose calculation in voxelized geometries for proton radiation therapy by implementing an adaptive step size algorithm in the proton macro Monte Carlo (pMMC) method.

Methods

The in-house developed local-to-global MMC method for proton dose calculation is extended with an adaptive step size algorithm for efficient proton transport through a voxelized geometry by sampling transport parameters from a pre-simulated database. Adaptive choice of an adequate slab size in dependence of material interfaces in the proton’s longitudinal and lateral vicinity is investigated. The dose calculation algorithm is validated against the non-adaptive pMMC and full MC simulation for pencil and broad beams with various energies impinging on academic phantoms as well as a head and neck patient CT.

Results

For material interfaces perpendicular to a proton’s direction, choice of nearest neighbor slab thickness shows best trade-off between dosimetric accuracy and calculation efficiency. Adaptive reduction of chosen slab size is shown to be required for material interfaces closer than 0.5 mm in lateral direction. For the academic phantoms, dose differences of within 1% or 1 mm compared to full Geant4 MC simulation are found, while achieving an efficiency gain of up to a factor of 5.6 compared to the non-adaptive algorithm and 284 compared to Geant4. For the head and neck patient CT, dose differences are within 1% or 1 mm with an efficiency gain factor of up to 3.4 compared to the non-adaptive algorithm and 145 compared to Geant4.

Conclusion

An adaptive step size algorithm for proton macro Monte Carlo was implemented and evaluated. The dose calculation provides the accuracy of full MC simulations, while achieving an efficiency gain factor of three compared to the non-adaptive algorithm and two orders of magnitude compared to full MC for a complex patient CT.
Human papilloma virus (HPV) genotypes concordance between Iranian couples referrals
Authors: Davarmanesh Mehrdad , Dezfulian Mehrouz , Gharavi Mohammad Javad , Younesi Sarang , Saadati Pourandokht , Amin Mohammad Mehdi Taheri , Jazayeri Seyed Mohammad
Published: September 2019

Background

Human Papilloma Virus (HPV) genotypes concordance among sexual couples has been evaluated in many investigations with considerable variations in the concordance. However, no such study has carried out between Iranian couples yet.

Methods

Urogenital specimen from both males and females of couples were taken and transferred to Nilou laboratory for molecular analysis. HPV DNA extraction and typing were carried out using cobas 4800 platform. Demographic and virological data were analyzed afterwards.

Results

One hundred fourteen couples were enrolled in the study. The mean age of participants were 36 ± 8 and 32 ± 7 for males and females, respectively. 64 (28%) of specimens were positive for at least one HPV genotype. The positive rates within genders were 30.7 and 25.4% for females and males, respectively with a considerable association (P value 0.021). Within the positive samples, 13(5.7%), 8 (7%) and 31(13.5%) were belonged to 16, 18 and other HR genotypes. 59 (51.8%) couples who were negative for HPV showed negative concordance. Of the total positive HPV patients (55 couples, 48.2%), 9 (16.3%) couples had positive concordance and the rest of 46 (83.7%) couples (either of spouse being negative and the other being positive for HPV) showed neither kinds of concordance.

Conclusion

Recognition of the dynamics of HPV infection not only in women, but in their sexual partners could impact the implementation of preventive measures like HPV vaccination for cervical cancer and other HPV-related diseases for both sexual partners.
Body weight at 10 years of age and change in body composition between 8 and 10 years of age were related to survival in a longitudinal study of 39 Labrador retriever dogs
Authors: Penell Johanna Christina , Morgan David Mark , Watson Penny , Carmichael Stuart , Adams Vicki Jean
Published: September 2019

Background

Overweight and obesity have been adversely associated with longevity in dogs but there is scarce knowledge on the relation between body composition and lifespan. We aimed to investigate the effects of body composition, and within-dog changes over time, on survival in adult Labradors using a prospective cohort study design. The dogs had a median age of 6.5 years at study start and were kept in similar housing and management conditions throughout. The effects of the various predictors, including the effect of individual monthly-recorded change in body weight as a time varying covariate, were evaluated using survival analysis.

Results

All dogs were followed to end-of-life; median age at end-of-life was 14.0 years. Body composition was measured annually with dual-energy x-ray absorptiometer (DEXA) scans between 6.2 and 17.0  years. All 39 dogs had DEXA recorded at 8, 9 and 10 years of age. During the study the mean (± SD) percent of fat (PF) and lean mass (PL) was 32.8 (± 5.6) and 64.2 (± 5.5) %, respectively, with a mean lean:fat ratio (LFR) of 2.1 (± 0.6); body weight (BW) varied from 17.5 to 44.0 kg with a mean BW change of 9.9 kg (± 3.0). There was increased hazard of dying for every kg increase in BW at 10 years of age; for each additional kg of BW at 10 years, dogs had a 19% higher hazard (HR = 1.19, P = 0.004). For the change in both lean mass (LM) and LFR variables, it was protective to have a higher lean and/or lower fat mass (FM) at 10 years of age compared to 8 years of age, although the HR for change in LM was very close to 1.0. For age at study start, older dogs had an increased hazard. There was no observed effect for the potential confounders sex, coat colour and height at shoulders, or of the time-varying covariate.

Conclusions

These results suggest that even rather late-life control efforts on body weight and the relationship between lean and fat mass may influence survival in dogs. Such “windows of opportunity” can be used to develop healthcare strategies that would help promote an increased healthspan in dogs.
CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis
Authors: Zhu Qian , Liu Nan , Orkin Stuart H. , Yuan Guo-Cheng
Published: September 2019

We introduce CUT&RUNTools as a flexible, general pipeline for facilitating the identification of chromatin-associated protein binding and genomic footprinting analysis from antibody-targeted CUT&RUN primary cleavage data. CUT&RUNTools extracts endonuclease cut site information from sequences of short-read fragments and produces single-locus binding estimates, aggregate motif footprints, and informative visualizations to support the high-resolution mapping capability of CUT&RUN. CUT&RUNTools is available at https://bitbucket.org/qzhudfci/cutruntools/.
N-acetylcysteine for cessation of tobacco smoking: rationale and study protocol for a randomised controlled trial
Authors: Arancini Lauren , Bortolasci Chiara C. , Dodd Seetal , Dean Olivia M. , Berk Michael
Published: September 2019

Background

Tobacco smoking is a highly prevalent, addictive behaviour and a key public health priority. However available cessation therapies have low quit and high relapse rates, indicating an urgent need for more effective treatments. Predicated on promising preclinical and pilot clinical data, this paper presents a rationale and protocol for the trial of N-acetylcysteine (NAC) as a novel anti-craving smoking cessation aid.

Methods

Current smokers (n = 120) of at least 10 cigarettes a day are recruited through online advertisements, print publications and dissemination of flyers. Participants are randomised on a 1:1 ratio to receive either 16-week treatment of 1.8 g/day of NAC or placebo with all participants receiving quit support from the online QuitCoach tool. Participants are attending visits at baseline, 8 and 16 weeks with a 42-week post-discontinuation follow-up. The primary outcome measure is sustained abstinence at six months after treatment based on self-reported rating scales and confirmed by exhaled carbon monoxide and salivary cotinine levels. Secondary outcomes are timing of the first lapse and relapse, between-group cigarette consumption, withdrawal symptoms, general wellbeing and mood/anxiety symptoms. Between-group differences in adverse events and subgroup analyses for variables including gender and Diagnostic Statistics Manual 5 diagnostics will also be investigated.

Discussion

The planned trial addresses an issue of major importance to human health and, if an effect is shown, may result in substantial changes to the management of smoking and nicotine addiction with overt public health implications.

Trial registration

Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12617001478303. Registered on 19 October 2017.
Performance of three delignifying pretreatments on hardwoods: hydrolysis yields, comprehensive mass balances, and lignin properties
Authors: Bhalla Aditya , Cai Charles M. , Xu Feng , Singh Sandip K. , Bansal Namita , Phongpreecha Thanaphong , Dutta Tanmoy , Foster Cliff E. , Kumar Rajeev , Simmons Blake A. , Singh Seema , Wyman Charles E. , Hegg Eric L. , Hodge David B.
Published: September 2019

Background

In this work, three pretreatments under investigation at the DOE Bioenergy Research Centers (BRCs) were subjected to a side-by-side comparison to assess their performance on model bioenergy hardwoods (a eucalyptus and a hybrid poplar). These include co-solvent-enhanced lignocellulosic fractionation (CELF), pretreatment with an ionic liquid using potentially biomass-derived components (cholinium lysinate or [Ch][Lys]), and two-stage Cu-catalyzed alkaline hydrogen peroxide pretreatment (Cu-AHP). For each of the feedstocks, the pretreatments were assessed for their impact on lignin and xylan solubilization and enzymatic hydrolysis yields as a function of enzyme loading. Lignins recovered from the pretreatments were characterized for polysaccharide content, molar mass distributions, β-aryl ether content, and response to depolymerization by thioacidolysis.

Results

All three pretreatments resulted in significant solubilization of lignin and xylan, with the CELF pretreatment solubilizing the majority of both biopolymer categories. Enzymatic hydrolysis yields were shown to exhibit a strong, positive correlation with the lignin solubilized for the low enzyme loadings. The pretreatment-derived solubles in the [Ch][Lys]-pretreated biomass were presumed to contribute to inhibition of enzymatic hydrolysis in the eucalyptus as a substantial fraction of the pretreatment liquor was carried forward into hydrolysis for this pretreatment. The pretreatment-solubilized lignins exhibited significant differences in polysaccharide content, molar mass distributions, aromatic monomer yield by thioacidolysis, and β-aryl ether content. Key trends include a substantially higher polysaccharide content in the lignins recovered from the [Ch][Lys] pretreatment and high β-aryl ether contents and aromatic monomer yields from the Cu-AHP pretreatment. For all lignins, the13C NMR-determined β-aryl ether content was shown to be correlated with the monomer yield with a second-order functionality.

Conclusions

Overall, it was demonstrated that the three pretreatments highlighted in this study demonstrated uniquely different functionalities in reducing biomass recalcitrance and achieving higher enzymatic hydrolysis yields for the hybrid poplar while yielding a lignin-rich stream that may be suitable for valorization. Furthermore, modification of lignin during pretreatment, particularly cleavage of β-aryl ether bonds, is shown to be detrimental to subsequent depolymerization.
Metabolic engineering of Bacillus amyloliquefaciens for enhanced production of S-adenosylmethionine by coupling of an engineered S-adenosylmethionine pathway and the tricarboxylic acid cycle
Authors: Ruan Liying , Li Lu , Zou Dian , Jiang Cong , Wen Zhiyou , Chen Shouwen , Deng Yu , Wei Xuetuan
Published: September 2019

Background

S-Adenosylmethionine (SAM) is a critical cofactor involved in many biochemical reactions. However, the low fermentation titer of SAM in methionine-free medium hampers commercial-scale production. The SAM synthesis pathway is specially related to the tricarboxylic acid (TCA) cycle in Bacillus amyloliquefaciens. Therefore, the SAM synthesis pathway was engineered and coupled with the TCA cycle in B. amyloliquefaciens to improve SAM production in methionine-free medium.

Results

Four genes were found to significantly affect SAM production, including SAM2 from Saccharomyces cerevisiae, metA and metB from Escherichia coli, and native mccA. These four genes were combined to engineer the SAM pathway, resulting in a 1.42-fold increase in SAM titer using recombinant strain HSAM1. The engineered SAM pathway was subsequently coupled with the TCA cycle through deletion of succinyl-CoA synthetase gene sucC, and the resulted HSAM2 mutant produced a maximum SAM titer of 107.47 mg/L, representing a 0.59-fold increase over HSAM1. Expression of SAM2 in this strain via a recombinant plasmid resulted in strain HSAM3 that produced 648.99 mg/L SAM following semi-continuous flask batch fermentation, a much higher yield than previously reported for methionine-free medium.

Conclusions

This study reports an efficient strategy for improving SAM production that can also be applied for generation of SAM cofactors supporting group transfer reactions, which could benefit metabolic engineering, chemical biology and synthetic biology.
Identification of critical factors that significantly affect the dose-response in mosquitoes irradiated as pupae
Authors: Yamada Hanano , Maiga Hamidou , Juarez Jose , De Oliveira Carvalho Danilo , Mamai Wadaka , Ali Adel , Bimbile-Somda Nanwintoum Severin , Parker Andrew Gordon , Zhang Dongjing , Bouyer Jeremy
Published: September 2019

Background

The sterile insect technique (SIT) for use against mosquitoes consists of several steps including the production of the target species in large numbers, the separation of males and females, the sterilization of the males, and the packing, transport and release of the sterile males at the target site. The sterility of the males is the basis of the technique; for this, efficient and standardized irradiation methods are needed to ensure that the required level of sterility is reliably and reproducibly achieved. While several reports have found that certain biological factors, handling methods and varying irradiation procedures can alter the level of induced sterility in insects, few studies exist in which the methodologies are adequately described and discussed for the reproductive sterilization of mosquitoes. Numerous irradiation studies on mosquito pupae have resulted in varying levels of sterility. Therefore, we initiated a series of small-scale experiments to first investigate variable parameters that may influence dose-response in mosquito pupae, and secondly, identify those factors that potentially have a significantly large effect and need further attention.

Methods

In this study, we compiled the results of a series of experiments investigating variable parameters such as pupal age (Aedes aegypti), pupal size (Ae. aegypti), geographical origin of mosquito strains (Ae. aegyptiandAe. albopictus), exposure methods (in wetversusdry conditions,Ae. albopictus) and subsequently in lowversushigh oxygen environments [submerged in water (low O2(< 5 %)] and in air [high O2(~ 21 %)] on the radiosensitivity of male pupae (Ae. aegypti,Ae. albopictusandAnopheles arabiensis).

Results

Results indicate that radiosensitvity ofAe. aegyptidecreases with increasing pupal age (99% induced sterility in youngest pupae, compared to 93% in oldest pupae), but does not change with differences in pupal size (P = 0.94). Differing geographical origin of the same mosquito species did not result in variations in radiosensitivity inAe. aegyptipupae [Brazil, Indonesia, France (La Reunion), Thailand] orAe. albopictus[Italy, France (La Reunion)]. Differences in induced sterility were seen following irradiation of pupae that were in wetversusdry conditions, which led to further tests showing significant radioprotective effects of oxygen depletion during irradiation procedures in three tested mosquito species, as seen in other insects.

Conclusions

These findings infer the necessity to further evaluate significant factors and reassess dose-response for mosquitoes with controlled variables to be able to formulate protocols to achieve reliable and reproducible levels of sterility for application in the frame of the SIT.
Sex differences in fetal growth and immediate birth outcomes in a low-risk Caucasian population
Authors: Galjaard Sander , Ameye Lieveke , Lees Christoph C. , Pexsters Anne , Bourne Tom , Timmerman Dirk , Devlieger Roland
Published: September 2019

Background

According to the WHO Multicentre Growth Reference Study Group recommendations, boys and girls have different growth trajectories after birth. Our aim was to develop gender-specific fetal growth curves in a low-risk population and to compare immediate birth outcomes.

Methods

First, second, and third trimester fetal ultrasound examinations were conducted between 2002 and 2012. The data was selected using the following criteria: routine examinations in uncomplicated singleton pregnancies, Caucasian ethnicity, and confirmation of gestational age by a crown-rump length (CRL) measurement in the first trimester. Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used to align the time frames of the longitudinal fetal measurements, corresponding with the methods of the postnatal growth curves of the WHO MGRS Group.

Results

A total of 27,680 complete scans were selected from the astraia© ultrasound database representing 12,368 pregnancies. Gender-specific fetal growth curves for biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were derived. The HC and BPD were significantly larger in boys compared to girls from 20 weeks of gestation onwards (p < 0.001) equating to a 3-day difference at 20–24 weeks. Boys were significantly heavier, longer, and had greater head circumference than girls (p < 0.001) at birth. The Apgar score at 1 min (p = 0.01) and arterial cord pH (p < 0.001) were lower in boys.

Conclusions

These longitudinal fetal growth curves for the first time allow integration with neonatal and pediatric WHO gender-specific growth curves. Boys exceed head growth halfway of the pregnancy, and immediate birth outcomes are worse in boys than girls. Gender difference in intrauterine growth is sufficiently distinct to have a clinically important effect on fetal weight estimation but also on the second trimester dating. Therefore, these differences might already play a role in early fetal or immediate neonatal management.
Stability-preserving model order reduction for linear stochastic Galerkin systems
Authors: Pulch Roland
Published: September 2019

Mathematical modeling often yields linear dynamical systems in science and engineering. We change physical parameters of the system into random variables to perform an uncertainty quantification. The stochastic Galerkin method yields a larger linear dynamical system, whose solution represents an approximation of random processes. A model order reduction (MOR) of the Galerkin system is advantageous due to the high dimensionality. However, asymptotic stability may be lost in some MOR techniques. In Galerkin-type MOR methods, the stability can be guaranteed by a transformation to a dissipative form. Either the original dynamical system or the stochastic Galerkin system can be transformed. We investigate the two variants of this stability-preserving approach. Both techniques are feasible, while featuring different properties in numerical methods. Results of numerical computations are demonstrated for two test examples modeling a mechanical application and an electric circuit, respectively.
A convenient and efficient total solid-phase synthesis of DOTA-functionalized tumor-targeting peptides for PET imaging of cancer
Authors: Okarvi Subhani M. , AlJammaz Ibrahim
Published: September 2019

Introduction

An efficient and cost-effective synthesis of the metal chelating agents that couple to tumor-targeting peptides is required to enhance the process of preclinical research toward the clinical translation of molecular imaging agents. DOTA is one of the most widely used macrocyclic ligands for the development of new metal-based imaging and therapeutic agents owing to its ability to form stable and inert complexes under physiological conditions. Although solid-phase synthesis compatible DOTA-tris-(t-Bu ester) is a commercial product, it is expensive and contain chemical impurities. There is a need to explore new and cost-effective methods for the preparation of metal chelating agents, i.e., DOTA, directly on solid support to facilitate rapid, cost-effective, and high purity preparation of DOTA-linked peptides for imaging and therapy. In the present study, we describe a facile synthetic strategy of DOTA preparation and its linkage to peptides directly on solid-phase support.

Methods

Bombesin (BN) peptides were functionalized with DOTA chelator prepared from cyclen precursor on solid-phase and from commercial DOTA-tris and radiolabeled with 68Ga. In vitro BN/GRP receptor binding affinities of the corresponding radiolabeled peptides were determined by saturation binding assays on human breast MDA-MB-231, MCF7, T47D, and PC3 prostate cancer cells. Pharmacokinetics were studied in Balb/c mice and in vivo tumor targeting in MDA-MB-231 tumor-bearing nude mice.

Results

DOTA was prepared successfully from cyclen on solid-phase support, linked specifically to BN peptides and resultant DOTA-coupled peptides were radiolabeled efficiently with 68Ga. The binding affinities of all the six BN peptides were comparable and in the low nanomolar range. All 68Ga-labeled peptides showed high metabolic stability in plasma. These radiopeptides exhibited rapid pharmacokinetics in Balb/c mice with excretion mainly through the urinary system. In nude mice, MDA-MB-231 tumor uptake profiles were slightly different; the BN peptide with Ahx spacer and linked to DOTA through cyclen exhibited higher tumor uptake (2.32% ID/g at 1 h post-injection) than other radiolabeled BN peptides investigated in this study. The same leading BN peptide also displayed favorable pharmacokinetic profile in Balb/c mice. The PET images clearly visualized the MDA-MB-231 tumor.

Conclusions

DOTA prepared from cyclen on solid-phase support showed comparable potency and efficiency to DOTA-tris in both in vitro and in vivo evaluation. The synthetic methodology described here allows versatile, site-specific introduction of DOTA into peptides to facilitate the development of DOTA-linked molecular imaging and therapy agents for clinical translation.
End-user experiences with two incident and injury reporting systems designed for led outdoor activities - challenges for implementation of future data systems
Authors: Finch Caroline F. , Goode Natassia , Shaw Louise , Salmon Paul M.
Published: September 2019

Background

Injury and incident (near miss) prevention is heavily dependent upon robust and high-quality data systems. Evaluations of surveillance systems designed to report factors associated with incidents and injuries are essential to understand their value, as well as to improve their performance and efficiency. Despite, this there have been few such evaluations published in the peer-review literature.

Methods

The attitudes and experiences of industry representatives who used one of two variants of an incident and injury surveillance system to collect injury and incident data for the led outdoor activity setting were obtained through an online self-report survey following a 12-month trial. Survey respondents were 18 representatives of 33 organisations who were users of a comprehensive incident reporting and surveillance system – the Understanding and Preventing Led Outdoor Accidents Data System Software Tool (UPLOADS-ST) - and six out of 11 users of a modified system (UPLOADS-Lite). The survey collected information on user experiences in relation to system training, accessibility, ease of use, security, feedback and perceived value to the sector of collating and reporting data across organisations.

Findings

Only four UPLOADS-ST responding users found the system easy to use and just three considered entering incident reports to be easy. However, many considered the training on reporting incidents to be sufficient and that the incident reports contained relevant details. Fewer than half of respondents (seven for UPLOADS-ST, three for UPLOADS-Lite) believed entering data was a good use of staff time and resources. Nonetheless, a majority of respondents (seven for UPLOADS-ST, five for UPLOADS-Lite) found the reporting format easy to read and felt the information provided was useful for their organisation.

Conclusions

Usability barriers to incident reporting were identified, particularly for UPLOADS-ST, including time constraints and user friendliness. The majority of users believed aggregating and reporting incident and injury data across organisations would be of value in making the led outdoor activity sector safer. Improving the utility of the surveillance systems will assist in ensuring their sustainability in the led outdoor activity sector.
Comparison of video demonstrations and bedside tutorials for teaching paediatric clinical skills to large groups of medical students in resource-constrained settings
Authors: George Ann , Blaauw Duane , Green-Thompson Lionel , Hajinicolaou Christina , Lala Nilesh , Parbhoo Kiran , Rodda John , Velaphi Sithembiso , Kala Udai , Vallabh Preeteeben , Dangor Ziyaad , Lala Sanjay G.
Published: September 2019

Videos are increasingly being used for teaching clinical skills in medical education. However, most reports on the effectiveness and benefits of videos in medical teaching have come from developed countries. Resource constraints in South African academic hospitals, together with increasing numbers, may apply pressure on the standard of clinical teaching. This study investigated the potential for using video demonstrations to replace the bedside teaching of introductory paediatric clinical examination skills to large groups of medical students. Sixty medical students were randomised to an experimental group that watched a video of a paediatric abdominal examination or to a control group that received a bedside tutorial on the same topic. Immediately afterwards, experienced assessors observed and scored the students in a clinical examination. Data were analysed for the non-inferiority of the video group scores within a 10% margin of the bedside group. Students’ and clinician educators’ perceptions of the two teaching methods and their views on how video instruction could be integrated into the clinical teaching programme were explored. Qualitative data were analysed thematically. The video teaching was non-inferior to the bedside teaching within the 10% margin and did not significantly affect the pass/fail or distinction rates. Students and clinician educators suggested that the videos be used for teaching basic concepts, allowing bedside tutorials to focus on applied learning. The findings have important implications for using video demonstrations to supplement the teaching of clinical skills to large groups of medical students across multiple variably-resourced settings.
Suicide and the psychiatrist
Authors: House Allan
Published: September 2019

Research into patient suicide indicates that it has an impact on the psychiatrists involved, but leaves a number of unanswered questions about which elements of the experience are most likely to cause problems, who is most at risk, what is the clinical or professional significance of any effect on the psychiatrist and how other professionals are affected. Despite these uncertainties, it is clear that a response is needed, with three bodies responsible in different ways for coordinating one: the relevant mental health trust, as employer; the Royal College of Psychiatrists, as the professional representative body; and the National Confidential Inquiry into Suicide and Safety in Mental Health, as mediator of social and professional impact.
Baseline Functional Connectivity Predicts Connectivity Changes Due to a Small Dose of Midazolam in Older Adults
Authors: Frölich Michael A. , White David M. , Kraguljac Nina V. , Lahti Adrienne C.
Published: September 2019

BACKGROUND:

In the perioperative context, benzodiazepines are widely used as anxiolytics. They affect cognition in general, but it is unclear whether the effects of a small dose of the short-acting benzodiazepine midazolam can be assessed objectively. To address this scientific question, we conducted a prospective observational study in adults 55–73 years of age. Using both validated psychometric and functional imaging techniques, we determined whether a 2-mg intravenous (IV) dose of midazolam affects cognitive function.

METHODS:

We measured the effect of 2 mg IV of midazolam with both the well-established Repeatable Battery for the Assessment of Neuropsychological Status test and resting-state functional magnetic imaging (rs-fMRI) in older adults.

RESULTS:

Midazolam reduces immediate and delayed memory and has a profound and robust effect on rs-fMRI. Baseline resting-state connectivity predicts memory decline after midazolam administration.

CONCLUSIONS:

Observed effects of midazolam on brain networks were statistically significant even in a small group of volunteers. If validated by other investigators, resting-state brain connectivity may have utility as a measure to predict sensitivity to midazolam in older adults.
IL VIAGGIO: METODO D’INDAGINE ORIGINALE
Authors: Perra Livio
Published: September 2019

In questo articolo l’autore analizza i viaggi di Montesquieu, dove si manifesta il trionfo del piacere della scoperta. Il viaggio è indagine della realtà sociale, politica e istituzionale. Le certezze e le nozioni iniziali sono riconsiderate o temprate dalle conferme dell’osservata realtà. Il viaggio con una vena di disincanto porta con sé il fascino di nuove idee e diventa strumento originale di analisi comparativa della realtà europea dell’epoca. L’autore vuole sottolineare l’imprescindibilità del viaggio nella formazione delle rifl essioni di Montesquieu. La teoria da sola non è suffi ciente, il barone de La Brède trova nel suo cammino per l’Europa l’ispirazione che solo l’osservazione empirica può dare. Scrutare la realtà da vicino diviene fondamentale, fa comprendere a Montesquieu come siano numerose le variabili che infl uenzano gli eventi e la politica di uno Stato. L’autore, dopo l’attenta analisi effettuata, giunge alla conclusione che alcune delle riflessioni contenute nel De l’Esprit des Lois, oltre che di derivazione libresca, sono figlie dell’originale metodo d’indagine costituito dai viaggi di Montesquieu.
Η εισαγωγή του e-mentoring ως θεσμού υποδοχής-υποστήριξης των νεοεισερχόμενων εκπαιδευτικών στην πρωτοβάθμια εκπαίδευση: Μια μελέτη περίπτωσης
Authors: Γιάνναρου Γεωργία , Αλεξανδρόπουλος Γεώργιος
Published: September 2019

Η παρούσα έρευνα μελετά τις δυνατότητες και τα εμπόδια της αξιοποίησης του e-mentoring στην υποδοχή-υποστήριξη των νεοεισερχόμενων εκπαιδευτικών. Το δείγμα αποτέλεσαν 155 άτομα, με δειγματοληψία μη πιθανότητας, από τους περίπου 350 νεοεισερχόμενους στην πρωτοβάθμια εκπαίδευση της περιφερειακής ενότητας Ηλείας τα έτη 2014-2017. Για τη συλλογή των δεδομένων χρησιμοποιήθηκε πρωτότυπο ερωτηματολόγιο, ενώ τα ερευνητικά ερωτήματα αφορούσαν τη γνώση της νομοθεσίας, τη λειτουργική διεισδυτικότητα του e-mentoring, την αντίσταση / την προτίμηση σε αυτό σε σχέση με κάποιο άλλο τρόπο υποδοχής-υποστήριξης των εκπαιδευτικών και την ομοιογένεια των απόψεων. Πραγματοποιήθηκαν στατιστικοί έλεγχοι με τα κριτήρια Pearson's chi-squared (χ²) και Spearman's rho σε επίπεδο στατιστικής σημαντικότητας α = 0,05.Από τα ευρήματά μας φαίνεται ότι οι περισσότεροι νεοεισερχόμενοι έχουν συγκεχυμένη εικόνα για την υποστήριξη-αξιολόγησή τους και διαφωνούν με τον νέο θεσμό, τον οποίο δεν θεωρούν αποτελεσματικότερο σε σχέση με το πρόσωπο με πρόσωπο mentoring και το δείγμα είναι εξαιρετικά ομοιογενές. Επίσης, στην εκπαιδευτική κοινότητα υπάρχουν σε μεγαλύτερο βαθμό οι τεχνικές δυνατότητες για την εισαγωγή του e-mentoring παρά οι διοικητικές.Προτείνεται η πιλοτική εφαρμογή του, καθώς και η διεύρυνση του σχετικού προβληματισμού αναφορικά με τη σχέση της ανοικτότητας του e-mentoring με την αξιολόγηση στο δημόσιο και το εργασιακό άγχος.
Υλοποίηση ενός MOOC με Drupal για την Εφαρμογή της Μικρομάθησης και της Αυτοκατευθυνόμενης Μάθησης
Authors: Καμήλαλη Δέσποινα Σπύρος , Σοφιανοπούλου Χρύσα
Published: September 2019

Τα Massive Open Online Courses (MOOCs) είναι ανοιχτά διαδικτυακά μαθήματα που ξεκίνησαν το 2012 από κορυφαία Πανεπιστήμια της Αμερικής και προσέλκυσαν χιλιάδες εκπαιδευόμενους από όλο τον κόσμο. Ο παιδαγωγικός τους σχεδιασμός αρχικά διακρινόταν στα κονεκτιβιστικά cMOOCs και στα Γνωστικά – Συμπεριφοριστικά xMOOCs, με την πάροδο όμως του χρόνου εξελίχθηκαν και εμφανίστηκαν και άλλες προτάσεις διδακτικού σχεδιασμού στις διάφορες πλατφόρμες (Conole, 2013).Αντικείμενο κριτικής για την επιτυχία των MOOCs αποτελούν τα ποσοστά εγκατάλειψής τους από τους εκπαιδευόμενους. Αν και τα μεγάλα ποσοστά αποτυχίας των MOOCs μπορούν να εξηγηθούν από το ότι πολλοί εγγράφονται μόνο από περιέργεια ή για να εξερευνήσουν το υλικό, χωρίς να έχουν σκοπό να αποκτήσουν την πιστοποίηση, ωστόσο, είναι ανάγκη να εξερευνηθούν νέες παιδαγωγικές πρακτικές για τη βελτίωσή τους, ώστε να ολοκληρώνουν με επιτυχία όσοι θα το ήθελαν.Προκειμένου να μελετηθεί η συνδυασμένη εφαρμογή του Microlearning και του Self-Directed Learning σαν νέα παιδαγωγική πρακτική, υλοποιήθηκε σε ένα website Drupal, ένα MOOC με αντικείμενο εκπαίδευσης το Drupal. Οι εκπαιδευόμενοι, μελετούσαν το εκπαιδευτικό υλικό και δημιουργούσαν το δικό τους website Drupal.Στόχος της παρούσας εργασίας είναι:Να περιγράψει τη μεθοδολογία σχεδίασης και υλοποίησης του MOOC, για την εφαρμογή των θεωριών της Μικρομάθησης – Microlearning και της Αυτοκατευθυνόμενης Μάθησης – Self-Directed Learning (SDL) με τη χρήση του CMS Drupal.
Teaching mathematical concepts using web-based collaborative enviroments. An eTwinning case study
Authors: Αλεξίου (Alexiou) Λαμπρινή (Labrini) Νικόλαος
Published: September 2019

eTwinning is an innovative European program that strengthens lifelong learning and the main purpose of which is the networking of schools with the help of new technologies. It is an initiative of the European Commission to strengthen the collaborative distance learning and the implementation of new innovative instructional methods. Through literature review, this article explores the contribution of the eTwinning project to the cultivation of basic skills, which the European Parliament identifies as keys to an individual's lifelong learning. Mathematics are included in these skills. It is an attempt to show the schools' potential to cultivate the students' European identity and European skills, such as cooperation and respect for the perceptions and culture of other people. It is also a case study aimed at exploring the cognitive, creative, cooperative and technological dimensions of an eTwinning action, as well as the attitude of 18 students towards the distance learning action, which they participated in. Τhe subject of the eTwinning practice combines mathematical concepts applied in real context.
Management of nocturia: overcoming the challenges of nocturnal polyuria
Authors: Suman Sanjay , Robinson Dudley , Bhal Nadia , Fraser Susannah , MacCormick Angus , Williams Ann , Tadtayev Sergey
Published: September 2019

Nocturia may be a multifactorial condition and should be regarded as a syndrome rather than a diagnosis, with many factors contributing to the clinical presentation. The effects of sleep deprivation can have a severely detrimental impact on the quality of life and productivity of the working age population, with considerable economic implications. Patients are unlikely to seek an appointment with their GP complaining of nocturia – they are more likely to complain of the effects of the condition, such as chronic tiredness, or injuries resulting from falls. The main criterion in deciding whether a patient should undergo further investigations into suspected nocturia is the degree to which the patient finds the condition bothersome. In some patients, lifestyle modifications may be an effective way to manage nocturia before medication is considered. As the only licensed product for all adults including those over 65 years of age, low dose desmopressin (Noqdirna® (as lyophilisate) Ferring Pharmaceuticals Ltd) is highly effective in the management of idiopathic nocturnal polyuria, producing improvements in clinical symptoms, sleep parameters and quality of life. Care should be administered as a joint enterprise between the patient's GP and colleagues in secondary care. This article outlines the findings of a roundtable discussion into the optimal management of patients with nocturnal polyuria.
Systemic sclerosis
Authors: Hughes Michael , Herrick Ariane L
Published: September 2019

Systemic sclerosis is a complex autoimmune connective tissue disease which carries a significant burden of disease-related morbidity including potentially life-threatening complications. Systemic sclerosis can affect all the major organs and therefore, although the disease is uncommon, many hospital-based specialists are involved in patient care. Vascular disease (e.g. Raynaud's phenomenon) is an almost universal symptom in patients with systemic sclerosis and is often the earliest manifestation of the disease. Systemic sclerosis not uncommonly can overlap with other rheumatological conditions (e.g. rheumatoid arthritis and myositis). During the past few decades there have been major advances in understanding the pathogenesis of systemic sclerosis and these are driving advances in treatment. There are now a number of effective treatments to manage many of the different organ-based complications. Autologous haemopoietic stem cell transplantation is a potential treatment option in highly selected patients. This review updates the clinician about epidemiology, pathogenesis, differential diagnosis, the wide clinical spectrum of disease, and current and emerging treatments for systemic sclerosis.
Urinary catheterization 1: indications
Authors: Tan Elizabeth , Ahluwalia Aashish , Kankam Hadyn , Menezes Pravin
Published: September 2019

Urinary catheterization is an important procedure that is regularly performed in hospital. All clinicians should have a good working knowledge of urinary catheters and the competence to manage them effectively. This topic will be discussed over two articles: this first article will focus on indications, and the second on techniques and managing failure. There are multiple indications for urethral catheter insertion and a range of catheter types and sizes. The choice of catheter is dependent on the patient and indication. This article discusses this in more detail to help guide clinicians involved in urethral catheterization.