bluuebunny/crossref_metadata_2025 huggingface dataset:
Teaching the German Superlative
Authors: Fagan Sarah M. B.
Published: May 2019

The basic form of the superlative suffix in German is ‐st (kleinst‐), with some adjectives requiring a longer form, ‐est (lautest‐). While the superlative has long been a topic in teaching materials, the accuracy of textbook treatments continues to be less than satisfactory. The difficulty arises in characterizing the adjectives that require the longer form of the suffix. Grammars provide no standard treatment of the superlative and fail to present concise generalizations, crucial to the language learner. This paper provides a new analysis of the superlative that incorporates the insights revealed in an evaluation of accounts of the superlative in three grammars of German. Stress, secondary as well as primary, the feature [coronal], and the recognition of complex segments are argued to be crucial for describing the environments in which ‐e‐ must be inserted before the ‐st suffix. The rule describing these environments is stated both in formal terms and in terms that are accessible to the language learner, and suggestions are provided for teaching.
RHD genotyping of serologic RhD‐negative blood donors in a hospital‐based blood donor center
Authors: Perez‐Alvarez Ingrid , Hayes Chelsea , Hailemariam Tiruneh , Shin Edward , Hutchinson Tyler , Klapper Ellen
Published: May 2019

BACKGROUND

Serologic RhD‐negative blood donors are tested by a method known to detect weak D antigen expression. Serology does not detect all red blood cells with RhD expression and RHD genotyping has been used to identify variant RHD alleles, which may lead to some RhD expression. The aim of this study was to determine the frequency of RHD variant alleles in serologic RhD‐negative blood donors at a hospital‐based donor center in Los Angeles.

STUDY DESIGN AND METHODS

RHD genotyping of serologic RhD‐negative blood donors over a 20‐month period was performed using the Immucor RHD BeadChip assay. DNA sequencing was performed when the RHD BeadChip assay failed to assign a genotype. For RHD variants known or suspected to result in RhD expression, recipients of previous blood donations were investigated for alloimmunization.

RESULTS

RHD genotyping was performed in 1174 RhD‐negative blood donors, and 1122 were genotyped for RHCE variants. Eleven donors (0.94%) harbored mutations predicted to yield RhD expression. The predicted phenotypes were, in decreasing frequency, DEL, partial, and weak D phenotypes. Anti‐D was not detected in 16 patients who had received blood from these donors after an average follow up of 182 days.

CONCLUSION

Genotyping can be used to identify donors with the potential to sensitize RhD‐negative recipients. In this limited study, 0.94% of serologic RhD‐negative blood donors were found to have variant RHD alleles that might cause alloimmunization in RhD‐negative recipients. To our knowledge, a study of this nature has not been reported in the United States.
Utility of temperature‐sensitive indicators for temperature monitoring of red‐blood‐cell units
Authors: Park Mikyoung , Hur Mina , Yi Ahram , Kim Hanah , Lee Hyun Kyung , Jeon Eun Young , Oh Kyung‐Mi , Lee Mark Hong
Published: May 2019

Background and Objectives

The 30‐min rule has been used to maintain a core temperature (CT) of red‐blood‐cell (RBC) units below 10°C during transportation. We evaluated the utility of temperature‐sensitive indicators (TIs) to monitor the surface temperature (ST) of RBC units and to explore whether TIs can help with compliance with the 30‐min rule by extrapolating or correlating temperature change with time.

Materials and Methods

Two US FDA‐approved TIs, Safe‐T‐Vue 10 (STV10; Temptime Corporation, Morris Plains, NJ, USA) and Timestrip Blood Temp 10 (BT10; Timestrip UK Ltd, Cambridge, UK), were attached to 50 RBC units. After issue, their colour change indicating 10°C was monitored, and temperature excursions were measured by standard reading. In additional 18 RBC units, both ST and CT were monitored simultaneously.

Results

In 50 RBC units, 94% of STV10 and 100% of BT10 showed colour change indicating 10°C within 30 min; 4% of STV10 and 18% of BT10 showed it during transportation. The time for colour change indicating 10°C differed significantly between STV10 and BT10 (19·0 vs. 5·6 min, P < 0·001). In additional 18 RBC units, 83·3% of STV10, 100% of BT10 and 88·9% of CT reached 10°C within 30 min, and the time for colour change indicating 10°C was 24·4 min in STV10, 14·6 min in BT 10 and 24·2 min in CT (P < 0·001).

Conclusion

In two TIs, the time for colour change indicating 10°C varied considerably. To enhance the utility of TIs, further improvement and standardization would be needed.
Neurological signs and MRI findings in 12 dogs with multiple myeloma
Authors: Wyatt Sophie , De Risio Luisa , Driver Colin , José‐López Roberto , Pivetta Mauro , Beltran Elsa
Published: May 2019

Vertebral lesions and associated neurological signs occur in dogs with multiple myeloma, however, veterinary literature describing MRI findings is currently lacking. The objective of this multicenter, retrospective, case series study was to describe neurological signs and MRI findings in a group of dogs that presented for spinal pain or other neurological deficits and had multiple myeloma. Electronic records of four veterinary referral hospitals were reviewed. Dogs were included if they had a pathologically confirmed diagnosis of multiple myeloma, had presented for spinal pain or other neurological signs, and had undergone MRI of the vertebral column. The MRI studies were evaluated and the anatomical location of lesion(s), signal intensity, presence of extra‐dural material, degree of spinal cord compression, extent of vertebral lesions, and contrast enhancement were recorded. Twelve dogs met inclusion criteria. Most dogs (n = 8) had a chronic progressive history, with varying degrees of proprioceptive ataxia and paresis (n = 11), and spinal pain was a feature in all dogs. The MRI findings were variable but more consistent features included the presence of multiple expansile vertebral lesions without extension beyond the outer cortical limits of affected vertebrae, and associated extradural material causing spinal cord compression. The majority of lesions were hyper‐ to isointense on T2 (n = 12) and T1‐weighted (n = 8) sequences, with variable but homogeneous contrast‐enhancement (n = 12). These described MRI characteristics of multiple myeloma may be used to aid early identification and guide subsequent confirmatory diagnostic steps, to ultimately improve therapeutic approach and long‐term outcome.
Frailty phenotype and frailty index are associated with distinct neuromuscular electrophysiological characteristics in men
Authors: Swiecicka Agnieszka , Piasecki Mathew , Stashuk Daniel W. , Ireland Alex , Jones David A. , Rutter Martin K. , McPhee Jamie S.
Published: May 2019

New Findings

What is the central question of this study?

Human frailty is characterized by accumulated health complaints, including medical conditions, low physical and psychological function and social components. It is currently unknown whether the condition is associated with neuromuscular changes detectable by electrophysiology obtained from voluntary and involuntary muscle contractions.

What is the main finding and its importance?

A higher likelihood of frailty was significantly associated with a smaller size of vastus lateralis motor unit potentials during voluntary contractions and smaller compound muscle action potentials generated by electrical stimulation. Importantly, these associations were independent of age and body mass index.

The purpose of this study was to determine whether neuromuscular electrophysiological characteristics that are known to underlie sarcopenia are also associated with the more complex frailty syndrome. Eighty‐six men [mean (SD) age, 74 (8) years] were classed as non‐frail (robust), prefrail or frail using criteria from the frailty phenotype (FP) and the frailty index (FI). The femoral nerve was stimulated maximally and the resulting compound muscle action potential amplitude (CMAP) measured over the vastus lateralis. Motor unit potential (MUP) size was assessed during voluntary contractions using intramuscular electromyography (iEMG). Logistic and negative binomial regression models determined relationships between FP and FI with CMAP and MUP sizes before and after adjustments for age and body mass index. Larger CMAP size was associated with a lower likelihood of frailty in fully adjusted models: a 1SD higher level in vastus lateralis CMAP size was associated with a 0.4 (95% confidence interval: 0.2, 0.6; P < 0.01) unit lower FI (40% of the FI range) and more than halving of the odds [odds ratio: 0.43 (95% confidence interval: 0.21, 0.90)] of having a frail/prefrail phenotype. Greater MUP size was also related to lower FI values using unadjusted and fully adjusted models. However, MUP size was not significantly related to FP in any model. Smaller MUPs and a smaller CMAP were significantly associated with a higher likelihood of frailty, independent of age and body mass index. These results relate neuromuscular electrophysiological characteristics to the complex frailty syndrome and identify motor unit remodelling as a possible contributing factor.
Fluid–Structure Interaction and In Vitro Analysis of a Real Bileaflet Mitral Prosthetic Valve to Gain Insight Into Doppler-Silent Thrombosis
Authors: Dimasi Annalisa , Piloni Daniela , Spreafico Laura , Votta Emiliano , Vismara Riccardo , Fiore Gianfranco Beniamino , Meskin Masoud , Fusini Laura , Muratori Manuela , Montorsi Piero , Pepi Mauro , Redaelli Alberto
Published: May 2019

Prosthetic valve thrombosis (PVT) is a serious complication affecting prosthetic heart valves. The transvalvular mean pressure gradient (MPG) derived by Doppler echocardiography is a crucial index to diagnose PVT but may result in false negatives mainly in case of bileaflet mechanical valves (BMVs) in mitral position. This may happen because MPG estimation relies on simplifying assumptions on the transvalvular fluid dynamics or because Doppler examination is manual and operator dependent. A deeper understanding of these issues may allow for improving PVT diagnosis and management. To this aim, we used in vitro and fluid–structure interaction (FSI) modeling to simulate the function of a real mitral BMV in different configurations: normally functioning and stenotic with symmetric and completely asymmetric leaflet opening, respectively. In each condition, the MPG was measured in vitro, computed directly from FSI simulations and derived from the corresponding velocity field through a Doppler-like postprocessing approach. Following verification versus in vitro data, MPG computational data were analyzed to test their dependency on the severity of fluid-dynamic derangements and on the measurement site. Computed MPG clearly discriminated between normally functioning and stenotic configurations. They did not depend markedly on the site of measurement, yet differences below 3 mmHg were found between MPG values at the central and lateral orifices of the BMV. This evidence suggests a mild uncertainty of the Doppler-based evaluation of the MPG due to probe positioning, which yet may lead to false negatives when analyzing subjects with almost normal MPG.
Probabilistic Analysis of Bifurcations in Stochastic Nonlinear Dynamical Systems
Authors: Mirzakhalili Ehsan , Epureanu Bogdan I.
Published: May 2019

Bifurcation diagrams are limited most often to deterministic dynamical systems. However, stochastic dynamics can substantially affect the interpretation of such diagrams because the deterministic diagram often is not simply the mean of the probabilistic diagram. We present an approach based on the Fokker-Planck equation (FPE) to obtain probabilistic bifurcation diagrams for stochastic nonlinear dynamical systems. We propose a systematic approach to expand the analysis of nonlinear and linear dynamical systems from deterministic to stochastic when the states or the parameters of the system are noisy. We find stationary solutions of the FPE numerically. Then, marginal probability density function (MPDF) is used to track changes in the shape of probability distributions as well as determining the probability of finding the system at each point on the bifurcation diagram. Using MPDFs is necessary for multidimensional dynamical systems and allows direct visual comparison of deterministic bifurcation diagrams with the proposed probabilistic bifurcation diagrams. Hence, we explore how the deterministic bifurcation diagrams of different dynamical systems of different dimensions are affected by noise. For example, we show that additive noise can lead to an earlier bifurcation in one-dimensional (1D) subcritical pitchfork bifurcation. We further show that multiplicative noise can have dramatic changes such as changing 1D subcritical pitchfork bifurcations into supercritical pitchfork bifurcations or annihilating the bifurcation altogether. We demonstrate how the joint probability density function (PDF) can show the presence of limit cycles in the FitzHugh–Nagumo (FHN) neuron model or chaotic behavior in the Lorenz system. Moreover, we reveal that the Lorenz system has chaotic behavior earlier in the presence of noise. We study coupled Brusselators to show how our approach can be used to construct bifurcation diagrams for higher dimensional systems.
Experimental Heat Transfer From Heating Source Subjected to Rigorous Natural Convection Inside Enclosure and Cooled by Forced Nanofluid Flow
Authors: Esmaeil Khaled Khodary , Sultan Gamal I. , Al-Mufadi Fahad A. , Almasri Radwan A.
Published: May 2019

Mixed convection heat transfer characteristics from heat source located symmetrically inside square enclosure and cooled by Al2O3/water-based nanofluid flow was experimentally investigated. The configuration was subjected to high levels of natural convection and low rates of nanofluid flow. The nanofluid thermophysical properties were characterized using the available correlations in the literatures except the viscosity which was measured and correlated in terms of the nanoparticles loading ratios. Comparative analysis indicated that the application of nanofluid could not guarantee heat transfer enhancement in configurations dominated by natural convection. Exception heat transfer enhancement was only found when very low nanoparticles loading ratio was applied. Instead, heat transfer degradation was found especially in the cases of highest nanoparticles loading ratios. Alternatively, heat transfer enhancement was observed when the forced convection effect was substantial at the highest nanofluid flow rate. The present conclusions were justified and correlated to the findings reported in the literature.
Heat Transfer and Turbulent Flow Structure in Channels With Miniature V-Shaped Rib-Dimple Hybrid Structures on One Wall
Authors: Zhang Peng , Rao Yu , Li Yanlin , Weigand Bernhard
Published: May 2019

An experimental and numerical study has been conducted on heat transfer and turbulent flow structure in channels with novel hybrid structures with miniature V-shaped ribs and dimples on one wall. One miniature V-shaped rib was arranged immediately upstream each individual dimple to form the hybrid structure, which aims at inducing additional near-wall secondary flow interacting with the dimple vortex flow and further improving the heat transfer. Steady-state convective heat transfer experiments were done to obtain the heat transfer and pressure loss of the turbulent flow over the surfaces with the miniature V rib-dimples for the Reynolds numbers from 18,700 to 60,000. In addition, the turbulent flow structure in the V rib-dimpled channels has been predicted by carrying out numerical computations. The experimental results indicated that the overall heat transfer enhancement of the miniature V rib-dimpled channels can be increased by up to about 60.0% compared with the counterpart of the dimpled only channel, and by about 23.0% compared with the counterpart of the miniature V ribbed only channel. The miniature V ribs showed appreciable effects on the heat transfer and pressure loss characteristics for the turbulent flow over the V rib-dimpled surfaces. The numerical computations showed that the miniature V rib upstream each dimple produced strong near-wall downwashing secondary flow, which significantly changed the flow patterns and intensified the turbulent flow mixing inside and outside the dimple and above the surrounding wall. These unique near-wall flow characteristics generated a significant heat transfer improvement in both the magnitude and the uniformity.
Augmented Single Loop Single Vector Algorithm Using Nonlinear Approximations of Constraints in Reliability-Based Design Optimization
Authors: Lind Petter N. , Olsson Mårten
Published: May 2019

Reliability-based design optimization (RBDO) aims at minimizing a function of probabilistic design variables, given a maximum allowed probability of failure. The most efficient methods available for solving moderately nonlinear problems are single loop single vector (SLSV) algorithms that use a first-order approximation of the probability of failure in order to rewrite the inherently nested structure of the loop into a more efficient single loop algorithm. The research presented in this paper takes off from the fundamental idea of this algorithm. An augmented SLSV algorithm is proposed that increases the rate of convergence by making nonlinear approximations of the constraints. The nonlinear approximations are constructed in the following way: first, the SLSV experiments are performed. The gradient of the performance function is known, as well as an estimate of the most probable failure point (MPP). Then, one extra experiment, a probe point, per performance function is conducted at the first estimate of the MPP. The gradient of each performance function is not updated but the probe point facilitates the use of a natural cubic spline as an approximation of an augmented MPP estimate. The SLSV algorithm using probing (SLSVP) also incorporates a simple and effective move limit (ML) strategy that also minimizes the heuristics needed for initiating the optimization algorithm. The size of the forward finite difference design of experiment (DOE) is scaled proportionally with the change of the ML and so is the relative position of the MPP estimate at the current iteration. Benchmark comparisons against results taken from the literature show that the SLSVP algorithm is more efficient than other established RBDO algorithms and converge in situations where the SLSV algorithm fails.
Self-Forcing Mechanism of the Braided Tube as a Robotic Gripper
Authors: Shang Zufeng , Ma Jiayao , Li Jinhua , Zhang Zemin , Zhang Guokai , Wang Shuxin
Published: May 2019

Robotic grippers, which act as the end effector and contact the objects directly, play a crucial role in the performance of the robots. In this paper, we design and analyze a new robotic gripper based on the braided tube. Apart from deployability, a self-forcing mechanism, i.e., the holding force increases with load/object weight, facilitates the braided tube as a robotic gripper to grasp objects with different shapes, weights, and rigidities. First, taking a cylindrical object as an example, the self-forcing mechanism is theoretically analyzed, and explicit formulas are derived to estimate the holding force. Second, experimental and numerical analyses are also conducted for a more detailed understanding of the mechanism. The results show that a holding force increment by 120% is achieved due to self-forcing, and the effects of design parameters on the holding force are obtained. Finally, a braided gripper is fabricated and operated on a KUKA robot arm, which successfully grasps a family of objects with varying shapes, weights, and rigidities. To summarize, the new device shows great potentials for a wide range of engineering applications where properties of the objects are varied and unpredictable.
An Experimentally Derived Model to Predict the Water Film in a Compressor Cascade With Droplet Laden Flow
Authors: Neupert Niklas , Harbeck Janneck Christoph , Joos Franz
Published: May 2019

In recent years, overspray fogging has become a powerful means for power augmentation of industrial gas turbines. Despite the positive thermodynamic effect on the cycle, droplets entering the compressor increase the risk of water droplet erosion and deposition of water on the blades leading to an increase of required torque and profile loss. Due to this, detailed information about the structure and the amount of water on the surface is key for compressor performance. Experiments were conducted with a droplet laden flow in a transonic compressor cascade focusing on the film formed by the deposited water. Two approaches were taken. In the first approach, the film thickness on the blade was directly measured using white light interferometry. Due to significant distortion of the flow caused by the measurement system, a transfer of the measured film thickness to the undisturbed case is not possible. Therefore, a film model is adapted to describe the film flow in terms of height averaged film parameters. In the second approach, experiments were conducted in an undisturbed cascade setup and the water film pattern was measured using a nonintrusive quantitative image processing tool. Utilizing the measured flow pattern in combination with findings from the literature, the rivulet flow structure is resolved. From continuity of the water flow, a film thickness is derived showing good agreement with the previously calculated results. Using both approaches, a three-dimensional (3D) reconstruction of the water film pattern is created giving first experimental results of the film forming on stationary compressor blades under overspray fogging conditions.
A new record of Ornithodoros (Pavlovskyella) verrucosus (Acari: Argasidae) from a porcupine burrow in western Iran
Authors: Hosseini Chegeni Asadollah , Tavakoli Majid , Koshki Habibollah , Khedri Javad , Kayedi Mohammad Hassan
Published: May 2019

We found an Ornithodoros species with distinct morphological characteristics than Alveonasus genus and other O. (Pavlovskyella) species group. Tick specimens were collected from a porcupine burrow, located in Lorestan province, western Iran. Genomic DNA of tick was extracted using CTAB and then three gene fragments of cytochrome oxidase subunit I (COI) and 16S mtDNA & 18S rDNA were amplified by PCR. Tick specimens were identified as near to O. (P.) verrucosus and O. (P.) tholozani. So the identification was confirmed by BLAST analysis of 16S mtDNA & 18S rDNA and COI gene fragments. A taxonomic key to the native adult subfamily Ornithodorinae species of Iran are provided to facilitate their identification.
Antibiotic Susceptibility of Escherichia coli Cells during Early-Stage Biofilm Formation
Authors: Gu Huan , Lee Sang Won , Carnicelli Joseph , Jiang Zhaowei , Ren Dacheng
Published: May 2019

Mature biofilms are known for their high-level tolerance to antibiotics; however, antibiotic susceptibility of sessile cells during early-stage biofilm formation is not well understood. In this study, we aim to fill this knowledge gap by following bacterial antibiotic susceptibility during early-stage biofilm formation. We found that the attached cells have a dynamic change in antibiotic susceptibility, and during certain phases, they can be more sensitive to antibiotics than planktonic counterparts in the same culture. Using surface chemistry-controlled patterned biofilm formation, cell-surface and cell-cell interactions were found to affect the antibiotic susceptibility of attached cells. Collectively, these findings provide new insights into biofilm physiology and reveal how adaptation to the attached life form may influence antibiotic susceptibility of bacterial cells.
MICU1 and MICU2 Play an Essential Role in Mitochondrial Ca
2+
Uptake, Growth, and Infectivity of the Human Pathogen Trypanosoma cruzi
Authors: Bertolini Mayara S. , Chiurillo Miguel A. , Lander Noelia , Vercesi Anibal E. , Docampo Roberto
Published: May 2019

Trypanosoma cruzi
is the etiologic agent of Chagas disease and belongs to the early-branching eukaryotic supergroup Excavata. Its mitochondrial calcium uniporter (MCU) subunit shares similarity with the animal ortholog that was important to discover its encoding gene. In animal cells, the MICU1 and MICU2 proteins act as Ca
2+
sensors and gatekeepers of the MCU, preventing Ca
2+
uptake under resting conditions and favoring it at high cytosolic Ca
2+
concentrations ([Ca
2+
]
cyt
). Using the CRISPR/Cas9 technique, we generated
TcMICU1
and
TcMICU2
knockout cell lines and showed that MICU1 and -2 do not act as gatekeepers at low [Ca
2+
]
cyt
but are essential for normal growth, host cell invasion, and intracellular replication, revealing lineage-specific adaptations.
Nontypeable
Haemophilus influenzae
Has Evolved Preferential Use of
N-
Acetylneuraminic Acid as a Host Adaptation
Authors: Ng Preston S. K. , Day Christopher J. , Atack John M. , Hartley-Tassell Lauren E. , Winter Linda E. , Marshanski Tal , Padler-Karavani Vered , Varki Ajit , Barenkamp Stephen J. , Apicella Michael A. , Jennings Michael P.
Published: May 2019

Host-adapted bacterial pathogens such as NTHi cannot survive out of their host environment and have evolved host-specific mechanisms to obtain nutrients and evade the immune response. Relatively few of these host adaptations have been characterized at the molecular level. NTHi utilizes sialic acid as a nutrient and also incorporates this sugar into LOS, which is important in biofilm formation and immune evasion. In the present study, we showed that NTHi has evolved to preferentially utilize the Neu5Ac form of sialic acid. This adaptation is due to the substrate preference of the enzyme CMP-Neu5Ac synthetase, which synthesizes the activated form of Neu5Ac for macromolecule biosynthesis. This adaptation allows NTHi to evade killing by a human antibody response against the nonhuman sialic acid Neu5Gc.
Antimicrobial Peptides, Polymorphic Toxins, and Self-Nonself Recognition Systems in Archaea: an Untapped Armory for Intermicrobial Conflicts
Authors: Makarova Kira S. , Wolf Yuri I. , Karamycheva Svetlana , Zhang Dapeng , Aravind L. , Koonin Eugene V.
Published: May 2019

Diverse and highly variable systems involved in biological conflicts and self-versus-nonself discrimination are ubiquitous in bacteria but much less studied in archaea. We performed comprehensive comparative genomic analyses of the archaeal systems that share components with analogous bacterial systems and propose an approach to identify new systems that could be involved in these functions. We predict polymorphic toxin systems in 141 archaeal genomes and identify new, archaea-specific toxin and immunity protein families. These systems are widely represented in archaea and are predicted to play major roles in interactions between species and in intermicrobial conflicts. This work is expected to stimulate experimental research to advance the understanding of poorly characterized major aspects of archaeal biology.
Microbiomes, Community Ecology, and the Comparative Method
Authors: Hird Sarah M.
Published: May 2019

Microbiomes contain many levels of biological information, and integrating across the levels creates a holistic understanding of host-microbiome interactions. In my research on the evolution and ecology of avian microbiomes, I use two complementary frameworks: the microbiome as a community and the microbiome as a trait of the host.
Association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder: US-based retrospective cohort study
Authors: Szabo Shelagh M , Gooch Katherine , Schermer Carol , Walker David , Lozano-Ortega G , Rogula Basia , Deighton Alison , Vonesh Edward , Campbell Noll
Published: May 2019

Objective

To estimate the association between cumulative anticholinergic burden and falls and fractures in patients with overactive bladder (OAB).

Design

A retrospective claims-based study (2007–2015) of patients with OAB; outcomes from a subset were contrasted to a non-OAB comparison.

Setting

United States, commercially and Medicare-insured population.

Participants

154 432 adults with OAB and 86 966 adults without OAB, mean age of 56 years, and 67.9% women.

Main outcome measures

Cumulative anticholinergic burden, a unitless value representing exposure over time, was estimated over the 12 months pre-index (‘at baseline’) and every 6 months post index. Burden was categorised as no burden (0), low burden (1–89), medium burden (90–499) or high burden (500+). Unadjusted rates of falls or fractures were estimated, and the increased risk associated with anticholinergic burden (measured at the closest 6-month interval prior to a fall or fracture) was assessed using a Cox proportional hazards model and a marginal structural model.

Results

Median (IQR) baseline anticholinergic burden was 30 (0.0–314.0) and higher among older (≥65 years, 183 [3.0–713.0]) versus younger (<65 years, 13 [0.0–200.0]) adults. The unadjusted rate of falls or fractures over the period was 5.0 per 100 patient-years, ranging from 3.1 (95% CI 3.0–3.2) for those with no burden, to 7.4 (95% CI 7.1–7.6) for those with high burden at baseline. The adjusted risk of falls and fractures was greater with higher anticholinergic burden in the previous 6 months, with an HR of 1.2 (95% CI 1.2 to 1.3) for low burden versus no burden, to 1.4 (95% CI 1.3 to 1.4) for high versus no burden. Estimates from marginal structural models adjusting for time-varying covariates were lower but remained significantly higher with a higher anticholinergic burden. Rates of falls and fractures were approximately 40% higher among those with OAB (vs those without).

Conclusion

Higher levels of anticholinergic burden are associated with higher rates of falls and fractures, highlighting the importance of considering anticholinergic burden when treating patients with OAB.
Equal treatment efficacy of direct-acting antivirals in patients with chronic hepatitis C and hepatocellular carcinoma? A prospective cohort study
Authors: Huang Chung-Feng , Yeh Ming-Lun , Huang Ching-I , Liang Po-Cheng , Lin Yi-Hung , Hsieh Ming-Yen , Wei Yu-Ju , Lin Zu-Yau , Chen Shinn-Cherng , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long , Yu Ming-Lung
Published: May 2019

Objective

The treatment outcome of direct-acting antivirals (DAAs) in chronic hepatitis C patients with hepatocellular carcinoma (HCC) is controversial. The current study aimed to address the treatment efficacy and safety of DAAs in patients with curative or active HCC, compared with those of patients without HCC.

Design

A prospective cohort study

Setting

A medical centre and two regional hospitals in Taiwan

Participants

A total of 713 Taiwanese patients (601 non-HCC, 74 curative HCC and 38 active HCC patients) who received standard-of-care DAAs were consecutively enrolled in the study.

Main outcome measurement

The primary objective was to determine treatment efficacy, defined as undetectable hepatitis C virus RNA throughout 12 weeks of the post-treatment follow-up period (sustained virological response 12 [SVR12]).

Results

The overall SVR12 rate was 96.9%. The SVR12 rate was similar between the patients with HCC and those without HCC (95.5% vs 97.2%, p=0.37). The HCC patients were divided into two groups, those with curative HCC and those with viable HCC; a substantially but not significantly lower SVR rate, 92.1% (35/38), was observed in the patients with viable HCC compared with the SVR rate, 97.3% (72/74), in those with curative HCC (p=0.33). Compared with the patients with curative HCC, the patients with viable HCC had a significantly higher proportion of serious adverse events (10.5% vs 1.0%, p=0.002), early treatment discontinuation (10.5% vs 2.8%, p=0.03) and mortality (5.3% vs 0.1%, p=0.008).

Conclusions

An equivalently high SVR rate was observed in patients with either past or active HCC compared with those without HCC. The safety concerns in the HCC patients did not compromise treatment efficacy.
Phase I open-label trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases (IPGP study): study protocol
Authors: Vatandoust Sina , Bright Tim , Roy Amitesh Chandra , Watson David , Gan Susan , Bull Jeff , Abbas Muhammad Nazim , Karapetis Christos Stelios
Published: May 2019

Introduction

Gastric cancer with peritoneal metastasis has a poor outcome. Only a few studies have specifically investigated this group of patients. Japanese researchers have shown that chemotherapy with intraperitoneal paclitaxel (IPP) and oral S-1 (tegafur/gimeracil/oteracil) is active and well tolerated. These results have been achieved in a specific genetic pool (Japanese population), using regimens that may not be available in other parts of the world. We have designed this phase I trial to investigate IPP in combination with a standard chemotherapy combination in these patients.

Methods

We use a 3+3 expanded cohort dose escalation until a predefined number of dose-limiting toxicities are reached. Patients will have an intraperitoneal catheter placed surgically after trial enrolment. Chemotherapy includes a maximum of six cycles (21 days) of capecitabine (X) (1000 mg/m2two times a day, days 1–14)+cisplatin (C) (intravenous 80 mg/m2day 1) and IPP (days 1 and 8) with the following doses: cohort-1: 10 mg/m2, cohort-2: 20 mg/m2and cohort-3: 30 mg/m2. Primary endpoint is to determine the maximum tolerated dose of IPP. Secondary endpoints include determining the safety and tolerability of IPP in combination with C and X, overall response rates, ascites response rate, progression-free survival, overall survival and effects on quality of life.

Important inclusion criteria include age ≥18 years, human epidermal growth factor receptor 2 non-amplified gastric adenocarcinoma with histological or cytology-proven peritoneal involvement and adequate organ function. Exclusion criteria include previous malignancy within 5 years, recent abdominal or pelvic radiation treatment, significant abdominal adhesions or sepsis.

Ethics and dissemination

The study is approved by Southern Adelaide Clinical Human Research Ethics Committee. A manuscript will be prepared for publication on the completion of the trial. This study will be conducted according to the Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) annotated with TGA comments (Therapeutic Goods Administration DSEB July 2000) and in compliance with applicable laws and regulations. The study will be performed in accordance with the NHMRC Statement on Ethical Conduct in Research Involving Humans (© Commonwealth of Australia 2007), and the NHMRC Australian Code for the Responsible Conduct of Research (©Australian Government 2007), and the principles laid down by the World Medical Assembly in the Declaration of Helsinki 2008.

Trial registration number

ACTRN12614001063606.
Intramedullary nails versus distal locking plates for fracture of the distal femur: results from the Trial of Acute Femoral Fracture Fixation (TrAFFix) randomised feasibility study and process evaluation
Authors: Griffin Xavier L , Costa Matthew L , Phelps Emma , Parsons Nicholas , Dritsaki Melina , Achten Juul , Tutton Elizabeth , Lerner Robin Gillmore , McGibbon Alwin , Baird Janis
Published: May 2019

Objectives

This feasibility study and process evaluation assessed the likely success of a definitive trial of intramedullary fixation with locked retrograde nails versus extramedullary fixation with fixed angle plates for fractures of the distal femur.

Design & setting

A multicentre, parallel, two-arm, randomised controlled feasibility study with an embedded process evaluation was conducted at seven NHS hospitals in England. Treatment was randomly allocated in 1:1 ratio, stratified by centre and chronic cognitive impairment. Participants, but not surgeons or research staff, were blinded to the allocation.

Participants

Patients 18 years and older with a fracture of the distal femur, who their surgeon believed would benefit from internal fixation, were eligible to take part.Participants were allocated to receive either a retrograde intramedullary nail or an anatomical locking plate.

Outcomes

The primary outcomes for this feasibility study were the recruitment rate and completion rate of the EQ-5D-5L at 4 months post-randomisation. Baseline characteristics, disability rating index, quality of life scores, measurements of social support and self-efficacy, resource use and radiographic assessments were also collected. The views of patients and staff were collected during interviews.

Results

Recruitment and data completion were lower than expected. 23 of 82 eligible patients were recruited (nail, 11; plate, 12). The recruitment rate was estimated as 0.42 (95% CI 0.27 to 0.62) participants per centre-month. Data completeness of the EQ-5D-5L at 4 months was 61 per cent (95% CI 43% to 83%). The process evaluation demonstrated that the main barriers to recruitment were variation in treatment pathways across centres, lack of surgeon equipoise and confidence in using both interventions and newly formed research cultures that lacked cohesion.

Conclusions

A modified trial design, with embedded recruitment support intervention, comparing functional outcome in cognitively intact adults who have sustained a fragility fracture of the distal femur is feasible.

Ethics approval

The Wales Research Ethics Committee 5 approved the study (ref: 16/WA/0225).

Trial registration number

ISRCTN92089567; Pre-results.
Burnout as a correlate of depression among medical students in Cameroon: a cross-sectional study
Authors: Njim Tsi , Mbanga Clarence Mvalo , Tindong Maxime , Fonkou Steve , Makebe Haman , Toukam Louise , Fondungallah Johnson , Fondong Azingala , Mulango Isabelle , Kika Belmond
Published: May 2019

Objective

Burnout syndrome has been shown to mediate the pathway between job stress and depression. This study aims to assess the relationship between the various components of burnout syndrome and depression; and to determine the contribution of other sociodemographic variables to depression among medical students in Cameroon.

Design

A cross-sectional study.

Setting

Three of the five medical schools in Cameroon with students in both preclinical and clinical levels of studies.

Participants

The study included 413 consenting medical students.

Primary outcome measure

Data were collected via a printed self-administered questionnaire. The primary outcome—depression was assessed using the Patient Health Questionnaire–9 (PHQ-9). Burnout was assessed using the Oldenburg Burnout Inventory. Multivariable linear regression was used to identify independent correlates of depression.

Results

The overall prevalence of depression (PHQ-9 >4) and major depressive disorder (PHQ-9 >9) in these students was 66.34% and 23.00%, respectively. After multivariable linear regression analysis, four variables—total OLBI (beta=0.32; 95% CI 0.22 to 0.42; p<0.001); number of children (beta=−2.26; 95% CI −3.70 to –0.81; p=0.002); occurrence of a life-changing crises (beta=1.29; 95% CI 0.13 to 2.45; p=0.029) and presence of a chronic illness (beta=3.19; 95% CI 0.96 to 5.42; p=0.005) significantly predicted depression in these students and explained 32.4% of the variance (R2=32.4, F[14, 204]=6.98, p<0.001). The emotional exhaustion component (R2=17.4, F[1, 411]=86.39, p<0.001) explained more of the variance in depression than the disengagement component (R2=6.1, F[1, 411]=26.76, p<0.001) of burnout syndrome.

Conclusion

The prevalence of depression among medical students in Cameroon is high. It is important that correlates of depression are identified early in medical students to limit progress to depression.
Care of general practice patients preceding and following a suicide attempt: observational study in Flemish general practices
Authors: Boffin Nicole , Van Casteren Viviane , De Ridder Karin
Published: May 2019

Objectives

First, to examine general practitioner (GP) knowledge about the care (needs) of their patients; second, to examine the quality of GP follow-up care; third, to examine the transmission of patient care information from hospitals/emergency services (ES) to GPs.

Setting

105 general practices from the representative Belgian Network of Sentinel General Practices (SGP) in Flanders, the largest region of Belgium, during 2013–2016.

Participants

245 suicide attempts by regular patients.

Outcomes measures

Ten care-related measures, including three indicators of quality of follow-up care, were based on data reported by the SGP on structured forms at baseline and at two follow-up points in time.

Results

As for GP knowledge, 10.5% of SGP failed to report whether suicidal risk was noticed in patients seen in the month preceding the attempt; 9.0% whether there were previous attempts; 22.5% whether the patient was receiving mental health treatment at follow-up and 22.0% whether suicidal behaviour was repeated at follow-up. Relatively more patients≥65 years had no suicide risk evaluation (OR 3.54; 95% CI 1.11 to 11.26). As for quality of follow-up care, there was a GP–patient contact following 90.5% of the attempts, follow-up appointments were planned following 43.4% of the attempts and there was a GP contact with patient proxies following 62.8% of the attempts. Patient age ≥65 years (OR 4.09; 95% CI 1.79 to 9.33), a recent GP–patient contact preceding the attempt (OR 1.97; 95% CI 1.13 to 3.43), depression of patient (OR 1.96; 95% CI 1.14 to 3.37) and a suburban SGP area (OR 2.34; 95% CI 1.13 to 4.82) were determinants of an increased quality of care sum. GPs received patient care information from a hospital (ES) for 67.8% of eligible attempts, with SGP practice location being a determinant.

Conclusions

GPs are highly involved in the care of suicide attempters but there is room for improvement, also in informational continuity from hospital (ES) to GPs.
How incremental video training did not guarantee implementation due to fluctuating population prevalence
Authors: Vink Peter , Torensma Bart , Lucas Cees , Hollmann Markus W , van Schaik Ivo N , Vermeulen Hester
Published: May 2019

Patients with stroke admitted at the neurology/neurosurgery ward of the Academic Medical Centre in Amsterdam, The Netherlands, may experience problems in communication, such as aphasia, severe confusion/delirium or severe language barriers. This may prevent self-reported pain assessment; therefore, pain behaviour observation scales are needed. In this project, we therefore aimed to implement the Rotterdam Elderly Pain Observation Scale (REPOS) by video training.

We used a stepped-wedge cluster design with clusters of four to five nurses with intervals of 2 weeks, for a total study duration of 34 weeks. Primary endpoint was the proportion of shifts in which nurses used the REPOS when caring for an eligible patient. A questionnaire was send biweekly to assess self-perceived competence and attitude on pain measurement in patients able or unable to self-report pain intensity. No other strategies were used to promote the use of the REPOS.

Though the proportion of shifts in which trained nurses cared for eligible patients increased from 0% at baseline to 83% at the end of the study, the proportion of cumulative shifts where the REPOS was used decreased from 14% to 6%, respectively. Process evaluation suggests that this decrease can (in part) be attributed to low and varying prevalence of eligible patients and opportunities for practice. In total, 24 (45.3%) nurses had used the REPOS at least once after 34 weeks, with a median of two times (1–33). Nurses perceived themselves 'competent' to 'very competent' in pain behaviour observation. There was no negative attitude towards pain measurement.

This study shows that education alone may not be effective when implementing a pain behaviour observation scale for non-communicative patients with Acquired Brain Injury. Individual motivation of health professionals and individual patient factors may be of influence for the use of the REPOS.
Combined association of key risk factors on ischaemic outcomes and bleeding in patients with myocardial infarction
Authors: Lindholm Daniel , Sarno Giovanna , Erlinge David , Svennblad Bodil , Hasvold Lars Pål , Janzon Magnus , Jernberg Tomas , James Stefan K
Published: May 2019

Objective

In patients with myocardial infarction (MI), risk factors for bleeding and ischaemic events tend to overlap, but the combined effects of these factors have scarcely been studied in contemporary real-world settings. We aimed to assess the combined associations of established risk factors using nationwide registries.

Methods

Using the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry, patients with invasively managed MI in 2006–2014 were included. Six factors were assessed in relation to cardiovascular death (CVD)/MI/stroke, and major bleeding: age ≥65, chronic kidney disease, diabetes, multivessel disease, prior bleeding and prior MI.

Results

We studied 100 879 patients, of whom 20 831 (20.6%) experienced CVD/MI/stroke and 5939 (5.9%) major bleeding, during 3.6 years median follow-up. In adjusted Cox models, all factors were associated with CVD/MI/stroke, and all but prior MI were associated with major bleeding. The majority (53.5%) had ≥2 risk factors. With each added risk factor, there was a marked but gradual increase in incidence of the CVD/MI/stroke. This was seen also for major bleeding, but to a lesser extent, largely driven by prior bleeding as the strongest risk factor.

Conclusions

The majority of patients with MI had two or more established risk factors. Increasing number of risk factors was associated with higher rate of ischaemic events. When excluding patients with prior major bleeding, bleeding incidence rate increased only minimally with increasing number of risk factors. The high ischaemic risk in those with multiple risk factors highlights an unmet need for additional preventive measures.
Serum long-chain omega-3 fatty acids, hair mercury and exercise-induced myocardial ischaemia in men
Authors: Tajik Behnam , Tuomainen Tomi-Pekka , Kurl Sudhir , Salonen Jukka , Virtanen Jyrki K
Published: May 2019

Objective

Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish have been inversely associated with coronary heart disease (CHD) risk. Fish may also contain methylmercury, which has been associated with higher CHD risk and may diminish the cardioprotective effect of long-chain omega-3 PUFA. We investigated the associations of serum long-chain omega-3 PUFA and hair mercury with the odds for myocardial ischaemia during exercise.

Methods

A total of 2199 men from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 years were studied in 1984–89. Of the 2199 men, 342 had history of CHD. The men performed a maximal symptom-limited exercise stress test using an electrically braked bicycle ergometer. ORs for exercise-induced myocardial ischaemia were estimated with logistic regression.

Results

In the multivariable analysis, those in the highest versus lowest serum long-chain omega-3 PUFA quartile had 33% lower odds of myocardial ischaemia (OR 0.67, 95% CI 0.51 to 0.87, p-trend=0.006). The association was stronger among those with CHD history (OR 0.10, 95% CI 0.03 to 0.39, p-trend <0.001), than among those without (OR 0.80, 95% CI 0.57 to 1.12, p-trend=0.17) (p-interaction=0.01). Higher hair mercury concentration was associated with increased odds for myocardial ischaemia in the entire population (OR 1.62, 95% CI 1.22 to 2.14, p-trend=0.002).

Conclusion

Higher circulating concentrations of the long-chain omega-3 PUFAs, a marker for fish consumption, were associated with lower occurrence of exercise-induced myocardial ischaemia, but only among men with CHD history. Hair mercury concentration was directly associated with the occurrence of exercise-induced myocardial ischaemia in the entire study population.