bluuebunny/crossref_metadata_2025 huggingface dataset:
PSMC (pairwise sequentially Markovian coalescent) analysis of RAD (restriction site associated DNA) sequencing data
Authors: Liu Shenglin , Hansen Michael M.
Published: October 2016

The pairwise sequentially Markovian coalescent (PSMC) method uses the genome sequence of a single individual to estimate demographic history covering a time span of thousands of generations. Although originally designed for whole‐genome data, we here use simulations to investigate its applicability to reference genome‐aligned restriction site associated DNA (RAD) data. We find that RAD data can potentially be used for PSMC analysis, but at present with limitations. The key factor is the proportion (p) of the genome that the RAD data covers. In our simulations, a proportion of 10% can still retain a substantial amount of coalescent information, whereas for 1% estimation becomes unreliable. The performance depends strongly on mutation rate (μ) and recombination rate (r) and is proportional to μ*p/r. When the value of this term is low, increasing the amount of data and number of iterations helps restoring the power of the estimation. We subsequently analyse one whole‐genome‐sequenced and 17 RAD‐sequenced three‐spined sticklebacks (Gasterosteus aculeatus) from a lake in Greenland. The whole‐genome sequence suggests a relatively recent expansion and decline within ca. 4000–40 000 generations ago, possibly reflecting postglacial expansion and founding of the lake population. RAD data, where chromosomes from 10 individuals are combined, identify a similar pattern. Our study provides guidance about the use of PSMC analysis and suggests measures that can improve its utility for RAD data. Finally, the study shows that RAD loci in general contain coalescent information that can be used for developing more targeted methods.
RNA‐Seq identifies redox balance related gene expression alterations under acute cadmium exposure in yeast
Authors: Huang Xinhe , Li Yuxing , Pan Jingmei , Li Ming , Lai Yongqin , Gao Jie , Li Xueru
Published: October 2016

The nonessential metal cadmium can cause cell toxicity and is associated with a range of human diseases including cardiovascular diseases, neurodegenerative diseases and cancers. In this study, cadmium‐induced global gene expression profile of yeast was obtained using RNA Sequencing (RNA‐Seq) and further analyzed by means of informatics and experiments. A total of 912 Differentially Expressed Genes (DEGs) (FDR of q < 0.01), including 415 Cd‐inducible and 497 Cd‐repressed genes were identified. Based on the DEGs, 25 cadmium responsive Clusters of Orthologous Group (COG) and three types of cadmium‐induced Gene Ontology (GO) including cellular components, molecular functions and biological processes were analyzed in details. Thereafter, 79 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways under cadmium exposure were assigned. Collectively, 108 redox balance related genes were extracted under cadmium exposure. Meanwhile, cadmium exposure lowered cellular Mitochondrial Membrane Potential (MMP) and increased Reactive Oxygen Species (ROS) levels significantly in the context of mitochondrial dysfunction. Furthermore, cadmium exposure increased cellular GSH levels and decreased GSSG levels and also lowered GSSG/GSH ratio of cells, which supports experimentally our claim that the redox balance is the primary mechanism for cadmium toxicity. The results present in this study may provide new strategies for cadmium detoxification and prevention or therapies of cadmium‐associated diseases.
Two‐current choice flumes for testing avoidance and preference in aquatic animals
Authors: Jutfelt Fredrik , Sundin Josefin , Raby Graham D. , Krång Anna‐Sara , Clark Timothy D.
Published: October 2016

Aquatic chemical ecology is an important and growing field of research that involves understanding how organisms perceive and respond to chemical cues in their environment. Research assessing the preference or avoidance of a water source containing specific chemical cues has increased in popularity in recent years, and a variety of methods have been described in the scientific literature. Two‐current choice flumes have seen the greatest increase in popularity, perhaps because of their potential to address the broadest range of research questions.

Here, we review the literature on two‐current choice flumes and show that there is a clear absence of standardized methodologies that make comparisons across studies difficult. Some of the main issues include turbulent flows that cause mixing of cues, inappropriate size of choice arenas for the animals, short experiments with stressed animals, failure to report how experiment and researcher biases were eliminated, general underreporting of methodological details, underutilization of collected data and inappropriate data analyses.

In this review, we present best practice guidelines on how to build, test and use two‐current choice flumes to measure the behavioural responses of aquatic animals to chemical cues, and provide blueprints for flume construction. The guidelines include steps that can be taken to avoid problems commonly encountered when using two‐current choice flumes and analysing the resulting data.

This review provides a set of standards that should be followed to ensure data quality, transparency and replicability in future studies in this field.
Mechanistic description of population dynamics using dynamic energy budget theory incorporated into integral projection models
Authors: Smallegange Isabel M. , Caswell Hal , Toorians Marjolein E. M. , de Roos André M.
Published: October 2016

Integral projection models (IPMs) provide a powerful approach to investigate ecological and rapid evolutionary change in quantitative life‐history characteristics and population dynamics. IPMs are constructed from functions that describe the demographic rates – survival, growth and reproduction – in relation to the characteristics of individuals and their environment. Currently, however, demographic rates are estimated using phenomenological regression models that lack a mechanistic representation of the biological processes that give rise to observed demographic variation. This lack of mechanistic underpinning limits the ability of the model to predict future dynamics under novel environmental conditions because the model ingredients pertain to current environmental conditions only.

Here, we use dynamic energy budget (DEB) theory to construct DEB‐IPMs based on a mechanistic representation of individual life‐history trajectories. We derive the demographic functions describing growth and reproduction from a simple DEB growth model. The functions describing mortality and the association between parent and offspring characteristics do not follow DEB theory and hence are estimated from individual‐level observations.

We apply the DEB‐IPM to two contrasting systems: the small, fast‐reproducing bulb mite Rhizoglyphus robini and the large, slow‐reproducing reef manta ray Manta alfredi. In both cases, predictions of population growth rate, lifetime reproductive success and generation time agree with empirical observations. In case of the bulb mite, predictions and observations even agree across different feeding conditions.

If the DEB energetics model is accepted as describing growth and reproduction, DEB‐IPMs can be parameterised using easy‐to‐collect life cycle information (growth rate, length at birth, maturation and old age) making them suitable for data‐deficient species. Because species differ only in these DEB parameters, comparative studies of character and population dynamics between species are straightforward, particularly since DEB‐IPMs can be extended to include population feedback on resources, of which we give an example. Most crucially, because DEB theory specifies growth and reproduction rates as explicitly dependent on environmental conditions such as food availability or temperature, DEB‐IPMs provide a mechanistic platform to investigate the biological processes that determine joint change in phenotypic characters, life‐history traits, population size and community structure.
Solo: an open source, customizable and inexpensive audio recorder for bioacoustic research
Authors: Whytock Robin C. , Christie James
Published: October 2016

Audio recorders are widely used in terrestrial and marine ecology and are essential for studying many cryptic or elusive taxa. Although several commercial systems are available, they are often expensive and are rarely user‐serviceable or easily customized.

Here, we present the Solo audio recorder. Units are constructed from the Raspberry Pi single board computer and run easy‐to‐install and freely available software. We provide an example configuration costing £167 (£83 excluding suggested memory card and battery), which records audible sound continuously for c. 40 days. We also provide a video tutorial showing hardware assembly and documentation is available via a supporting website.

The Solo recorder has been extensively field tested in temperate and tropical regions, with over 50 000 h of audio collected to date. This highly customizable and inexpensive system could greatly increase the scale and ease of conducting bioacoustic studies.
LIN‐28 balances longevity and germline stem cell number in Caenorhabditis elegans through let‐7/AKT/DAF‐16 axis
Authors: Wang Dan , Hou Lei , Nakamura Shuhei , Su Ming , Li Fang , Chen Weiyang , Yan Yizhen , Green Christopher D. , Chen Di , Zhang Hong , Antebi Adam , Han Jing‐Dong J.
Published: October 2016

The RNA‐binding protein LIN‐28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin‐28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN‐28‐regulated microRNA let‐7 was required for these effects by targeting akt‐1/2 and decreasing their protein levels. AKT‐1/2 and the downstream DAF‐16 transcription factor were both required for the lifespan and germline stem cell effects of lin‐28. The pathway also mediated dietary restriction induced lifespan extension and reduction in germline stem cell number. Thus, the LIN‐28/let‐7/AKT/DAF‐16 axis we delineated here is a program that plays an important role in balancing reproduction and somatic maintenance and their response to the environmental energy level—a central dogma of the ‘evolutionary optimization’ of resource allocation that modulates aging.
Is Alcoholics Anonymous religious, spiritual, neither? Findings from 25 years of mechanisms of behavior change research
Authors: Kelly John F.
Published: October 2016

Background

Alcoholics Anonymous (AA) is a world‐wide recovery mutual‐help organization that continues to arouse controversy. In large part, concerns persist because of AA's ostensibly quasi‐religious/spiritual orientation and emphasis. In 1990 the United States’ Institute of Medicine called for more studies on AA's effectiveness and its mechanisms of behavior change (MOBC) stimulating a flurry of federally funded research. This paper reviews the religious/spiritual origins of AA and its program and contrasts its theory with findings from this latest research.

Method

Literature review, summary and synthesis of studies examining AA's MOBC.

Results

While AA's original main text (‘the Big Book’, 1939) purports that recovery is achieved through quasi‐religious/spiritual means (‘spiritual awakening’), findings from studies on MOBC suggest this may be true only for a minority of participants with high addiction severity. AA's beneficial effects seem to be carried predominantly by social, cognitive and affective mechanisms. These mechanisms are more aligned with the experiences reported by AA's own larger and more diverse membership as detailed in its later social, cognitive and behaviorally oriented publications (e.g. Living Sober, 1975) written when AA membership numbered more than a million men and women.

Conclusions

Alcoholics Anonymous appears to be an effective clinical and public health ally that aids addiction recovery through its ability to mobilize therapeutic mechanisms similar to those mobilized in formal treatment, but is able to do this for free over the long term in the communities in which people live.
An experimental demonstration of the impact of predation on sexual segregation and primary sex ratios among ungulates
Authors: O'Kane Christopher A. J. , Macdonald David W.
Published: October 2016

Underlying mechanisms of sexual segregation among ungulates, and Trivers and Willard's hypothesis that mothers can influence primary sex ratios, continue to be topical theoretical issues. Over 2 years, using monthly repeated road transects, we determined the habitat and social segregation of male vs. female impala (Aepyceros melampus) and kudu (Tragelaphus strepsiceros) in a predator‐free, vs. a predator‐laden, South African reserve. We also determined, by the same technique but over 4 years, the primary sex ratio of the impala population free from predation. Significant overlap in habitat usage (Schoener's Index 0.63–0.8) was found between the two sexes when free from predation, but not (Schoener's Index 0.46–0.47) when under predation. While occupying the same habitats impala, kudu and wildebeest (Connochaetes taurinus) male and female groups maintained rigid social segregation throughout the year, even when at close quarters. Impala primary sex ratios were significantly biased towards females (male/female = 0.72; χ² = 4.3175, d.f. = 1, P‐value = 0.038) in the absence of predation. Our findings suggest that while risk of predation is a proximal cause of sexual segregation, thus lending support to the predator‐risk hypothesis, the underlying, functional mechanism of sexual segregation is the difference in the activity budgets of males vs. females (the activity‐budget hypothesis). Our findings also suggest that mothers may indeed be able to adjust primary sex ratios, with the postulated driver in this case being an abnormally high density of adult males.
A case of nodular subungual melanoma without Hutchinson's nail sign
Authors: Nojima Kohei , Namiki Takeshi , Tokoro Shown , Miura Keiko , Yokozeki Hiroo
Published: October 2016

An early and accurate diagnosis is critical for the optimal management of subungual melanoma; the absence of Hutchinson's nail sign makes an accurate diagnosis extremely difficult. Previous publications show that most subungual melanomas have Hutchinson's nail sign. In this report, we present a rare case of a subungual melanoma without Hutchinson's nail sign and discuss the importance of cautious evaluations of Hutchinson's nail sign by dermoscopy.
Is HLA‐E a possible genetic marker relevant for natural conception?
Authors: Gelmini Georgia Fernanda , Costa Cynthia Hernandes , Nardi Fabiola da Silva , Wowk Pryscilla Fanini , Mattar Sibelle Botogosque , Schuffner Alessandro , Bicalho Maria da Graça , Roxo Valéria Maria Munhoz Sperandio
Published: October 2016

Background

HLA‐E products, class Ib human leukocyte antigens, act in the immunology of human reproduction as modulators of the maternal immune system during pregnancy.

Aims

To evaluate HLA‐E role in the establishment of a viable pregnancy.

Materials & Methods

HLA‐E was genotyped by sequence‐based typing (SBT) and analyzed for specific polymorphisms, comparing couples who underwent assisted reproduction treatment (ART) and fertile control couples.

Results

There was a significant difference in HLA‐E allele and genotype distributions between ART couples and control couples. The allele HLA‐E*01:03 was observed in 63.2% of ART men and in 35.1% of fertile men (P = 0.0032).

Conclusion

These results suggest that HLA‐E allelic variants may play a role in the modulation of immune responses in the context of the inability of natural conception and establishment of a viable pregnancy.
New opportunities and challenges in the assessment of drugs for atopic diseases
Authors: Bieber T. , Vieths S. , Broich K.
Published: October 2016

Atopic conditions (atopic dermatitis, rhinitis, and asthma) belong to the most common noncommunicable diseases and are driven by chronic inflammatory reactions. They have a strong impact on the quality of life and represent a substantial and growing socio‐economic burden. Interestingly, there is an increasing interest in the development of new therapeutic options with a number of biologics and small molecules targeting potential key mechanisms in atopic conditions. However, besides the safety issue, most of the new active substances are still evaluated according to the traditional efficacy paradigm focusing on the success in treating exacerbations and flares. Instead, the future approaches in drug development and assessment should rather concentrate on the long‐term control of these diseases and consider their potential as disease‐modifying strategies in the era of precision medicine. To reach this goal, a number of unsolved issues have to be addressed and consensually accepted by the stakeholders in this field. Thus, a successful and rapid development of new treatments requests a paradigm shift and a new way of thinking in the mind of physicians, pharmaceutical industry, regulators, and HTAs. This seems mandatory in order to optimize drug development and to facilitate the accessibility of new therapies to the growing population of patients suffering from atopic conditions on a global level.
A randomised controlled trial comparing the effects of propofol with isoflurane in patients with diastolic dysfunction undergoing coronary artery bypass graft surgery
Authors: Ammar A. , Mahmoud K. , Elkersh A. , Kasemy Z.
Published: October 2016

There is a strong association between pre‐operative diastolic dysfunction and difficulty in weaning from cardiopulmonary bypass. We compared the effects of propofol and isoflurane on left ventricular diastolic function in patients with pre‐existing diastolic dysfunction undergoing coronary artery bypass grafting. We randomly allocated 60 patients to receive either propofol or isoflurane anaesthesia, and assessed left ventricular diastolic function using transoesophageal echocardiography. We measured early (E), late (A) diastolic velocities, E/A ratio, A‐wave duration and deceleration time using pulsed wave Doppler, and early (Em), late (Am) diastolic velocities of the mitral annulus, Em/Am ratio and isovolumetric relaxation time using tissue Doppler. We measured pulmonary venous flow velocity and recorded values for the peak systolic flow velocity (S), peak diastolic flow velocity (D), S/D ratio, peak reverse atrial flow velocity and duration of reverse atrial flow. All data were recorded immediately after tracheal intubation as a baseline, 5 min before sternotomy (T1), 5 min before aortic cannulation (T2) and 15 min after weaning from cardiopulmonary bypass (T3). Both propofol and isoflurane improved left ventricular diastolic function as evidenced by significant increases in E/A ratios, and significant decreases in deceleration time and isovolumetric relaxation time; the improvement was greater in the isoflurane group (between groups, p = 0.001 for both E/A ratio and deceleration time at T1 and T2 and p = 0.006 for isovolumetric relaxation time at both T1 and T2). Furthermore, Em/Am ratio, S, D and S/D ratios were significantly better in the isoflurane group. The administration of isoflurane during cardiac surgery improves diastolic function comparatively more than propofol.
Remifentanil tolerance and hyperalgesia: short‐term gain, long‐term pain?
Authors: Yu E. H. Y. , Tran D. H. D. , Lam S. W. , Irwin M. G.
Published: October 2016

The unique pharmacology of remifentanil makes it a popular intra‐operative analgesic. Short‐acting opioids like remifentanil have been associated with acute opioid tolerance and/or opioid‐induced hyperalgesia, two phenomena which have different mechanisms and are pharmacologically distinct. Clinical studies show heterogeneity of remifentanil infusion regimens, durations of infusion, maintenance of anaesthesia, cumulative dose of remifentanil and pain measures, which makes it difficult to draw conclusions about the incidence of acute tolerance or hyperalgesia. However, it appears that intra‐operative remifentanil infusion rates of above 0.25 μg.kg−1.min−1 are associated with higher postoperative opioid consumption, suggesting tolerance. Infusion rates greater than 0.2 μg.kg−1.min−1 are characterised by lower mechanical/pressure/cold/pain thresholds, which suggests hyperalgesia. The use of concurrent multimodal analgesia, especially N‐methyl‐D‐aspartate receptor antagonists, may be an effective preventive strategy. The clinical significance and long‐term consequences of these entities is still uncertain.
A radiologic and anatomic assessment of injectate spread following transmuscular quadratus lumborum block in cadavers
Authors: Adhikary S. D. , El‐Boghdadly K. , Nasralah Z. , Sarwani N. , Nixon A. M. , Chin K. J.
Published: October 2016

We performed bilateral transmuscular quadratus lumborum blocks in six cadavers using iodinated contrast and methylene blue. Computed tomography imaging was performed in four cadavers and anatomical dissection was completed in five. This demonstrated spread to the lumbar paravertebral space in 63% of specimens, laterally to the transversus abdominis muscle in 50% and caudally to the anterior superior iliac spine in 63% of specimens. There was no radiographic evidence of spread to the thoracic paravertebral space. Anatomical dissection revealed dye staining of the upper branches of the lumbar plexus and the psoas major muscle in 70% of specimens. Further clinical studies are required to confirm if the quadratus lumborum block might be a suitable alternative to lumbar plexus block.
Trefoil factor peptide 3 is positively correlated with the viscoelastic properties of the cervical mucus plug
Authors: Bastholm Sara K. , Samson Mie H. , Becher Naja , Hansen Lea K. , Stubbe Peter R. , Chronakis Ioannis S. , Nexo Ebba , Uldbjerg Niels
Published: October 2016

Introduction

The viscoelastic properties of the cervical mucus plug are considered essential for the occlusion of the cervical canal and thereby for protection against ascending infections during pregnancy. Factors controlling this property are virtually unknown. This study explores a possible role of trefoil factor peptides 1, 2 and 3 (TFF1–3); peptides believed to influence mucus viscosity.

Material and methods

The study is based on spontaneously shed cervical mucus plugs from 14 women in active labor. The viscoelastic properties; the elastic modulus (G') and the viscous modulus (G”) were determined by an oscillatory rheometer. The concentrations of TFF1–3 were measured by an in‐house enzyme‐linked immunosorbent assay. Associations were analyzed by random‐effects generalized least‐squares regression analyses.

Results

Median (range) concentrations of TFF1, TFF2 and TFF3 were 3.1 (1.2–8.6), 1.1 (<0.006–3.7) and 1000 (170–5300) nmol/g cervical mucus plug, respectively. The TFF3 concentration was associated with G' (regression coefficient 11.7 Pa/Log nm; 95% CI 3.0–20.4, p = 0.009) and G” (regression coefficient 3.2 Pa/Log nm; 95% CI 1.5–5.0, p < 0.001).

Conclusion

We suggest that TFF3 plays a role in the viscoelastic properties of the cervical mucus plug.
Physician‐assisted dying for children is conceivable for most Dutch paediatricians, irrespective of the patient's age or competence to decide
Authors: Bolt Eva Elizabeth , Flens Eva Quirien , Pasman H. Roeline Willemijn , Willems Dick , Onwuteaka‐Philipsen Bregje Dorien
Published: October 2016

Aim

Paediatricians caring for severely ill children may receive requests for physician‐assisted dying (PAD). Dutch euthanasia law only applies to patients over 12 who make well‐considered requests. These limitations have been widely debated, but little is known about paediatricians' positions on PAD. We explored the situations in which paediatricians found PAD conceivable and described the roles of the patient and parents, the patient's age and their life expectancy.

Methods

We sent a questionnaire to a national sample of 276 Dutch paediatricians and carried out semi‐structured interviews with eight paediatricians.

Results

The response rate was 62%. Most paediatricians said performing PAD on request was conceivable (81%), conceivability was independent of the patient's age and whether the patient or parent(s) requested it. The paediatricians interviewed felt a duty to relieve suffering, irrespective of the patient's age or competency to decide. When this was not possible through palliative care, PAD was seen as an option for all patients who were suffering unbearably, although some paediatricians saw parental agreement and reduced life expectancy as prerequisites.

Conclusion

Most Dutch paediatricians felt PAD was conceivable, even under the age of 12 if requested by the parents. They seemed driven by a sense of duty to relieve suffering.
Evaluation and subsequent optimizations of the quantitative AmpliSens Florocenosis/Bacterial vaginosis‐FRT multiplex real‐time PCR assay for diagnosis of bacterial vaginosis
Authors: Rumyantseva Tatiana , Shipitsyna Elena , Guschin Alexander , Unemo Magnus
Published: October 2016

Traditional microscopy‐based methods for diagnosis of bacterial vaginosis (BV) are underutilized in many settings, and molecular techniques may provide opportunities for rapid, objective, and accurate BV diagnosis. This study evaluated the quantitative AmpliSens Florocenosis/Bacterial vaginosis‐FRT multiplex real‐time PCR (Florocenosis–BV) assay. Vaginal samples from a previous study including unselected female subjects (n = 163) and using Amsel criteria and 454 pyrosequencing for BV diagnosis were examined with the Florocenosis–BV test and additionally tested for the presence and quantity of Gardnerella vaginalis clades 3 and 4. The Florocenosis–BV assay demonstrated 100% and 98% sensitivity compared with the Amsel criteria and 454 pyrosequencing, respectively, with 91% specificity. The modified Florocenosis–BV assay (detecting also G. vaginalis clades 3 and 4) resulted in 100% sensitivity vs the Amsel criteria and 454 pyrosequencing with specificity of 86% and 88%, respectively. Further optimizations of thresholds for the quantitative parameters used in the kit resulted in 99–100% accuracy vs Amsel criteria and 454 pyrosequencing for selected parameters. The Florocenosis–BV assay is an objective, accurate, sensitive, and specific method for BV diagnosis; however, the performance of the test can be further improved with some minor optimizations.
A Mental Imagery Intervention to Increase Future Self‐Continuity and Reduce Procrastination
Authors: Blouin‐Hudon Eve‐Marie C. , Pychyl Timothy A.
Published: October 2016

This research examined how mental imagery practice can increase future self‐continuity to reduce procrastination. A total of 193 undergraduate students were randomly assigned to a present‐focused meditation or to a future self‐focused mental imagery condition. Participants in both conditions were asked to listen to their respective audio recording twice per week for four consecutive weeks and to complete a pre‐intervention, half‐point, and post‐intervention questionnaire. At the four‐week mark, hierarchical regression analyses revealed that both future self‐continuity and empathic perspective taking were significantly higher for the mental imagery condition than the meditation condition. While vividness of future self moderated change in future self‐continuity, affective empathy for future self mediated the relation between vividness of future self and future self‐continuity. Lastly, only empathic perspective taking was a significant moderator of change in procrastination across time. The influence of empathy and future self‐continuity on procrastination is discussed.
Prevalence of probable posttraumatic stress disorder and determination of its relationship with everyday functioning in children and adolescents by using generalized estimating equations
Authors: Zhang Ye , Zhang Jun , Zhu Shenyue , Du Changhui , Zhang Wei
Published: October 2016

Introduction

We investigated the prevalence rates for probable PTSD and used generalized estimating equations to identify risk factors for probable PTSD in children and adolescents exposed to the Lushan earthquake.

Methods

A total of 1623 participants completed 3 assessments, including the Children's Revised Impact of Event Scale, at 2 weeks, 3, and 6 months after experiencing the Lushan earthquake. Additionally, demographic variables and variables related to everyday functioning were evaluated at 2 weeks after the earthquake via a self‐constructed questionnaire.

Results

The percentages of children and adolescents who changed from having no PTSD to probable PTSD and probable PTSD to no PTSD at each time point were approximately 8% and 20% of the sample, respectively. The percentage of participants without PTSD increased from 41.1% at the 2‐week to 3‐month time point to 54.3% at the 3‐month to 6‐month time point, and the percentage with persistent probable PTSD decreased from 29.6% to 16.4% at the 2 time points, respectively. Female gender, a sedentary lifestyle, and actively helping others were significant risk factors for probable PTSD, whereas initiating communications with others, actively playing with classmates and friends, and the ability to concentrate on academic studies after resuming class were factors that helped protect against probable PTSD.

Discussion

Resistance to PTSD and persistent PTSD symptoms were both common occurrences in child and adolescent survivors. Specific variables related to everyday functioning may be risk factors for probable PTSD. These findings have implications for agencies that provide mental health services after an earthquake.
Effects of different rearing systems on growth, small intestinal morphology and selected indices of fermentation status in broilers
Authors: Li Jianhui , Miao Zhiqiang , Tian Wenxia , Yang Yu , Wang Jundong , Yang Ying
Published: October 2016

A 3×2 factorial experiment was conducted to determine the effects of rearing system and stocking density on the growth performance, intestinal morphology and fermentation status of broilers. Broilers were kept on three rearing systems: floor litter rearing (FRS), plastic net rearing (NRS) and multilayer cage rearing system (CRS), each with two stocking densities (normal and high stocking densities). Results showed that on 7 to 28 days of age, body weight gain appeared as FRS > NRS > CRS. Whereas, CRS significantly enhanced the weight gain of broilers compared with the other systems subsequently. Broilers on FRS had higher counts of cecum Bifidobacteria and Lactobacilli at 28 days of age but had more Escherichia coli and less Bifidobacteria than CRS at 42 days of age. The FRS also decreased volatile fatty acid (VFA) concentration and jejunal villus height‐to‐crypt depth ratio at all ages. In conclusion, FRS appeared to benefit gut microorganisms during the early growing period along with high body weight gain of broilers, whereas this system might have a harmful effect on subsequent intestinal growth, as indicated by high E. coli, low Bifidobacteria count, low VFA concentration and villus height‐to‐crypt depth ratio along with low weight gain of broilers.
HAS‐BLED Predicts Warfarin Control in Australian Patients treated for Deep Vein Thrombosis
Authors: Mueller Kylie , Bernaitis Nijole , Badrick Tony , Anoopkumar‐Dukie Shailendra
Published: October 2016

The HAS‐BLED model is widely utilized to assess patients' bleed risk prior to anticoagulant therapy including warfarin. Some of the variables assessed in the model are also known to influence warfarin control, commonly measured by time in therapeutic range (TTR). The aim of the study was to determine whether the HAS‐BLED risk tool is a good predictor of bleed risk and warfarin control in deep vein thrombosis (DVT) patients. Retrospective data were collected for DVT warfarin care patients at Sullivan Nicolaides Pathology. Data included age, medical history and concurrent drug therapy to calculate HAS‐BLED scores. INR results were used to calculate TTR with the Rosendaal method and mean TTR used for analysis and comparison. The eligible 533 patients had a mean TTR of 78.3%. Categorization according to HAS‐BLED score resulted in 150 patients classified as low‐risk, 331 as moderate‐risk and 52 as high‐risk with a haemorrhagic incidence per patient of 0.08, 0.53 and 0.54, respectively. Patients in the low‐, moderate‐ and high‐risk HAS‐BLED categories had a mean TTR of 81%, 79% and 65%, respectively, with significant differences (p < 0.001) found in TTR between the low‐ and high‐risk and moderate‐ and high‐risk categories. In an Australian DVT population, the HAS‐BLED score accurately predicts decreasing warfarin control with increasing risk category, and patients with scores ≥3 achieve poor control as indicated by a TTR <70%. In addition to predicting bleed risk, the HAS‐BLED tool may also predict the potential benefit of warfarin treatment and hence influence choice of anticoagulant therapy.
Repression of MicroRNA‐372 by Arsenic Sulphide Inhibits Prostate Cancer Cell Proliferation and Migration through Regulation of large tumour suppressor kinase 2
Authors: Cao Hongwen , Feng Yigeng , Chen Lei
Published: October 2016

As the main component of realgar, arsenic sulphide (As4S4) contains antitumour activity by repressing cancer cell proliferation and migration in many tumours. However, the detailed mechanism of these processes is not clear yet. MicroRNAs (miRNAs) can function as tumour suppressor or oncogene based on their target mRNAs in different tumour tissues. Here, we found that As4S4 could repress the overexpression of microRNA‐372 (miR‐372) in two prostate cancer cell lines and its overexpression promoted cell proliferation and migration. Large tumour suppressor kinase 2 (LATS2) was confirmed as a direct target of miR‐372 using luciferase assays in these two prostate cancer cell lines. Down‐regulation of LATS2 could promote prostate cancer cell proliferation and migration just as overexpression of miR‐372 did and overexpression of LATS2 could reverse this effect of miR‐372. The antitumour activity of As4S4 and the oncogenic function of miR‐372 were further confirmed using a mouse xenograft model. Altogether, our data showed evidence that repressing the overexpression of miR‐372 by As4S4 could inhibit prostate cancer cell proliferation and migration by targeting LATS2. Therefore, miR‐372 may be a possible biomarker for the prediction of prostate cancer and As4S4 may have potential therapeutic function for prostate cancer.
How we manage patients with hereditary haemochromatosis
Authors: Rombout‐Sestrienkova Eva , van Kraaij Marian G. J. , Koek Ger H.
Published: October 2016

A number of disorders cause iron overload: some are of genetic origin, such as hereditary haemochromatosis, while others are acquired, for instance due to repeated transfusions. This article reviews the treatment options for hereditary haemochromatosis, with special attention to the use of erythrocytapheresis. In general, therapy is based on the removal of excess body iron, for which ferritin levels are used to monitor the effectiveness of treatment. For many decades phlebotomy has been widely accepted as the standard treatment. Recent publications suggest that erythrocytapheresis, as a more individualized treatment, can provide a good balance between effectiveness, tolerability and costs. Other treatments like oral chelators and proton pomp inhibitors, which are used in selected patients, create the possibility to further individualize treatment of hereditary haemochromatosis. In the future, hepcidin‐targeted therapy could provide a more fundamental approach to treatment.
Multicentre, randomised phaseIIIstudy of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia
Authors: Yang Renchi , Li Junmin , Jin Jie , Huang Meijuan , Yu Ziqiang , Xu Xiaojun , Zhang Xiaohui , Hou Ming
Published: October 2016

Eltrombopag, a thrombopoietin receptor agonist, raises platelet counts and reduces bleeding in patients with immune thrombocytopenia (ITP). In Chinese patients, eltrombopag was evaluated at an initial dose of 25 mg, vs. 50 mg for non‐Asians, because the plasma exposure of eltrombopag is higher in East Asians. A multicentre, double‐blind, randomised, placebo‐controlled, 8‐week, phaseIIIstudy enrolled 155 patients with chronic, previously treatedITP. Dosage could be adjusted (25–75 mg/day) to maintain platelet counts 50–250 × 109/l. The primary efficacy endpoint was the proportion of patients with a platelet count ≥50 × 109/l after Day 42. Pharmacokinetics and pharmacodynamics of eltrombopag were analysed in an open‐label extension. After Day 42, 57·7% of eltrombopag‐treated and 6·0% of placebo‐treated patients achieved platelet counts ≥50 × 109/l. Odds of achieving a platelet count ≥50 × 109/l were 26·08 times greater with eltrombopag than placebo (P < 0·001). Compared with placebo, time to response and duration of response were better with eltrombopag (P < 0·001) and the odds of any bleeding were reduced by 72% (P = 0·001). Tolerability, pharmacokinetics, and pharmacokinetics/pharmacodynamics were similar to previous findings in East Asian patients. In conclusion, in Chinese patients with chronicITP, eltrombopag 25 mg once daily, elevated platelet counts to a safe range and reduced bleeding.
Development of a stretch‐induced neurotrauma model for medium‐throughput screening in vitro: identification of rifampicin as a neuroprotectant
Authors: López‐García Isabel , Gerő Domokos , Szczesny Bartosz , Szoleczky Petra , Olah Gabor , Módis Katalin , Zhang Kangling , Gao Jungling , Wu Ping , Sowers Lawrence C , DeWitt Doug , Prough Donald S , Szabo Csaba
Published: October 2016

Background and Purpose

We hypothesized that an in vitro, stretch‐based model of neural injury may be useful to identify compounds that decrease the cellular damage in neurotrauma.

Experimental Approach

We screened three neural cell lines (B35, RN33B and SH‐SY5Y) subjected to two differentiation methods and selected all‐trans‐retinoic acid‐differentiated B35 rat neuroblastoma cells subjected to rapid stretch injury, coupled with a subthreshold concentration of H2O2, for the screen. The model induced marked alterations in gene expression and proteomic signature of the cells and culminated in delayed cell death (LDH release) and mitochondrial dysfunction [reduced 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) conversion]. Follow‐up studies utilized human stem cell‐derived neurons subjected to rapid stretch injury.

Key Results

From screening of a composite library of 3500 drugs, five drugs (when applied in a post‐treatment regimen relative to stretch injury) improved both LDH and MTT responses. The effects of rifampicin were investigated in further detail. Rifampicin reduced cell necrosis and apoptosis and improved cellular bioenergetics. In a second model (stretch injury in human stem cell‐derived neurons), rifampicin pretreatment attenuated LDH release, protected against the loss of neurite length and maintained neuron‐specific class III β‐tubulin immunoreactivity.

Conclusions and Implications

We conclude that the current model is suitable for medium‐throughput screening to identify compounds with neuroprotective potential. Rifampicin, when applied either in pre‐ or post‐treatment, improves the viability of neurons subjected to stretch injury and protects against neurite loss. Rifampicin may be a candidate for repurposing for the therapy of traumatic brain injury.

Linked Articles

This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
Urbanizing physical geography
Authors: Ashmore Peter , Dodson Belinda
Published: October 2016

The physical environment of cities and processes of urbanization have a long‐standing presence in the field of physical geography and can give physical geography a renewed relevance in urban sustainability and planning. Existing approaches in physical geography will be a valuable component of this work. New insights and understanding of urban environments may be gained by engaging with ideas of urban landscapes as socio‐natures; adopting critical, political, and reflexive modes of thought and practice; and thinking beyond the physical structures and spatial boundaries of the city to planetary urbanization. Thinking about urban environments in these ways also opens up possible changes in the scope of, and approaches to, physical geography as a whole.

Urbaniser la géographie physique

L'environnement physique des villes et les processus d'urbanisation sont des sujets bien établis dans le domaine de la géographie physique qui peuvent contribuer à assurer sa pertinence en regard du développement durable et de l'urbanisme. Les approches existantes en géographie physique constitueront un atout pour ce travail. De nouvelles connaissances sur les environnements urbains peuvent être obtenues en partant de l'idée que les paysages urbains sont une construction socio‐naturelle ; en adoptant une perspective critique, politique et réflexive des cadres de pensée et d'action ; et en posant un regard sur l'urbanisation planétaire au‐delà des structures physiques et des limites territoriales de la ville. Cette façon de concevoir les environnements urbains permet d'accroître la portée et de modifier les approches de la géographie physique dans son ensemble.
Domesticating dialysis: A feminist political economy analysis of informal renal care in rural British Columbia
Authors: Brassolotto Julia , Daly Tamara
Published: October 2016

Key Messages

The movement of dialysis care to homes has distinct and under‐explored implications in a rural Canadian context.

The negative effects of this policy shift are felt most deeply by socially and economically vulnerable care providers.

The domestication of dialysis reflects a broader trend towards a reduction of public health services and reliance upon individuals, rather than the state, to provide the conditions for good health.
Negative income taxes, inequality and poverty
Authors: Angyridis Constantine , Thompson Brennan Scott
Published: October 2016

We use a neoclassical growth model with heterogeneous agents to analyze the redistributive effects of a negative income tax system, which combines a flat rate tax with a fully refundable credit (“demogrant”). We show that changing the demogrant‐to‐output ratio causes significant changes in the distribution of income. Specifically, we find that increasing the demogrant‐to‐output ratio sharply reduces the level of inequality as well as both relative and absolute poverty (all measured in terms of post‐tax total income). However, these reductions in inequality and poverty come at the expense of a significant reduction in output.
Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild‐type KRAS colorectal cancer‐WJOG 6210G
Authors: Shitara Kohei , Yonesaka Kimio , Denda Tadamichi , Yamazaki Kentaro , Moriwaki Toshikazu , Tsuda Masahiro , Takano Toshimi , Okuda Hiroyuki , Nishina Tomohiro , Sakai Kazuko , Nishio Kazuto , Tokunaga Shoji , Yamanaka Takeharu , Boku Narikazu , Hyodo Ichinosuke , Muro Kei
Published: October 2016

This randomized phase II trial compared panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) with bevacizumab plus FOLFIRI as second‐line chemotherapy for wild‐type (WT) KRAS exon 2 metastatic colorectal cancer (mCRC) and to explore the values of oncogenes in circulating tumor DNA (ctDNA) and serum proteins as predictive biomarkers. Patients with WT KRAS exon 2 mCRC refractory to first‐line chemotherapy containing oxaliplatin and bevacizumab were randomly assigned to panitumumab plus FOLFIRI or bevacizumab plus FOLFIRI. Of 121 randomly assigned patients, 117 were eligible. Median overall survival (OS) for panitumumab plus FOLFIRI and bevacizumab plus FOLFIRI were 16.2 and 13.4 months [hazard ratio (HR), 1.16; 95% CI, 0.76–1.77], respectively. Progression‐free survival (PFS) was also similar (HR, 1.14; 95% CI, 0.78–1.66). KRAS, NRAS, and BRAF status using ctDNA was successfully examined in 109 patients, and mutations were identified in 19 patients (17.4%). Panitumumab plus FOLFIRI showed favorable survival compared with bevacizumab plus FOLFIRI in WT patients and unfavorable survival in those with mutations (P for interaction = 0.026 in OS and 0.054 in PFS). OS with bevacizumab plus FOLFIRI was better than panitumumab plus FOLFIRI in patients with high serum vascular endothelial growth factor‐A (VEGF‐A) levels and worse in those with low levels (P for interaction = 0.016). Second‐line FOLFIRI plus panitumumab and FOLFIRI plus bevacizumab showed a similar efficacy in patients with WT KRAS exon 2 mCRC. RAS and BRAF mutation in ctDNA could be a negative predictive marker for panitumumab.
Synthesis of honokiol analogues and evaluation of their modulating action on VEGF protein secretion and telomerase‐related gene expressions
Authors: Sánchez‐Peris María , Murga Juan , Falomir Eva , Carda Miguel , Marco Juan Alberto
Published: October 2016

A group of 36 biphenyl derivatives structurally related to honokiol were synthesized by means of Suzuki coupling reactions. Their cytotoxicities were evaluated and compared to that of honokiol. Some of the compounds were then evaluated for their ability to downregulate the secretion of the VEGF protein and the expression of the VEGF, hTERT, and c‐Myc genes; the two latter involved in the activation of telomerase in tumoral cells. Some of the synthetized derivatives showed promising pharmacological features as they exhibited IC50 values in low micromolar range, good therapeutic margins, and a multiple mode of action on tumor cells based on the inhibition of VEGF and, at the same time, of the expression of genes related to the activation of telomerase.
Lifecourse socioeconomic position indicators and tooth loss in Korean adults
Authors: Han Dong‐Hun , Khang Young‐Ho
Published: October 2016

Aim

The aim of this study was to assess the association between lifecourse socioeconomic position (SEP) indicators and tooth loss in a large representative sample of the Korean adult population.

Methods

Data from the Fourth and Fifth Korea National Health and Nutritional Examination Survey on 17,549 Korean adults aged 50 years or older were analyzed. The study design was cross‐sectional. Tooth loss was defined as either edentulism (0 teeth) or severe tooth loss (<20 teeth). Parental education, own education, and income were used as indicators of early childhood SEP, adolescent SEP, and adulthood SEP, respectively. The association between the lifecourse SEPs and tooth loss was estimated with three different lifecourse models: the independent impact model for three different lifecourse SEPs, the cumulative impact model using the sum of the three SEP scores, and the social mobility model using the pathway information of the three SEPs. The covariates were demographic factors and health behaviors. The prevalence ratios (PRs), slope index of inequality (SII), and relative index of inequality (RII) for tooth loss were estimated with log‐binomial regression analyses.

Results

In the independent impact model, significant associations of each SEP with edentulism (SII=3.61%, 4.76%, 2.17% and RII=1.67, 1.52, 1.41 for parental education, own education, and income, respectively) and severe tooth loss (SII=8.03%, 17.73%, 12.73% and RII=1.26, 1.72, 1.42 for parental education, own education, and income, respectively) were found after adjusting for all covariates. For the cumulative impact model, stepwise patterns of PRs according to the summed SEP scores were found. In addition, in the social mobility model, the PR of tooth loss was greatest in the persistently low SEP group over the life course (PR=2.10 for edentulism and 2.33 for severe tooth loss). The other mobile groups in lifecourse SEPs also presented higher PRs of tooth loss than the persistently high SEP group.

Conclusion

Parental education was independently associated with edentulism in later life, and own education showed the strongest associations with tooth loss. The cumulative and social mobility models for the social impacts of life course on oral health should be considered in oral epidemiological studies.