bluuebunny/crossref_metadata_2025 huggingface dataset:
Network based statistics reveals trophic and neuroprotective effect of early high dose erythropoetin on brain connectivity in very preterm infants
Authors: Jakab András , Rüegger Christoph , Bucher Hans Ulrich , Makki Malek , Hüppi Petra , Tuura Ruth , Hagmann Cornelia ,   the Swiss EPO Neuroprotection Trial Group
Published: January 2019

Periventricular white matter injury is common in very preterm infants and it is associated with long term neurodevelopmental impairments. While evidence supports the protective effects of erythropoetin (EPO) in preventing injury, we currently lack the complete understanding of how EPO affects the emergence and maturation of anatomical brain connectivity and function. In this case-control study, connectomic analysis based on diffusion MRI tractography was applied to evaluate the effect of early high-dose EPO in preterm infants. A whole brain, network-level analysis revealed a sub-network of anatomical brain connections in which connectivity strengths were significantly stronger in the EPO group. This distributed network comprised connections predominantly in the frontal and temporal lobe bilaterally, and the effect of EPO was focused on the peripheral and feeder connections. EPO resulted in a globally increased clustering coefficient and higher local efficiency, while higher strength, efficiency and increased clustering was found for regions in the temporal lobe, supramarginal gyrus, inferior frontal gyrus, in the caudate and cingulate gyri. The connectivity network most affected by the EPO treatment showed a steeper increase in FA with age compared to the placebo group. These results demonstrate a weak but widespread effect of EPO on the structural connectivity network and a possible trophic effect of EPO reflected by increasing network segregation, predominantly in local connections.
Tubulin as a sensitive target of nanosecond-scale intense electric field: quantitative insights from molecular dynamics simulations
Authors: Marracino Paolo , Havelka Daniel , Průša Jiří , Liberti Micaela , Tuszynski Jack A. , Ayoub Ahmed T. , Apollonio Francesca , Cifra Michal
Published: January 2019

Intense pulsed electric fields are known to act at the cell membrane level and are already being exploited in biomedical and biotechnological applications. However, it is not clear if intra-cellular components such as cytoskeletal proteins could be directly influenced by electric pulses within biomedically-attainable parameters. If so, a molecular mechanism of action could be uncovered for therapeutic applications of such electric fields. To help clarify this question, we first identified that a tubulin heterodimer is a natural biological target for intense electric fields due to its exceptional electric properties and crucial roles played in cell division. Using molecular dynamics simulations, we then demonstrated that an intense - yet experimentally attainable - electric field of nanosecond duration can affect the β-tubulin’s C-terminus conformations and also influence local electrostatic properties at the GTPase as well as the binding sites of major tubulin drugs site. Our results suggest that intense nanosecond electric pulses could be used for physical modulation of microtubule dynamics. Since a nanosecond pulsed electric field can penetrate the tissues and cellular membranes due to its broadband spectrum, our results are also potentially significant for the development of novel therapeutic protocols.

Author summary

α/β-tubulin heterodimers are the basic building blocks of microtubules, that form diverse cellular structures responsible for essential cell functions such as cell division and intracellular transport. The ability of tubulin protein to adopt distinct conformations contributes to control the architecture of microtubule networks, microtubule-associated proteins, and motor proteins; moreover, it regulates microtubule growth, shrinkage, and the transitions between these states. Previous recent molecular dynamics simulations demonstrated that the interaction of the tubulin protein macrodipole with external electric field modifies orientation and conformations of key loops involved in lateral contacts: as a result, the stability of microtubules can be modulated by such fields. In this study, we seek to exploit these findings by investigating the possibility of fine-tuning the dipolar properties of binding sites of major drugs, by means of the action of electric fields. This may open the way to control tubulin-drug interactions using electric fields, thus modulating and altering the biological functions relative to the molecular vectors of microtubule assembly or disassembly. The major finding of our study reveals that intense (> 20 MV/m) ultra-short (30 ns) electric fields induce changes in the major residues of selected binding sites in a field strength-dependent manner.
Maximum Parsimony Interpretation of Chromatin Capture Experiments
Authors: Homouz Dirar , Kudlicki Andrzej
Published: January 2019

We present a new approach to inferring global geometric state of chromatin from Hi-C data. Chromatin conformation capture techniques (3C, and its variants: 4C, 5C, Hi-C, etc.) probe the spatial structure of the genome by identifying physical contacts between genomic loci within the nuclear space. In whole-genome conformation capture (Hi-C) experiments, the signal can be interpreted as spatial proximity between genomic loci and physical distances can be estimated from the data. However, the results of these estimations suffer from internal geometric inconsistencies, notoriously violating the triangle inequality. Here we propose that the inconsistencies may be caused not by experimental artifacts but rather by a mixture of cells, each in one of several conformational states, contained in the sample. We have developed and implemented a graph-theoretic approach that identifies the properties of these subpopulations. We show that the geometrical conflicts in a standard yeast HiC dataset, can be explained by only a small number of homogeneous populations of cells (4 populations are sufficient to reconcile 95,000 most prominent impossible triangles, 8 populations can explain 375,000 top geometric conflicts). Finally, we analyze the functional annotations of genes differentially interacting between the populations, suggesting that each inferred subpopulation may be involved in a functionally different transcriptional program.

Author Summary

The global conformation of chromatin within a nucleus plays an important role in regulation of genes. The Hi-C technique can detect proximity between genomic loci, but attempts to use Hi-C data to infer the global conformation lead to hundreds of thousands of impossible geometries, violating the triangle inequality. To date, there was no explanation for this phenomenon. Here, we resolve these discrepancies by modeling the sample as a mixture of nuclei in several conformation states. We have developed a graph-theoretic approach to characterize the shape of chromatin in each of these states. In a real-life situation, as few as 4-5 discrete subpopulations can resolve all spatial inconsistencies in the data. Moreover, the results suggest that each subpopulation is associated with a functionally specific transcriptional program.
ClinGen Expert Clinical Validity Curation of 164 Hearing Loss Gene-Disease Pairs
Authors: DiStefano Marina T. , Hemphill Sarah E. , Oza Andrea M. , Siegert Rebecca K. , Grant Andrew R. , Hughes Madeline Y. , Cushman Brandon J. , Azaiez Hela , Booth Kevin T. , Chapin Alex , Duzkale Hatice , Matsunaga Tatsuo , Shen Jun , Zhang Wenying , Kenna Margaret , Schimmenti Lisa A. , Tekin Mustafa , Rehm Heidi L. , Tayoun Ahmad N. Abou , Amr Sami S. ,   on behalf of the ClinGen Hearing Loss Clinical Domain Working Group
Published: January 2019

Purpose

Proper interpretation of genomic variants is critical to successful medical decision making based on genetic testing results. A fundamental prerequisite to accurate variant interpretation is the clear understanding of the clinical validity of gene-disease relationships. The Clinical Genome Resource (ClinGen) has developed a semi-quantitative framework to assign clinical validity to gene-disease relationships.

Methods

The ClinGen Hearing Loss Gene Curation Expert Panel (HL GCEP) uses this framework to perform evidence-based curations of genes present on testing panels from 17 clinical laboratories in the Genetic Testing Registry. The HL GCEP curated and reviewed 142 genes and 164 gene-disease pairs, including 105 nonsyndromic and 59 syndromic forms of hearing loss.

Results

The final outcome included 82 Definitive (50%), 12 Strong (7%), 25 Moderate (15%), 32 Limited (20%), 10 Disputed (6%), and 3 Refuted (2%) classifications. The summary of each curation is date stamped with the HL GCEP approval, is live, and will be kept up-to-date on the ClinGen website (https://search.clinicalgenome.org/kb/gene-validity).

Conclusion

This gene curation approach serves to optimize the clinical sensitivity of genetic testing while reducing the rate of uncertain or ambiguous test results caused by the interrogation of genes with insufficient evidence of a disease link.
Emergent microscale gradients give rise to metabolic cross-feeding and antibiotic tolerance in clonal bacterial populations
Authors: Co Alma Dal , van Vliet Simon , Ackermann Martin
Published: January 2019

Bacteria often live in spatially structured groups such as biofilms. In these groups, cells can collectively generate gradients through the uptake and release of compounds. In turn, individual cells adapt their activities to the environment shaped by the whole group. Here we studied how these processes can generate phenotypic variation in clonal populations and how this variation contributes to the resilience of the population to antibiotics. We grew two-dimensional populations of Escherichia coli in microfluidic chambers where limiting amounts of glucose were supplied from one side. We found that the collective metabolic activity of cells created microscale gradients where nutrient concentration varied over a few cell lengths. As a result, growth rates and gene expression levels varied strongly between cells close in space. Furthermore, we found evidence for a metabolic cross-feeding interaction between glucose fermenting and acetate respiring subpopulations. Finally, we found that the populations were able to survive an antibiotic pulse that was lethal in well-mixed conditions, likely due to the presence of a slow growing subpopulation. Our work shows that emergent metabolic gradients can have important consequences for the functionality of bacterial populations as they create opportunities for metabolic interactions and increase the populations’ tolerance to environmental stressors.
The Piezo channel is used by migrating cells to sense compressive load
Authors: Srivastava Nishit , Traynor David , Kabla Alexandre J. , Kay Robert R.
Published: January 2019

Migrating cells face varied mechanical and physical barriers in physiological environments, but how they sense and respond to them remains to be fully understood. We used a custom-built ‘cell squasher’ to apply uniaxial pressure to Dictyostelium cells migrating under soft agarose. Within 10 seconds of application, loads of as little as 100 Pa cause cells to move using blebs instead of pseudopods. Cells lose volume and surface area under pressure and their actin dynamics are perturbed. Myosin-II is recruited to the cortex, potentially increasing contractility and so driving blebbing. The blebbing response depends on extra-cellular calcium, is accompanied by increased cytosolic calcium and largely abrogated in null mutants of the Piezo stretch-operated channel. We propose that migrating cells sense mechanical force through mechano-sensitive channels, leading to an influx of calcium and cortical recruitment of myosin, thus re-directing the motile apparatus to produce blebs rather than pseudopods.
Stool-derived eukaryotic RNA biomarkers for detection of high-risk adenomas
Authors: Barnell Erica , Kang Yiming , Barnell Andrew , Campbell Katie , Kruse Kimberly R. , Wurtzler Elizabeth M. , Griffith Malachi , Chaudhuri Aadel A. , Griffith Obi L.
Published: January 2019

Background and aims

Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. Mortality is largely attributable to low patient compliance with screening and a subsequent high frequency of late-stage diagnoses. Noninvasive methods, such as stool- or blood-based diagnostics could improve patient compliance, however, existing techniques cannot adequately detect high-risk adenomas (HRAs) and early-stage CRC.

Methods

Here we apply cancer profiling using amplicon sequencing of stool-derived eukaryotic RNA for 275 patients undergoing prospective CRC screening. A training set of 154 samples was used to build a random forest model that included 4 feature types (differentially expressed amplicons, total RNA expression, demographic information, and fecal immunochemical test results). An independent hold out test set of 121 patients was used to assess model performance.

Results

When applied to the 121-patient hold out test set, the model attained a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 for CRC and a ROC AUC of 0.87 for CRC and HRAs. In aggregate, the model achieved a 91 % sensitivity for CRC and a 73% sensitivity for HRAs at an 89% specificity for all other findings (medium-risk adenomas, low-risk adenomas, benign polyps, and no findings on a colonoscopy).

Conclusion

Collectively, these results indicate that in addition to early CRC detection, stool-derived biomarkers can accurately and noninvasively identify HRAs, which could be harnessed to prevent CRC development for asymptomatic, average-risk patients.
Covalent-assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4-tert-butylbenzoic acid with isoniazid and its derivatized forms
Authors: Madeley Lee G. , Levendis Demetrius C. , Lemmerer Andreas
Published: January 2019

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4-tert-butylbenzoic acid via a one-pot covalent and supramolecular synthesis, namely 4-tert-butylbenzoic acid–isoniazid, C6H7N3O·C11H14O2, 4-tert-butylbenzoic acid–N′-(propan-2-ylidene)isonicotinohydrazide, C9H11N3O·C11H14O2, 4-tert-butylbenzoic acid–N′-(butan-2-ylidene)isonicotinohydrazide, C10H13N3O·C11H14O2, 4-tert-butylbenzoic acid–N′-(diphenylmethylidene)isonicotinohydrazide, C19H15N3O·C11H14O2, and 4-tert-butylbenzoic acid–N′-(4-hydroxy-4-methylpentan-2-ylidene)isonicotinohydrazide, C12H17N3O2·C11H14O2. The co-former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan-2-one, butan-2-one, benzophenone and 3-hydroxy-3-methylbutan-2-one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems.
Dichlorido(2,2′-methylenedipyridine)zinc(II)
Authors: Siegfried Adam , McAbee Brett , Zotov Vladimir , McMillen Colin , Hanks Timothy
Published: January 2019

The title complex, [ZnCl2(C11H10N2)], crystallizes in the P21/c space group with di-2-pyridylmethane acting as a bidentate ligand coordinating the zinc atom in a distorted tetrahedral geometry. The asymmetric unit consists of a single molecule of the title complex. The title complex folds with an angle of 53.82 (5)° between the planes of the two pyridine rings. The crystal packing is stabilized by hydrogen bonds and π–π interactions involving both pyridine rings.
Justifying students’ performance
Authors: Ukut Idorenyin Idorenyin Thomas , Krairit Donyaprueth
Published: January 2019

Purpose

The purpose of this study is to compare students and instructors’ perspectives on students’ performance based on unified theory of acceptance and use of technology (UTAUT) framework. This study also aims to propose additional variables that might be used to extend the UTAUT model to make it more appropriate for the educational setting.

Design/methodology/approach

The study was carried out using a three-pronged methodology, namely, literature review, expert interviews and self-administered survey of 430 students and 55 information and communication technology (ICT) instructors from tertiary institutions in Akwa Ibom State, Nigeria. Validity analysis were conducted using IBM SPSS version 24 and two structural equation models were finally obtained using AMOS version 24.

Findings

This study finds UTAUT constructs including social influence, facilitating condition and voluntariness of use to have direct and significant impact on students’ performance from the students and the instructors’ perspective. The result of the instructors’ perspective shows that ICT use behaviour of students have direct and significant impact on students’ performance, but the students’ result shows an insignificant direct effect of use behaviour on students’ performance. From the students and the instructors’ perspective, gender, age and experience have statistically significantly direct impact on performance expectancy in this study. The result also shows that additional variables including ICT instructors’ characteristics, motivation and personal environment directly affect students’ performance from the students’ perspective, but the result of the instructors’ perspective shows that the influence of ICT instructors’ characteristics, motivation and personal environment does not directly and significantly affect students’ performance.

Research limitations/implications

This study was limited to tertiary institutions in Akwa Ibom State, Nigeria. Consequently, the findings of this study are limited to Akwa Ibom State, Nigeria, and may not be generalised to cover other countries.

Originality/value

This research shows that the students and instructors have different views on variables that impact on students’ performance. This study finds empirical evidence to support the direct impact of use behaviour on students’ performance from the instructors’ perspective, while the students disagree but indicated an empirical evidence to show that instructors’ characteristics, environment and motivation contribute a greater impact on students’ performance. From the students and the instructors’ perspective, gender, age and experience have statistically significantly direct impact on performance expectancy in this study. This adds to the findings in the original UTAUT that indicated that performance expectancy is moderated by gender and age.
Effect of effortful swallowing training on tongue strength and oropharyngeal swallowing function in stroke patients with dysphagia: a double‐blind, randomized controlled trial
Authors: Park Hee‐Su , Oh Dong‐Hwan , Yoon Taehyung , Park Ji‐Su
Published: January 2019

Background

Effortful swallowing training (EST) is a remedial method for the training of swallowing‐related muscles in the oropharyngeal phase. However, clinical evidence of its effectiveness is insufficient.

Aims

To investigate the effects of EST on tongue strength and swallowing function in patients with stroke.

Methods & Procedures

Stroke patients with dysphagia were randomly assigned to one of two groups: an experimental group (n = 12) and a control group (n = 12). The experimental group underwent EST, while the control group performed saliva swallowing. Training was conducted 5 days per week for 4 weeks. Both groups underwent conventional dysphagia treatment for 30 min/day, 5 days/week for 4 weeks.

Outcomes & Results

Tongue strength was assessed using the Iowa Oral Performance Instrument. The Videofluoroscopic Dysphagia Scale (VDS), based on a videofluoroscopic swallowing study, was used to analyze oropharyngeal swallowing function. The experimental group showed greater improvements in anterior and posterior tongue strength compared with the control group (p = 0.046 and 0.042, respectively), and greater improvement in the oral phases of the VDS (p = 0.017).

Conclusions & Implications

We recommend EST as a remedial strategy for improving tongue strength and oral swallowing function in patients with stroke.
Sovereignty Beyond the State: Exception and Informality in a Western European City
Authors: Picker Giovanni
Published: January 2019

Bridging debates on urban sovereignty and urban informality, this paper argues that relationships between sovereignty and informality may not reside exclusively in the way the sovereign state decides to allow or forbid informality, but also in the way sovereignty is distributed among a range of state and non‐state actors. Drawing upon fieldwork on the early‐2010s management of displaced Romanian Romani families in two emergency camps in the city of Montreuil (France), the paper shows how the NGO responsible for managing one camp acted as sovereign power, allowing a number of informal activities to thrive within its confines. By contrast, inside the other camp, managed by another NGO that resolutely implemented state directives, only formal activities took place. Building on Dean's (2010) concept of ‘disaggregated sovereignty’, the paper mobilizes this disjuncture as a case for critically examining how the ‘state of exception’ takes shape beyond the state's grip. A subtext running throughout is the parallel between the very first camps for civilians in nineteenth‐century colonized territories and these twenty‐first‐century camps for Roma in Europe—both elicited a state of exception partially predicated on camp dwellers’ perceived ethnic/racial homogeneity.
The experiences of teachers of children with intellectual and developmental disabilities in inclusive schools in Accra, Ghana
Authors: Okyere Christiana , Aldersey Heather Michelle , Lysaght Rosemary
Published: January 2019

Although inclusive education is the best form of education for all children including those with disabilities, children with intellectual and developmental disabilities (IDD) in developing contexts such as Ghana are often educated in segregated settings or institutionalised. An understanding of teachers’ experiences with children with IDD in inclusion can inform strategies for more effective inclusive systems for children with IDD. We analysed the interview data from 16 general and two special educators who teach children with IDD. Participants shared their positive and negative experiences of educating children with IDD in inclusive schools in Accra, Ghana. Participants also shared their suggestions of classroom practices and learning strategies that might further facilitate inclusion of children with IDD in Ghana in the future. Identifying and addressing factors accounting for participants’ negative experiences while supporting and encouraging positive experiences may create more conducive spaces for accommodation of diversity and improvement of outcomes for children with IDD.
A Comprehensive Review on Kiwifruit Allergy: Pathogenesis, Diagnosis, Management, and Potential Modification of Allergens Through Processing
Authors: Wang Jin , Vanga Sai Kranthi , McCusker Christine , Raghavan Vijaya
Published: January 2019

Kiwifruit is rich in bioactive components including dietary fibers, carbohydrates, natural sugars, vitamins, minerals, omega‐3 fatty acids, and antioxidants. These components are beneficial to boost the human immune system and prevent cancer and heart diseases. However, kiwifruit is emerging as one of the most common elicitors of food allergies worldwide. Kiwifruit allergy results from an abnormal immune response to kiwifruit proteins and occur after consuming this fruit. Symptoms range from the oral allergy syndrome (OAS) to the life‐threatening anaphylaxis. Thirteen different allergens have been identified in green kiwifruit and, among these allergens, Act d 1, Act d 2, Act d 8, Act d 11, and Act d 12 are defined as the “major allergens.” Act d 1 and Act d 2 are ripening‐related allergens and are found in abundance in fully ripe kiwifruit. Structures of several kiwifruit allergens may be altered under high temperatures or strong acidic conditions. This review discusses the pathogenesis, clinical features, and diagnosis of kiwifruit allergy and evaluates food processing methods including thermal, ultrasound, and chemical processing which may be used to reduce the allergenicity of kiwifruit. Management and medical treatments for kiwifruit allergy are also summarized.
Regional favoritism and tax avoidance: evidence from China
Authors: Chen Yunsen , Huang Jianqiao , Liu Hang , Wang Weimin
Published: January 2019

This paper investigates the effect of officials’ regional favoritism on corporate tax avoidance activity in China. We find that firms located in regions that were formerly administered by the current provincial governors have a higher level of tax avoidance than other firms in the province. Further evidence indicates that regional favoritism affects tax avoidance through two channels: regional politicians’ personal connections with the governor and firms’ political access to the governor. Overall, the findings support China's current official selection and promotion guidelines that restrict hometown favoritism. Our results further imply that favoritism can also extend to officials’ former administrative regions.
The Hepatitis C Awareness Through to Treatment (HepCATT) study: improving the cascade of care for hepatitis C virus‐infected people who inject drugs in England
Authors: Harrison Graham I. , Murray Karen , Gore Roxanne , Lee Penelope , Sreedharan Aravamuthan , Richardson Paul , Hughes Amanda J. , Wiselka Martin , Gelson Will , Unitt Esther , Ratcliff Karen , Orton Annette , Trinder Kerry , Simpson Charlotte , Ryder Stephen D. , Oelbaum Sandra , Foster Graham R. , Christian Archie , Smith Stuart , Thomson Brian J. , Reynolds Rosy , Harris Magdalena , Hickman Matthew , Irving William L.
Published: January 2019

Background and Aims

Previous studies have shown low rates of diagnosis and treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID). Our aims were to test the effect of a complex intervention [Hepatitis C Awareness Through to Treatment (HepCATT)] in drug and alcohol clinics—primarily, on engagement of HCV‐positive PWID with therapy and, secondarily, on testing for HCV, referral to hepatology services and start of HCV treatment.

Design and setting

A non‐randomized pilot study in three specialist addiction clinics in England comparing an intervention year (starting between September 2015 and February 2016) with a baseline year (2014), together with three control clinics.

Participants

Analysis included all attendees at the intervention and control specialist addiction clinics identified as PWID.

Intervention

The intervention comprised the placement of a half‐time facilitator in each clinic for 12 months with the brief to increase diagnosis of HCV infection within clients at those services and the engagement of diagnosed individuals with an appropriate care pathway. The facilitator undertook various activities, which could include training of key workers, direct interaction with clients, streamlining and support for hepatology appointments and introduction of dried blood‐spot testing.

Measurements

For each clinic and period, we obtained the total number of clients and, as relevant, their status as PWID, tested for HCV, known HCV‐positive, engaged with HCV therapy or treated.

Findings

Compared with baseline, there was strong evidence that engagement with HCV therapy in the intervention year increased (P < 0.001) more in the HepCATT centres than controls, up +31 percentage points [95% confidence interval (CI) = 19–43] versus −12 (CI = –31 to +6) and odds ratio (OR) = 9.99 (CI = 4.42–22.6) versus 0.35 (CI = 0.08–1.56). HepCATT centres also had greater increases in HCV testing (OR = 3.06 versus 0.78, P < 0.001), referral to hepatology (OR = 9.60 versus 0.56, P < 0.001) and treatment initiation (OR = 9.5 versus 0.74, P < 0.001).

Conclusions

Introducing a half‐time facilitator into drug and alcohol clinics in England increased engagement of HCV‐positive people who inject drugs with hepatitis C virus care pathways, with increased uptake also of testing, referral to hepatology and initiation of treatment.
Clinical efficacy of concurrent bevacizumab for malignant ascites in nonsquamous cell carcinoma of the lung
Authors: Hsu Jui‐Feng , Lee Yen‐Lung , Chang Hsu‐Liang , Wei Po‐Ju , Shen Yu‐Ting , Lin Chi‐Min , Li Ching‐Yi , Chong Inn‐Wen , Yang Chih‐Jen
Published: January 2019

Purpose

Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies.

Methods

We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti‐angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms “lung cancer,” “peritoneal carcinomatosis” and “malignant ascites” to find other studies reporting experience of such treatment.

Results

Three consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression‐free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies.

Conclusions

Aggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab‐based treatment may serve as one effective treatment strategy for non‐squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.
A Travesty of British Justice? Appealing against Internment during the Second World War
Authors: Henderson David
Published: January 2019

In late 1940, the Australian government established Aliens Tribunals and Advisory Committees to ensure that local internees could, if they desired, protest against their internment. Most historians argue that this system of appeals was fundamentally flawed. This general explanation has much to commend it. Even so, the widely‐condemned appeals system requires some contextualisation. This article examines the appeal against internment of one man, Henry Brose, but it also seeks to place the appeals system in the broader context of the Australian government's attempt to balance personal liberty and national security over the course of the Second World War. The purpose of such an approach is not to offer a revision so much as a re‐contextualisation of an appeals system that historians have correctly described as flawed. This article demonstrates that the initial appeals system was certainly undermined by a government motivated by concerns for national security rather than personal liberty. But it also argues that the ongoing attempts of the Australian government to improve and overhaul the appeals system, in the midst of prosecuting an extraordinarily complex global war, suggests a more nuanced story than the one — of hapless victims and travesties of British justice — that has traditionally been told.
Oral health of adolescents in the Colac‐Otway Shire
Authors: Mayze Lara , Pawlak Jacqui , Rogers Margaret , Smith Michael
Published: January 2019

Objective

Altruistically, the developmental stage of adolescence poses a unique time frame to instil positive oral health behaviours. Caries are commonly associated with lower socioeconomic populations and regional or rural regions and are often prevalent in adolescents. This research project assessed the patterns of oral health and oral health behaviours of adolescents and investigated any potentially changeable behaviours or ways in which health services might support improvement in their oral health.

Design, setting and participants

Adolescents aged 11–17 years were recruited from four secondary schools in the Colac‐Otway Shire (n = 143). Students were screened for dental decay and the condition of tooth surfaces was recorded. Completion of a dental anxiety screening survey and a World Health Organization oral health behaviours survey was undertaken.

Main outcome measure

Early carious lesions and advanced decay.

Results

Early carious lesions were found in 86 (60%) of students and more advanced decay in 39 (28%). Dental decay was associated with consuming sweets and soft drinks, irregular dental check‐ups and students whose mother's highest education level was primary school. Consuming fruit was protective against decay.

Conclusion

This study identified that adolescents were experiencing high percentage of decay and not regularly visiting the dentist for dental screening. Programs that take the oral health therapists to regional and rural areas and lower socioeconomic areas might be warranted to target secondary schools.
Atypical choroideremia presenting with early‐onset macular atrophy
Authors: Kontos Georgios , Kwan Jennifer , Xue Kanmin , Patrício Maria I. , Clouston Penny , Packham Emily , MacLaren Robert E. , Downes Susan M.
Published: January 2019

Choroideremia is an X‐linked recessive retinal degeneration predominantly affecting hemizygous males. It is caused by mutations in the CHM gene that encodes the Rab escort protein‐1. Characteristic features include early nyctalopia followed by progressive constriction of peripheral visual fields and sparing of the central vision until late in life with a distinct fundoscopic appearance. We present the case of a 17‐year‐old male with a c.282delT in exon 4 of CHM that has not previously been reported. Phenotypically this patient presented with an atypical choroideremia phenotype of early central macular degeneration in addition to the classic peripheral fundus characteristic findings.
Influence of myopic macular degeneration severity on treatment outcomes with intravitreal aflibercept in the MYRROR study
Authors: Cheung Chui Ming Gemmy , Ohno‐Matsui Kyoko , Wong Tien Yin , Li Tummy , Asmus Friedrich , Leal Sérgio ,   MYRROR Study Investigators
Published: January 2019

Purpose

To determine the influence of baseline myopic macular degeneration (MMD) severity on outcomes with intravitreal aflibercept (IVT‐AFL) in patients with myopic choroidal neovascularization (CNV).

Methods

MYRROR was a randomized, double‐masked study in patients with myopic CNV treated with IVT‐AFL/sham over 48 weeks. At baseline/week 48, images were retrospectively graded for MMD.

Results

At baseline, 115 eyes had a valid MMD grading result; at week 48, grading results were available for 99 eyes [IVT‐AFL (n = 78)/sham (n = 21)]. Severity of baseline MMD was distributed as follows: category 1: 19/115 (17%); category 2: 67/115 (58%); category 3: 22/115 (19%); category 4: 7/115 (6%). Higher MMD category was associated with older age (nominal p = 0.007) and longer axial length (nominal p = 0.025). At week 48, patients in the mild and severe groups had visual acuity gains of +13.5 and +12.4 letters, respectively. Baseline MMD severity did not significantly affect visual/anatomical outcomes or number of treatments. Visual Functioning Questionnaire‐25 scores improved more in mild (+5.6) versus severe (+0.4) MMD (nominal p = 0.03). There were no new safety events.

Conclusions

Visual acuity gains, morphological outcomes and dosing frequency were not affected by baseline MMD severity in patients treated with IVT‐AFL. A benefit with IVT‐AFL treatment was observed for all baseline MMD stages included in this study.
“What a Match!”: The Specific Role of Resources in the Relation Between Demands and Vigour in Elite Sport
Authors: Balk Yannick A. , De Jonge Jan , Oerlemans Wido G.M. , Geurts Sabine A.E.
Published: January 2019

The triple‐match principle, as outlined by the Demand‐Induced Strain Compensation (DISC) Model, states that resources are most effective when they match particular demands. The present study investigates the role of match in elite sport with regard to the relation between sport‐related demands, sport‐related resources, and vigour (i.e., physical strength, cognitive liveliness, and emotional energy). We hypothesised that moderating effects of resources on the relation between demands and vigour are most likely when there is a triple‐match between demands, resources and vigour, followed by double‐match and non‐match. A cross‐sectional survey study was conducted among 118 semi‐professional and professional athletes (70 females, 48 males, Mage= 24.7, SD = 6.5). Physical resources moderated (i.e., strengthened) the positive relation between physical demands and physical strength, whereas emotional resources moderated (i.e., buffered) the negative relation between emotional demands and emotional energy. Moderating effects of sport‐related resources on the relation between sport‐related demands and vigour occurred more often when there was a triple‐match compared to when there was less match or no match at all. These findings indicate that, also in the domain of elite sport, resources do not randomly moderate the relation between demands and well‐being. Implications and limitations of the study are discussed.
Obsidian provenance analyses at Göytepe, Azerbaijan: Implications for understanding Neolithic socioeconomies in the southern Caucasus
Authors: Nishiaki Y. , Maeda O. , Kannari T. , Nagai M. , Healey E. , Guliyev F. , Campbell S.
Published: January 2019

This study presents a provenance analysis of the Neolithic obsidian assemblages from the early to mid‐sixth millennium bc settlement at Göytepe, Azerbaijan. The study is unique in that (1) it involves a complete, non‐selected obsidian assemblage (901 artefacts) from one particular area of the site; (2) the material is derived from a well‐stratified sequence of 10 securely radiocarbon‐dated architectural levels; and (3) the use of an extraordinarily wide range of sources (more than 20) was identified by provenance analysis using energy‐dispersive X‐ray fluorescence. The results reveal a previously unknown diachronic change in obsidian use in the region, suggesting the occurrence of significant socioeconomic changes during the Late Neolithic of the southern Caucasus.
Review of principles governing dog health education in remote Aboriginal communities
Authors: Willis EM , Ross KE
Published: January 2019

Background

Conducting effective and culturally sensitive dog health education programs in Aboriginal communities requires an understanding of appropriate adult education and community development principles. Finding relevant material can be difficult, given that many of the available resources are in the ‘grey literature’.

Aims and objectives

To critically review publications addressing the principles governing dog health education in remote Aboriginal communities.

Methods

A critical review was performed by searching English language peer‐reviewed and grey literature databases for papers published between 2010 and 2018. Besides a small number of peer‐reviewed papers, there was an extensive list of reports, educational material, guidelines and posters and pamphlets that illustrated the principles. Only a small amount of this grey literature was selected for the review. Selection was based on the publication illustrating a specific principle of dog health education. The material was organised around educational themes highlighting the strengths and weaknesses of these publications.

Results

Findings suggested that although relevant literature is scattered, there are clear processes for conducting culturally appropriate and effective dog health programs in Australian Indigenous communities. Two major principles were identified: acknowledging the effect on education of the ambiguity around the status of dogs in Aboriginal communities, and embedding programs within a social determinant of health framework or community development approach. These two principles provide guidance on negotiating educational sessions, the preparation of culturally appropriate materials, teaching sessions and what learning styles to foster and the use of a health promotion approach.

Conclusions

Some contradictions exist within the literature, particularly around the use of images, and consistent with the first principle, a hesitancy to engage with Aboriginal people around the issue of dog health.
Pharmacometrics and systems pharmacology for metabolic bone diseases
Authors: Riggs Matthew M. , Cremers Serge
Published: January 2019

Mathematical modelling and simulation (M&S) of drug concentrations, pharmacologic effects and the (patho)physiologic systems within which they interact can be powerful tools for the preclinical, translational and clinical development of drugs. Indeed, the Prescription Drug User Fee Act (PDUFA VI), incorporated as part of the FDA Reauthorization Act of 2017 (FDARA), highlights the goal of advancing model‐informed drug development (MIDD). MIDD can benefit development across many drug classes, including for metabolic bone diseases such as osteoporosis, cancer‐related and numerous rare metabolic bone diseases; conditions characterized by significant morbidity and mortality. A drought looms in terms of the availability of new drugs to better treat these devastating diseases. This review provides an overview of several M&S approaches ranging from simple pharmacokinetic to integrated pharmacometric and systems pharmacology modelling. Examples are included to illustrate the use of these approaches during the development of several drugs for metabolic bone diseases such as bisphosphonates, denosumab, teriparatide and sclerostin inhibitors (romosozumab and blosozumab).
A Two-Stage Experimental Design for Dilution Assays
Authors: Ferguson Jake M. , Miura Tanya A. , Miller Craig R.
Published: January 2019

Dilution assays to determine solute concentration have found wide use in biomedical research. Many dilution assays return imprecise concentration estimates because they are only done to orders of magnitude. Previous statistical work has focused on how to design efficient experiments that can return more precise estimates, however this work has not considered the practical difficulties of implementing these designs in the laboratory. We developed a two-stage experiment with a first stage that obtains an order of magnitude estimate and a second stage that concentrates effort on the most informative dilution to increase estimator precision. We show using simulations and an empirical example that the best two-stage experimental designs yield estimates that are remarkably more accurate than standard methods with equivalent effort. This work demonstrates how to utilize previous advances in experimental design in a manner consistent with current laboratory practice. We expect that multi-stage designs will prove to be useful for obtaining precise estimates with minimal experimental effort.
Living with epilepsy in adolescence—A qualitative study of young people's experiences in Singapore: Peer socialization, autonomy, and self‐esteem
Authors: Chew Judith , Carpenter John , Haase Anne M.
Published: January 2019

Background

Systematic reviews of quantitative research on the effects of childhood epilepsy have established its association with higher levels of psychiatric diagnosis, externalizing and internalizing problems, lower health‐related quality of life, social competence, and poorer academic achievements, compared with their peers. However, much less is known about young people's experiences of living with epilepsy and its impact on their development from their own perspectives.

Methods

Semistructured interviews were conducted with 15 young people aged between 13 and 16 years. Participants were recruited as part of a larger mixed methods study examining individual and family influences on outcomes for young people with epilepsy. These young people attended an epilepsy clinic in KK Women's and Children's Hospital, Singapore. The framework approach to data management and analyses involved both inductive and deductive generation of themes.

Results

Findings from young people's interviews provided in‐depth descriptions of stressful circumstances encountered. Interconnectedness between severity of the impairment and its impact on key developmental tasks, such as independence, autonomy, and social development, were emphasized. Seizures and illness‐related demands disrupted their day‐to‐day functioning and challenged their abilities to meet these tasks. In addition to these impairment effects, young people's experiences of social exclusion were also affected by social and environmental factors, which act as systemic barriers to participation. In turn, this has an effect on their self‐esteem. Nevertheless, young people reported positive experiences, such as support from both family and friends, which served as protective factors against the stress of living with a chronic medical condition.

Conclusion

The demands of epilepsy affect various domains of young people's lives. In order to obtain a holistic understanding of young people's inclusion or exclusion to participation, it is necessary to consider impairment effects, barriers to doing, and barriers to being.
Governance, sentiment analysis, and initial public offering underpricing
Authors: González Maximiliano , Guzmán Alexander , Tellez‐Falla Diego F. , Trujillo María Andrea
Published: January 2019

Research Question/Issue

What is the relationship between governance, tone in language, and underpricing of initial public offerings (IPOs) in Latin America?

Research Findings/Insights

We find a positive (negative) and statistically significant relationship between board size (board independence) and IPO underpricing at the time firms go public. But more importantly, when interacting with corporate governance variables at the firm level, uncertainty in tone still shows statistical significance, which suggests that tone in communications matters for underpricing independently of governance provisions at the firm level.

Theoretical/Academic Implications

Bigger boards seem to lead to greater underpricing, whereas more independent boards mitigate it. This finding stresses the relevance of functional convergence in regions with weak institutions such as Latin America. Our results also suggest that tone matters for underpricing even in firms with good governance practices. We argue that tone in corporate communications is a strong signaling mechanism for market participants.

Practitioner/Policy Implications

Our results suggest that tone in firms' communications is relevant for market valuation. In the context of family firms in an underresearched context such as Latin America, we show that reputation effect is priced by the market valuation of the IPO.