bluuebunny/crossref_metadata_2025 huggingface dataset:
Lentivirus‐mediated RNA Interference Targeting LAPTM4B Inhibits Human Ovarian Cancer Cell Invasion In Vitro
Authors: Meng Fanling , Chen Xiuwei , Song Hongtao , Lou Ge , Fu Songbin
Published: August 2015

LAPTM4B (lysosome‐associated protein transmembrane 4 beta) play an important role in several human carcinomas. We examines the effects of RNA interference mediated downregulation of human lysosomal‐associated protein transmembrane 4 beta expression on the biological behavior of the human serous adenocarcinoma cell line NIH:OVCAR3. This study investigated the expression level of lysosomal‐associated protein transmembrane 4 beta in several ovarian cancer cell lines. RNA interference mediated by recombinant lentiviral vectors expressing an artificial lysosomal‐associated protein transmembrane 4 beta miRNA was used to induce long‐lasting downregulation of lysosomal‐associated protein transmembrane 4 beta gene expression in NIH:OVCAR3 cells. Lysosomal‐associated protein transmembrane 4 beta expression as well as the motility, migration potential, and proliferation of the tumor cells was measured by flow cytometry, real‐time polymerase chain reaction, Western blot analysis, transwell migration assays, wound healing assays, and cell counting kit‐8 assays. In addition, the cell cycle analysis utilized fluorescence‐activated cell sorting. Four recombinant plasmid expression vectors encoding premiRNAs against lysosomal‐associated protein transmembrane 4 beta (pcDNA‐LAPTM4B‐miR‐1, ‐2, ‐3, and‐4) were constructed and transfected into 293T cells, which overexpress lysosomal‐associated protein transmembrane 4 beta. The recombinant lentiviral vector for lysosomal‐associated protein transmembrane 4 beta RNA interference was packaged with pcDNA‐LAPTM4B‐miR‐3, which had the highest interfering efficiency, thereby successfully generating stable transfectants. Compared with the control cells, the LAPTM4B‐miRNA‐transfected NIH:OVCAR3 cells exhibited significant decreases in cell motility and invasion. Furthermore, LAPTM4B depletion resulted in a significant decrease in proliferating cell nuclear antigen, vascular endothelial growth factor, MMP2, MMP9, and CDK12 expression. We propose that lysosomal‐associated protein transmembrane 4 beta expression may be an oncogene‐inducing feature of invasive ovarian cancer cells and may be a potential therapeutic target for ovarian cancer treatment.
Validation and adaptation of rapid neurodevelopmental assessment instrument for infants in Guatemala
Authors: Thompson L. , Peñaloza R. A. , Stormfields K. , Kooistra R. , Valencia‐Moscoso G. , Muslima H. , Khan N. Z.
Published: August 2015

Background

Timely detection of neurodevelopmental impairments in children can prompt referral for critical services that may prevent permanent disability. However, screening of impairments is a significant challenge in low‐resource countries. We adapted and validated the rapid neurodevelopmental assessment (RNDA) instrument developed in Bangladesh to assess impairment in nine domains: primitive reflexes, gross and fine motor development, vision, hearing, speech, cognition, behaviour and seizures.

Methods

We conducted a cross‐sectional study of 77 infants (0–12 months) in rural Guatemala in July 2012 and July 2013. We assessed inter‐rater reliability and predictive validity between the 27‐item RNDA and the 325‐item Bayley Scales of Infant and Toddler Development, Third Edition (BSID‐III) and concurrent validity based on chronic malnutrition, a condition associated with neurodevelopmental impairments. For both RNDA and BSID‐III, standardized scores below 80 were defined as borderline impairment.

Results

Children came from rural households (92%), were born to indigenous women of Mayan descent (73%) and had moderate or severe growth stunting (43%). Inter‐rater reliability for eight RNDA domains was of moderate to high reliability (weighted κ coefficients, 0.49–0.99). Children screened positive for impairment in fine motor (17%) and gross motor (14%) domains using the RNDA. The RNDA had good concurrent ability; infants who were growth stunted had higher mean levels of impairment in gross motor, speech and cognition domains (all p < 0.001). The RNDA took 20–30 min to complete compared with 45–60 min for BSID‐III.

Conclusions

Wide‐scale implementation of a simple, valid and reliable screening tool like the RNDA by community health workers would facilitate early screening and referral of infants at‐risk for neurodevelopmental impairment.
Elevated IL‐5 and IL‐13 responses to egg proteins predate the introduction of egg in solid foods in infants with eczema
Authors: Metcalfe J. R. , D'Vaz N. , Makrides M. , Gold M. S. , Quinn P. , West C. E. , Loh R. , Prescott S. L. , Palmer D. J.
Published: August 2015

Background

Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen‐specific T‐cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure.

Objective

To investigate the early T‐cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE‐mediated egg allergy.

Methods

Egg‐specific T‐cell cytokine responses (IL‐5, IL‐13, IL‐10, IFNγ and TNFα) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive ‘early egg’ or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE‐mediated egg allergy was assessed by skin prick test and food challenge.

Results

In 4–month‐old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL‐13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL‐5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL‐13 responses (to OVA and LYS) and IL‐5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg‐allergic infants, and this did not appear to be modified by ‘early’ introduction of egg.

Conclusions & Clinical Relevance

Elevated egg‐specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.
Evaluation of adipocytokines and traditional cardiometabolic risk factors in young male cancer survivors: an age‐matched control study
Authors: Greenfield Diana M. , Blewitt Alice , Coleman Robert E. , Walsh Jennifer S. , Snowden John A. , Ross Richard J.M. , Han Thang S.
Published: August 2015

Background

Life expectancy of cancer survivors has doubled in the past four decades; however, death due to cardiovascular disease is more prevalent in survivors than the general population.

Objective, design and methods

We evaluated novel and traditional cardiometabolic risk factors in young male cancer survivors in a cross‐sectional study of male cancer survivors aged 25–45 years compared with age‐matched noncancer controls. Demographic and anthropometric data were recorded and biochemical and hormonal parameters assayed from fasting blood samples in 176 survivors and 213 controls (lipids were measured in all survivors and 97 controls).

Results

Compared with controls, survivors had significantly higher body mass index, adipocytokines, insulin resistance, total cholesterol and triglyceride levels and lower free androgen index (FAI). Handgrip strength, smoking, alcohol consumption, free oestrogen index, insulin‐like growth factor 1 and high‐density lipoprotein cholesterol levels did not differ between cancer survivors and controls. Risk factors were analysed simultaneously using stepwise multivariable logistic regression, and this showed that high leptin: adiponectin ratio (odds ratio = 2·63; 95% confidence interval: 1·34–5·15; P = 0·005), hypercholesterolaemia (odds ratio = 1·85; 95%CI: 1·08–3·17; P = 0·025) and low FAI (odds ratio = 2·01; 95% confidence interval: 1·07–3·79; P = 0·030) were independently more common in survivors. The odds ratio in survivors for having at least two of these three risk factors rose to 6·58 (95% confidence interval: 3·30–13·12; P < 0·001). Among survivors, risk factors were not different between cancer therapies but worse in survivors who had radiotherapy involving the testes (hyperleptinaemia and insulin resistance) or age at diagnosis above group median (hypertriglyceridaemia and hypercholesterolaemia).

Conclusions

A high leptin: adiponectin ratio, hypercholesterolaemia and low FAI are observed in young male cancer survivors, especially those who received radiotherapy involving the testes or were diagnosed at a later age. In view of their youth and known increased risk of cardiovascular death, treatment strategies are required to address this cardiovascular risk.
Polymicrogyria: the common endpoint of many different aetiological processes
Authors: Ten Donkelaar Hans J
Published: August 2015

This commentary is on the original article by Jansen et al. on pages 39–48 of this issue.
IMMIGRANT NETWORKS AND THE TAKE‐UP OF DISABILITY PROGRAMS: EVIDENCE FROM THE UNITED STATES
Authors: Furtado Delia , Theodoropoulos Nikolaos
Published: August 2015

We examine the role of ethnic networks in disability program take‐up among working‐age immigrants in the United States. Controlling for country of origin and area of residence fixed effects, immigrants residing amid a large number of co‐ethnics are more likely to receive disability payments when their ethnic groups have higher take‐up rates. Differences in satisfying the work history or income and asset requirements of the disability programs explain part of this relationship, but social norms also play an important role. Information sharing appears influential for Supplemental Security Income take‐up but not for Social Security Disability Income. (JEL J61, H55, I18)
Integrating macroecological metrics and community taxonomic structure
Authors: Harte John , Rominger Andrew , Zhang Wenyu
Published: August 2015

We extend macroecological theory based on the maximum entropy principle from species level to higher taxonomic categories, thereby predicting distributions of species richness across genera or families and the dependence of abundance and metabolic rate distributions on taxonomic tree structure. Predictions agree with qualitative trends reported in studies on hyper‐dominance in tropical tree species, mammalian body size distributions and patterns of rarity in worldwide plant communities. Predicted distributions of species richness over genera or families for birds, arthropods, plants and microorganisms are in excellent agreement with data. Data from an intertidal invertebrate community, but not from a dispersal‐limited forest, are in excellent agreement with a predicted new relationship between body size and abundance. Successful predictions of the original species level theory are unmodified in the extended theory. By integrating macroecology and taxonomic tree structure, maximum entropy may point the way towards a unified framework for understanding phylogenetic community structure.
Habitat type and dispersal ability influence spatial structuring of larval Odonata and Trichoptera assemblages
Authors: Curry Colin J. , Baird Donald J.
Published: August 2015

Freshwater invertebrate assemblages are believed to be structured by both local and larger scale processes (i.e. dispersal). In rivers, the extent to which dispersal processes influence local assemblage composition may depend on both the taxon and habitat in question. Poor dispersers should display greater spatial structuring than strong dispersers. Likewise, assemblages in poorly connected habitats should experience greater dispersal limitation, and therefore greater spatial structuring.

We sought to test these hypotheses using two contrasting orders of aquatic insect, Odonata and Trichoptera. Odonata are believed to have greater dispersal capacity than Trichoptera. In river ecosystems, these orders inhabit both main channel habitats and more poorly connected riverine wetlands. Multi‐habitat surveys of larval Trichoptera and Odonata assemblages were conducted at 34 sites in three 5th‐order New Brunswick rivers. The degree of spatial and environmental structuring in assemblages was assessed using redundancy analysis‐based variance partitioning. We also assessed the performance of different model‐based spatial predictors (asymmetric eigenvector maps, AEMs and principal coordinates of neighbourhood matrices, PCNMs).

For main channel areas, variance explained purely by environmental variables was greater for Odonata, while the purely spatial component of variance was greater for Trichoptera, regardless of the class of spatial descriptor. In riverine wetlands, both the purely environmental and purely spatial components of variance explained were similar or were greater for Trichoptera than for Odonata.

The component of variance explained by spatial variables was greater in riverine wetlands than main channel areas for both Odonata and Trichoptera for most spatial descriptors, suggesting that taxa inhabiting riverine wetlands may experience greater dispersal limitation. However, the magnitude of this difference was relatively small in most cases. Eigenvector‐based spatial descriptors (PCNMs, AEMs, netPCNMs) explained more variance than traditional spatial descriptors. For Trichoptera, network‐based predictors (AEMs, netPCNMs) explained more variance than PCNMs in main channel areas.

Our results suggest that dispersal ability and habitat type can influence the degree of spatial structuring in aquatic insect assemblages. However, these patterns must be investigated across a wider range of insect groups and at larger spatial scales. Our results also suggest that biomonitoring programs should consider assemblage spatial structure in building reference condition models and that aquatic conservation planners must consider the type and spatial arrangement of habitats in reserve design. Eigenvector‐based spatial descriptors hold promise for interpreting biodiversity patterns in freshwater invertebrates, but more work is required to relate patterns to actual dispersal behaviour.
Effects of the presence of a predatory fish and the phenotype of its prey (a shredding shrimp) on leaf litter decomposition
Authors: Ocasio‐Torres María E. , Crowl Todd A. , Sabat Alberto M.
Published: August 2015

The role of inducible defences in trophic cascades is poorly understood. The shrimp shredder Xiphocaris elongata has a short rostrum in the absence of predatory fishes and a long rostrum in their presence. The long rostrum in X. elongata is a morphological defence that is inducible by the predatory fish Agonostomus monticola (mountain mullet).

Our objective was to measure the effect of fish presence and absence and shrimp phenotype (long rostrum versus short rostrum) on the foraging behaviour of X. elongata and on the decomposition of leaves of the riparian tree Cecropia schreberiana, including their potential for direct or trait‐mediated top‐down trophic cascades effects.

Experiments were carried out in wading pools in which leaf discs of C. schreberiana were exposed for 24 days to processing by either microbes or short‐rostrum or long‐rostrum X. elongata in either the presence or absence of the predatory fish A. monticola. Shrimp foraging activities, shrimp survival and leaf decomposition were quantified.

Shrimp density was not affected by fish presence. However, fish presence decreased foraging activity of long‐rostrum X. elongata presumably by increasing their use of refugia throughout the experiments. The foraging of short‐rostrum shrimps did not respond to fish presence.

The fraction of leaf mass remaining was significantly higher when shrimps were in the presence of fish than when fish were absent, particularly when short‐rostrum shrimps were shredding leaves. Shrimps decreased the fraction of mass remaining of C. schreberiana more than the effect of microbial colonisation alone.

These results demonstrate that the presence of the predatory fish A. monticola can create trait‐mediated top‐down trophic cascades in the presence of short‐rostrum X. elongata. This study provides evidence that predators have different effects on prey with morphological inducible defences than prey without defences and that these interactions may have critical consequences for other trophic levels.
How good are Bayesian belief networks for environmental management? A test with data from an agricultural river catchment
Authors: Death Russell G. , Death Fiona , Stubbington Rachel , Joy Michael K. , van den Belt Marjan
Published: August 2015

The ecological health of rivers worldwide continues to decline despite increasing effort and investment in river science and management. Bayesian belief networks (BBNs) are increasingly being used as a mechanism for decision‐making in river management because they provide a simple visual framework to explore different management scenarios for the multiple stressors that impact rivers. However, most applications of BBN modelling to resource management use expert knowledge and/or limited real data, and fail to accurately assess the ability of the model to make predictions.

We developed a BBN to model ecological condition in a New Zealand river using field/GIS data (from multiple rivers), rather than expert opinion, and assessed its predictive ability on an independent data set. The developed BBN performed moderately better than a number of other modelling techniques (e.g. artificial neural networks, classification trees, random forest, logistic regression), although model construction was more time consuming. Thus, the predictive ability of BBNs is (in this case at least) on a par with other modelling methods but the approach is distinctly better for its ability to visually present the data linkages, issues and potential outcomes of management options in real time.

The BBN suggested management of habitat quality, such as riparian planting, along with the current management focus on limiting nutrient leaching from agricultural land may be most effective in improving ecological condition.

BBNs can be a powerful and accurate method of effectively portraying the multiple interacting drivers of environmental condition in an easily understood manner. However, most BBN applications fail to appropriately test the model fit prior to use. We believe this lack of testing may seriously undermine their long‐term effectiveness in resource management and recommend that BBNs should be used in conjunction with some measure of uncertainty about model predictions. We have demonstrated this for a BBN of ecological condition in a New Zealand river, shown that model fit is better than that for other modelling techniques, and that improving habitat would be equally effective to reducing nutrients to improve ecological condition.
Early symptoms of Alzheimer's disease in Japan and Taiwan
Authors: Yang Yuan‐Han , Hsu Chia‐Ling , Chou Mei‐Chuan , Kasai Mari , Meguro Kenichi , Liu Ching‐Kuan
Published: August 2015

Aim

The effects of Alzheimer's disease (AD) are making a major impact on the socioeconomic status of older adults in society. The recognition of early symptoms and clinical presentation are crucial issues to foster early diagnosis and treatment in order to have better therapeutic outcomes.

Methods

We recruited clinically diagnosed AD patients at the very mild stage in the Clinical Dementia Rating scale 0.5 and mild stage Clinical Dementia Rating scale 1.0 in Taiwan and Japan. Psychometrics including the Ascertain Dementia 8 (AD8) questionnaire were administered to collect and compare the differences of the clinical presentation of the participants from the two countries.

Results

A total of 1189 participants, 641 from Taiwan and 548 from Japan, were recruited in the present study. In the very mild dementia group with Clinical Dementia Rating scale 0.5, apart from AD8‐2: reduced interest in hobbies/activities (P = 0.056) and AD8‐4: trouble learning how to use a tool, appliance or gadget (P = 0.224), other AD8 subitems were significantly different between the two countries. Japanese participants had a higher reported frequency of AD8‐5: forgetting the correct month or year (82.7%) than that (57.9%) in Taiwanese (P < 0.001). Taiwanese participants had a higher reported frequency in AD8‐1: problems with judgment (20.3%), AD8‐3: repeats questions, stories or statements (67.5%), AD8‐6: difficulty handling complicated financial affairs (32.5%); AD8‐7: difficulty remembering appointments (53.8%); and AD8‐8: consistent problems with thinking and/or memory (89.3%) than those in Japanese participants.

Conclusion

Early symptoms of AD in both countries are different. The frequently reported early symptoms are important for primary physicians and the general population so that they can recognize the disease in the early stage so as to have a better therapeutic outcome. Such efforts would increase the awareness of dementia in the general population. Geriatr Gerontol Int 2016; 16: 797–803.
Factors predicting perioperative delirium and acute exacerbation of behavioral and psychological symptoms of dementia based on admission data in elderly patients with proximal femoral fracture: A retrospective study
Authors: Tanaka Tomohiro
Published: August 2015

Aim

To examine factors predicting the onset of perioperative delirium and acute exacerbation of behavioral and psychological symptoms of dementia (BPSD), based on patient background, operative background and laboratory data obtained on admission, in elderly patients with proximal femoral fracture.

Methods

The participants were 152 patients (aged >70 years) who underwent surgery between 1 November 2012 and 31 March 2014. The participants were classified into group B (with onset of perioperative delirium or acute exacerbation of BPSD, n = 52), or group N, (without onset, n = 100), and risk factors were retrospectively examined. Onset was judged based on the presence or absence of common items; that is, “hallucination and delusion,” “disturbing speech,” “excitatory behavior” and “altered sleep‐wake cycle.” The participants were observed for 1 week after admission.

Results

The incidence of perioperative delirium or acute exacerbation of BPSD was 34.2% in total. In univariate analysis, the incidence was significantly higher (P < 0.005) in group B for the age, history of dementia and serum albumin level items. In multivariate analysis, history of dementia, serum albumin level and peripheral lymphocyte count (odds ratio 3.55, 0.17, 1.00, respectively) were identified as independent predictive factors. In the subanalysis, the incidence was 91.3% in the group with a history of dementia, serum albumin level <3.7 g/dL and peripheral lymphocyte count < 1200/μL.

Conclusions

History of dementia, a low serum albumin level and low peripheral lymphocyte count were found to be useful factors for predicting the onset of perioperative delirium and acute exacerbation of BPSD. Geriatr Gerontol Int 2016; 16: 821–828.
Mortality in Brazilian community‐dwelling older adults: 7 years of follow up in primary care
Authors: Ferreira Talita Cristina Barbosa Rezende , Coimbra Arlete Maria Valente , Falsarella Glaucia Regina , Costallat Lilian Tereza Lavras , Coimbra Ibsen Bellini
Published: August 2015

Aim

To describe the main causes and factors associated with mortality in community‐dwelling older adults in a county where the public health system covers most of the population.

Methods

We analyzed data from an existing cross‐sectional study of 2209 participants (age ≥60 years) in a city in southeast Brazil where 92% of the population is served by a public system of primary care. Over a period of 7 years, 386 participants died and were included in the sample. We assessed the impacts that dependence on others for basic activities of daily living and instrumental activities of daily living, Geriatric Depression Scale scores, and health history have on mortality.

Results

The participants' mean age was 75.2 years (SD 8.2); 51.7% of the participants were women, and 51.3% had depressive symptoms. The main causes of death were circulatory diseases (40.3%), cancer (19.8%) and respiratory diseases (13.5%). Multivariate analysis showed that, taken together, the use of more than four medications per day, smoking, lower income, older age and dependence on others for a greater number of instrumental activities of daily living predicted death in this population.

Conclusions

Understanding the factors that are associated with mortality can facilitate understanding, and aid in developing policies regarding primary care for the elderly. Geriatr Gerontol Int 2016; 16: 804–809.
Chronic obstructive pulmonary disease in patients with end‐stage kidney disease on hemodialysis
Authors: Plesner Louis L. , Warming Peder E. , Nielsen Ture L. , Dalsgaard Morten , Schou Morten , Høst Ulla , Rydahl Casper , Brandi Lisbet , Køber Lars , Vestbo Jørgen , Iversen Kasper
Published: August 2015

The objectives of this study were to assess the prevalence of chronic obstructive pulmonary disease (COPD) in hemodialysis patients with spirometry and to examine the effects of fluid removal by hemodialysis on lung volumes. Patients ≥18 years at two Danish hemodialysis centers were included. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio were measured with spirometry before and after hemodialysis. The diagnosis of COPD was based on both the GOLD criteria and the lower limit of normal criteria. There were 372 patients in treatment at the two centers, 255 patients (69%) completed spirometry before dialysis and 242 of these (65%) repeated the test after. In the initial test, 117 subjects (46%) had airflow limitation indicative of COPD with GOLD criteria and 103 subjects (40.4%) with lower limit of normal criteria; COPD was previously diagnosed in 24 patients (9%). Mean FVC and FEV1 decreased mildly after dialysis (FVC: 2.84 to 2.79 L, P < 0.01. FEV1: 1.97 to 1.93 L, P < 0.01) Hemodialysis did not affect the FEV1/FVC ratio or number of subjects with airflow limitation indicative of COPD (113 vs. 120, P = 0.324; n = 242). COPD is a frequent and underdiagnosed comorbidity in patients on chronic hemodialysis. Spirometry should be considered in all patients on dialysis in order to address dyspnea adequately. Hemodialysis induced a small fall in mean FEV1 and FVC, which was more pronounced in patients with little or no fluid removal, but the FEV1/FVC ratio and the number of subjects with airflow limitation indicative of COPD were not affected by dialysis.
Calculation of the clearance requirements for the development of a hemodialysis‐based wearable artificial kidney
Authors: Kim Dong Ki , Lee Jung Chan , Lee Hajeong , Joo Kwon Wook , Oh Kook‐Hwan , Kim Yon Su , Yoon Hyung‐Jin , Kim Hee Chan
Published: August 2015

Wearable artificial kidney (WAK) has been considered an alternative to standard hemodialysis (HD) for many years. Although various novel WAK systems have been recently developed for use in clinical applications, the target performance or standard dose of dialysis has not yet been determined. To calculate the appropriate clearance for a HD‐based WAK system for the treatment of patients with end‐stage renal disease with various dialysis conditions, a classic variable–volume two‐compartment kinetic model was used to simulate an anuric patient with variable target time‐averaged creatinine concentration (TAC), daily water intake volume, daily dialysis pause time, and patient body weight. A 70‐kg anuric patient with a HD‐based WAK system operating for 24 h required dialysis clearances of creatinine of at least 100, 50, and 25 mL/min to achieve TACs of 1.0, 2.0, and 4.0 mg/dL, respectively. The daily water intake volume did not affect the clearance required for dialysis under various conditions. As the pause time per day for the dialysis increased, higher dialysis clearances were required to maintain the target TAC. The present study provided theoretical dialysis doses for an HD‐based WAK system to achieve various target TACs through relevant mathematical kinetic modeling. The theoretical results may contribute to the determination of the technical specifications required for the development of a WAK system.
Mediator Variables in Headache Research: Methodological Critique and Exemplar Using Self‐Efficacy as a Mediator of the Relationship Between Headache Severity and Disability
Authors: Peck Kelly R. , Smitherman Todd A.
Published: August 2015

Background

Despite advances in headache medicine, there remains little research on process‐related variables that mediate relations between headache and outcomes, as well as limited dissemination of optimal statistical methodology for conducting mediation analyses. The present paper thus aims to promote and demonstrate a contemporary approach to mediation analysis as applied to headache.

Methods

An overview of a contemporary path‐analytic approach to mediation analysis is presented, with an empirical exemplar for illustrative purposes. In the exemplar, headache management self‐efficacy (HMSE) was proposed as a mediator between headache severity and disability. The sample included 907 young adults (M age = 19.03 [SD = 2.26]; 70.8% female) with primary headache. Direct and indirect effects of headache severity on headache disability through HMSE were assessed using the espoused methods.

Results

Pain severity was positively associated with headache disability (β = 2.91, 95% confidence interval [CI; 2.62, 3.19]) and negatively associated with HMSE (β = −3.50, 95% CI [−4.24, −2.76]); HMSE was negatively associated with headache disability (β = 0.07, 95% CI [−0.09, −0.04]). A positive indirect effect of pain severity on disability through HMSE was identified (point estimate = 0.24, 95% CI [0.14, 0.34]); thus, self‐efficacy mediated the association between pain severity and disability. The proposed mediation model accounted for 38% of total variance in disability (P < .001).

Conclusions

There is a need for theory‐driven and statistically rigorous mediation analyses within the headache literature. In one exemplar application, self‐efficacy partially accounted for the disability resulting from headache. We advocate for increased attention to intervening variables in headache via dissemination of contemporary mediation analyses.
Selective fractionation of cholesterol from whole milk powder: optimisation of supercritical process conditions
Authors: Chitra Jayakumar , Deb Shyamali , Mishra Hari N.
Published: August 2015

Supercritical fluid extraction (SCFE) of cholesterol from whole milk powder (WMP) was investigated in this study. The combined effects of temperature (40–80 °C) and pressure (150–250 bar) on the efficacy of cholesterol extraction (mg 100 g−1), modifications in the fat content (FC) (%) and solubility index (SI) (%) of WMP were studied and optimised by the application of response surface methodology (RSM). Variations in the free fatty acids (FFAs) (mg oleic acid per 100 g of milk fat) and lightness value (L*) were also investigated after SCFE process. About 55.8% reduction in cholesterol was achieved at the optimised condition of 68 °C, 207 bar with 40 min static time and 2 h dynamic time at flow rate of 6 L min−1. Extraction at the optimised conditions maximised the yield of cholesterol while retaining the FC, SI, FFA and L* at moderate limits of 23.7%, 85.1%, 7.7 mg per 100 g milk fat and 95.4, respectively.
Atypical haemolytic uraemic syndrome treated with the complement inhibitor eculizumab: the experience of the Australian compassionate access cohort
Authors: Mallett A. , Hughes P. , Szer J. , Tuckfield A. , Van Eps C. , Cambell S. B. , Hawley C. , Burke J. , Kausman J. , Hewitt I. , Parnham A. , Ford S. , Isbel N.
Published: August 2015

Background/Aim

This study aimed to report the clinical characteristics and outcomes of Australian patients treated with eculizumab for atypical haemolytic uraemic syndrome (aHUS).

Methods

A retrospective cohort study was undertaken of all patients in Australia treated with eculizumab provided in a compassionate access programme for a clinical diagnosis of aHUS using prospectively collected clinical data.

Results

A total of 10 patients with a median age of 23.5 years (interquartile range (IQR) 24.83 years) received compassionate access eculizumab for aHUS in Australia. Eight patients were female, and three had a family history of aHUS. Three received eculizumab for an initial acute aHUS presentation, three for relapsing and refractory acute aHUS, two for de novo aHUS post‐renal transplantation, and one each for aHUS recurrence post‐transplantation and facilitation of transplantation with a history of aHUS. The median duration of eculizumab therapy has been 911.5 days (IQR 569 days) with a cumulative exposure of 9184 days. At baseline all patients had renal and extra‐renal aHUS involvement, with up to three non‐renal organs affected. All but one patient, who died from uncontrollable gastrointestinal aHUS manifestations, have continued. The nine continuing patients achieved remission of aHUS. Two of the four patients requiring renal replacement therapy (RRT) at eculizumab commencement subsequently ceased RRT. Clinical events occurring in this cohort while on eculizumab treatment included neutropenia (two), posterior reversible encephalopathy syndrome (one), cardiomyopathy (one), pulmonary embolus (one), antibody‐mediated rejection resulting in renal graft failure (one), iron deficiency (one), gastrointestinal haemorrhage (one) and death (one).

Conclusion

Eculizumab has been an effective therapy for aHUS in this cohort, including when other therapies have failed.
Growth and geographical variation in the use of cardiac imaging in Australia
Authors: Fonseca R. , Otahal P. , Wiggins N. , Marwick T. H.
Published: August 2015

Background and Aim

Growth rates and regional differences in the use of cardiac imaging are potential metrics of quality of care. This study sought to define growth and regional variation in outpatient cardiac imaging in Australia.

Methods

Analyses are based on the rate of outpatient transthoracic echocardiography (TTE), transoesophageal echocardiography (TOE) and stress echocardiography (SE) and single‐photon emission computed tomography (SPECT) per 100 000 people in each geographic insurance region in Australia (Medicare local, ML). Numbers of tests from 2002 to 2013 were obtained from Medicare Australia Statistics, and the number of doctors was obtained from the Health Workforce data. Demographic data (total population, rural areas and quintiles of disadvantage) were obtained from census data.

Results

Over the past 11 years, TTE reimbursements/100 000 people increased from 1780 to 3497 (8.8% annualised growth), TOE from 33 to 61, SE from 181 to 947 and SPECT from 287 to 337. SE had the biggest increment, an average growth rate of 38.5%/year. The relationships between the use of each cardiac imaging techniques and demographic, medical and illness factors were analysed in outpatient tests reimbursed in 2012. For each additional medical practitioner per 1000 people, there was an increase in the rate of TTE (β = 1.25 (95% confidence interval CI: 1.17–1.33), P < 0.001), and TOE use (β = 1.13 (1.04–1.24), P = 0.005), independent of regional burden of cardiovascular disease and social determinants. For SPECT the largest independent correlate for testing was the percentage of women within the ML; each additional percentage increase resulted in doubling of the rate of testing (β = 2.25 (1.72–2.94), P < 0.001).

Conclusion

Variation in the use of TTE in Australia does not appear illness related and may be evidence of under‐ and overutilisation. An appropriate use process may contain this variation.
In response to the Commentary to our systematic review ‘Does adherence therapy improve medication adherence among patients with schizophrenia?’
Authors: Hegedüs Anna , Kozel Bernd
Published: August 2015

See response to the commentary by Grey R. et al.
Prioritarianism for Global Health Investments: Identifying the Worst Off
Authors: Sharp Daniel , Millum Joseph
Published: August 2015

The available resources for global health assistance are far outstripped by need. In the face of such scarcity, many people endorse a principle according to which highest priority should be given to the worst off. However, in order for this prioritarian principle to be useful for allocation decisions, policy‐makers need to know what it means to be badly off. In this article, we outline a conception of disadvantage suitable for identifying the worst off for the purpose of making health resource allocation decisions. According to our total advantage view: (1) the worst off are those who have the greatest total lifetime disadvantage; (2) advantage foregone due to premature death should be treated in the same way as other ways of being disadvantaged at a time; (3) how badly off someone is depends on the actual outcomes that will befall her without intervention, not her prospects at a time; and (4) all significant forms of disadvantage count for determining who is worst off, not just disadvantage relating to health. We conclude by noting two important implications of the total advantage view: first, that those who die young are among the globally worst off, and second, that the epidemiological shift in the global burden of disease from communicable to non‐communicable diseases should not lead to a corresponding shift in global health spending priorities.
Comorbid psychiatric conditions as mediators to predict later social adjustment in youths with autism spectrum disorder
Authors: Chiang Huey‐Ling , Gau Susan Shur‐Fen
Published: August 2015

Background

Individuals with autism spectrum disorder (ASD) experience long‐term social impairment and their comorbid psychiatric conditions negatively impact adaptive functioning. The aims of the study are to investigate whether comorbid psychopathologies, such as anxiety/depression, inattention, hyperactivity/impulsivity, and oppositional behaviors, mediated the link between autistic symptoms and social maladjustment.

Method

One hundred and twenty‐four youths diagnosed with a clinical diagnosis of DSM‐IV ASD (mean age, 10.6 ± 3.3 years) participated in this longitudinal study. They were assessed using semistructured diagnostic interviews on ASD and other psychiatric conditions at recruitment. Follow‐up interviews took place approximately 3 years later (37.59 ± 15 months) while the parents reported to the Social Adjustment Inventory for Children and Adolescents on their children's social adjustment. Mediation models were used to examine the mediating effect of comorbid psychopathologies on social adjustment.

Results

Youths with ASD had worse school, peer, and home functions than controls at follow‐up assessment. In general, comorbid psychiatric conditions mediated the link between autistic symptoms and different domains of social adjustment, independent of age, sex, and full‐scale IQ. Additionally, we found specific mediating effects of anxiety/depression and inattention on school functions; anxiety/depression on peer relationships; and oppositional behaviors on home behaviors.

Conclusion

Early comorbid psychopathologies may further impair later social adjustment in youths with ASD and an early identification and intervention of these comorbid conditions are suggested.
Disruptive viability selection on a black plumage trait associated with dominance
Authors: Acker P. , Grégoire A. , Rat M. , Spottiswoode C. N. , van Dijk R. E. , Paquet M. , Kaden J. C. , Pradel R. , Hatchwell B. J. , Covas R. , Doutrelant C.
Published: August 2015

Traits used in communication, such as colour signals, are expected to have positive consequences for reproductive success, but their associations with survival are little understood. Previous studies have mainly investigated linear relationships between signals and survival, but both hump‐shaped and U‐shaped relationships can also be predicted, depending on the main costs involved in trait expression. Furthermore, few studies have taken the plasticity of signals into account in viability selection analyses. The relationship between signal expression and survival is of particular interest in melanin‐based traits, because their main costs are still debated. Here, we first determined the main factors explaining variability in a melanin‐based trait linked to dominance: the bib size of a colonial bird, the sociable weaver Philetairus socius. We then used these analyses to obtain a measure representative of the individual mean expression of bib size. Finally, we used capture–recapture models to study how survival varied in relation to bib size. Variation in bib size was strongly affected by year and moderately affected by age, body condition and colony size. In addition, individuals bearing small and large bibs had higher survival than those with intermediate bibs, and this U‐shaped relationship between survival and bib size appeared to be more pronounced in some years than others. These results constitute a rare example of disruptive viability selection, and point towards the potential importance of social costs incurred by the dominance signalling function of badges of status.
Environmental impact of flooding: studies of ‘self‐cleaning’ of river ecosystem during consecutive flood events
Authors: Niedzielski P. , Skolasińska K. , Kozak L. , Kowalewski P. , Wachowiak W.
Published: August 2015

This article presents the similarities and differences between the chemical compositions of sediments deposited by theWarta river (central Poland) during two consecutive flood events. The studies conducted revealed significant differentiation in the metal content of acid‐leached sediment fractions deposited during the summer flood event and subsequent winter flood event. The lower metal content in the sediment deposits during the winter flood event may be evidence of different transport processes and sediment deposition during the consecutive flood stages; as well as the potential ‘purification’ of the river channel from pollutants previously deposited during the summer flood event.
Epigenetic silencing of NDRG2 promotes colorectal cancer proliferation and invasion
Authors: Hong Sung Noh , Kim Sung Jin , Kim Eun‐Ran , Chang Dong Kyung , Kim Young‐Ho
Published: August 2015

Background:

Genome‐wide methylation arrays have revealed aberrant methylation of N‐Myc downstream‐regulated gene 2 (NDRG2) promoter in colorectal cancer (CRC). This study investigated the role of NDRG2 in colorectal carcinogenesis.

Methods:

The aberrant promoter methylation, mRNA, and protein expression of NDRG2 were evaluated in 27 pairs of human CRC and adjacent normal tissues and seven human CRC‐derived cell‐lines. After stable NDRG2 over‐expressed RKO and DLD‐1 human CRC cell‐lines were constructed, in vitro functional assays, including colony formation, cell viability, proliferation, invasion and migration assays, and in vivo xenograft models were performed.

Results:

The promoter of NDRG2 was methylated in 89% human CRC tissue compared to adjacent normal colonic mucosa (7.4%; P < 0.001). High‐level methylation of NDRG2 promoter was more prevalent in proximal CRC (P = 0.022) and advanced T stage (P = 0.039). NDRG2 mRNA and protein expression was down‐regulated in 89% and 100% human CRC tissue, respectively. In human CRC cell‐lines, the promoter of NDRG2 was methylated aberrantly and mRNA, and protein expression of NDRG2 was down‐regulated. NDRG2 mRNA expression was reactivated by 5‐aza‐2′‐deoxycytidine. Colony formation of NDRG2 over‐expressing RKO cells was inhibited (P = 0.012), as was the viability, proliferation, and invasion of NDRG2 over‐expressing DLD‐1 cells (P < 0.001, P = 0.003, and P = 0.044, respectively). Tumor volume in xenograft mice transplanted with NDRG2 over‐expressing RKO and DLD‐1 cells was smaller than that in controls (P = 0.002 and P = 0.001, respectively).

Conclusions:

Epigenetic silencing of NDRG2 induces proliferation and invasion of CRC and may be associated with proximal CRC and advanced T stage. NDRG2 methylation might serve as novel biomarker of CRC.
Early decrement of serum carbohydrate antigen 19‐9 predicts favorable outcome in advanced pancreatic cancer
Authors: Chung Kwang Hyun , Ryu Ji Kon , Lee Ban Seok , Jang Dong Kee , Lee Sang Hyub , Kim Yong‐Tae
Published: August 2015

Background and Aim

The role of carbohydrate antigen 19‐9 (CA 19‐9) for predicting treatment outcome in pancreatic ductal adenocarcinoma (PDAC) remains to be elucidated. This study was aimed to determine the correlation between early decrement in CA 19‐9 concentration and prognosis of advanced PDAC after chemotherapy.

Methods

All patients confirmed with locally advanced or metastatic PDAC who received initial systemic chemotherapy for at least two cycles in our institution between January 2012 and December 2013 were included. Serum CA 19‐9 concentrations at baseline and 8 weeks after the initiation of chemotherapy were obtained. Correlation between CA 19‐9 decrement and survival outcomes (time to progression [TTP] and overall survival [OS]) were evaluated.

Results

A total of 183 patients with initially elevated CA 19‐9 were included. OS and TTP was significantly longer for patients whose serum CA 19‐9 concentration decreased more than 10% from baseline (n = 103), than that for patients whose serum CA 19‐9 was not decreased (n = 80) (423 vs 155 days, P < 0.001 for OS and 222 vs 75 days, P < 0.001 for TTP). In multivariate analysis, CA 19‐9 decrement more than 10% from baseline was still a significant factor for longer OS (hazard ratio for progression 0.275 [0.184–0.412], P < 0.001) and TTP (0.322 [0.219–0.473], P < 0.001) in both stage III and IV.

Conclusions

The early decrement of CA 19‐9 after the initiation of chemotherapy was an independent factor related with better survival outcomes in unresectable PDAC.
Microscopy of nanoparticulate dispersions
Authors: BRYDSON R. , BROWN A. , HODGES C. , ABELLAN P. , HONDOW N.
Published: August 2015

We present a critical review of the common methods for determining the dispersion state of nanoparticulate samples particularly in liquid media, including the determination of particle size and morphology; particle size distributions and polydispersity and equilibrium particle structure and chemistry. We highlight the potential contributions of both scanning probe and electron microscopies in this analysis which is of benefit in understanding nanoparticulate formulations and their behaviour applied across a very wide range of technologies and industry sectors.