bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a model to predict tyrosine kinase inhibitor‐sensitive EGFR mutations of non‐small cell lung cancer based on multi‐institutional data
Authors: Chang Hui , Liu Yuan‐Bin , Yi Wei , Lu Jia‐Bin , Zhang Jie‐Xia
Published: October 2018

Background

Non‐small cell lung cancer (NSCLC) with different EGFR mutation types shows distinct sensitivity to tyrosine kinase inhibitors (TKIs). This study developed a patho‐clinical profile‐based prediction model of TKI‐sensitive EGFR mutations.

Methods

The records of 1121 Chinese patients diagnosed with NSCLC from November 2008 to October 2014 (the development set) were reviewed. Multivariate logistic regression was conducted to identify any association between potential predictors and the classic sensitive EGFR mutations (exon 19 deletion and exon 21 L858R point mutation). A prediction index was created by assigning weighted scores to each factor proportional to a regression coefficient. Validation was made in an independent cohort consisting of 864 patients who were consecutively enrolled between November 2014 and January 2017 (the validation set).

Results

Seven independent predictors were identified: gender (female vs. male), adenocarcinoma (yes vs. no), smoking history (no vs. yes), N stage (N+ vs. N0), M stage (M1 vs. M0), brain metastasis (yes vs. no), and elevated Cyfra 21‐1 (no vs. yes). Each was assigned a number of points. In the validation set, the area under curve of the prediction index appeared as 0.698 (95% confidence interval 0.663–0.733). The sensitivity, specificity, positive and negative predictive values, and concordance were 95.0%, 32.3%, 61.4%, 85.1%, and 65.6%, respectively.

Conclusion

We developed a patho‐clinical profile‐based model for predicting TKI‐sensitive EGFR mutations. Our model may represent a noninvasive, economical choice for clinicians to inform TKI therapy.
Daily Drinking Is Associated with Increased Mortality
Authors: Hartz Sarah M. , Oehlert Mary , Horton AC , Grucza Richard A. , Fisher Sherri L. , Culverhouse Robert C. , Nelson Karl G. , Sumerall Scott W. , Neal Paul C. , Regnier Patrice , Chen Guoqing , Williams Alexander , Bhattarai Jagriti , Evanoff Bradley , Bierut Laura J.
Published: October 2018

Background

There is evidence that low‐level alcohol use, drinking 1 to 2 drinks on occasion, is protective for cardiovascular disease, but increases the risk of cancer. Synthesizing the overall impact of low‐level alcohol use on health is therefore complex. The objective of this paper was to examine the association between frequency of low‐level drinking and mortality.

Methods

Two data sets with self‐reported alcohol use and mortality follow‐up were analyzed: 340,668 individuals from the National Health Interview Survey (NHIS) and 93,653 individuals from the Veterans Health Administration (VA) outpatient medical records. Survival analyses were conducted to evaluate the association between low‐level drinking frequency and mortality.

Results

The minimum risk drinking frequency among those who drink 1 to 2 drinks per occasion was found to be 3.2 times weekly in the NHIS data, based on a continuous measure of drinking frequency, and 2 to 3 times weekly in the VA data. Relative to these individuals with minimum risk, individuals who drink 7 times weekly had an adjusted hazard ratio (HR) of all‐cause mortality of 1.23 (p < 0.0001) in the NHIS data, and individuals who drink 4 to 7 times weekly in the VA data also had an adjusted HR of 1.23 (p = 0.01). Secondary analyses in the NHIS data showed that the minimum risk was drinking 4 times weekly for cardiovascular mortality, and drinking monthly or less for cancer mortality. The associations were consistent in stratified analyses of men, women, and never smokers.

Conclusions

The minimum risk of low‐level drinking frequency for all‐cause mortality appears to be approximately 3 occasions weekly. The robustness of this finding is highlighted in 2 distinctly different data sets: a large epidemiological data set and a data set of veterans sampled from an outpatient clinic. Daily drinking, even at low levels, is detrimental to one's health.
Ethnic variations in the childhood prevalence of Hirschsprung disease in New Zealand
Authors: Taghavi Kiarash , Goddard Lucy , Evans Stephen M. , Hobson Andrew , Beasley Spencer W. , Sankaran Sasikumar , Kukkady Askar , Stevenson Jonathan , Stringer Mark D.
Published: October 2018

Background

Epidemiological studies have suggested that there may be ethnic variations in the prevalence of Hirschsprung disease (HD) but no study has systematically investigated this issue or potential ethnic variations in the extent of aganglionosis in HD. This study aimed to investigate this in a childhood population in New Zealand.

Methods

A multicentre national retrospective review was undertaken of all newly diagnosed cases of HD at each of the four paediatric surgical centres in New Zealand over a 16‐year period (January 2000 to December 2015). Original histological, radiological and operative reports were obtained and analysed. Self‐identified ethnicity was recorded from admission documents. Birth statistics were obtained from Statistics New Zealand.

Results

A total of 246 cases of HD were identified. The prevalence of HD was 1:3790 live births for European, 1:6610 among Māori, 1:1834 among Pacific Peoples, 1:3847 among Asian and 1:5694 among Middle Eastern. The prevalence of HD was statistically significantly greater in Pacific Peoples (P < 0.0005). The proportion of children with long‐segment HD was also significantly greater in Pacific and Asian populations than others (P = 0.04). These findings were not due to differences in the proportion of familial cases of HD among the different populations.

Conclusions

The prevalence and phenotype of HD varies significantly between different ethnic groups within New Zealand. This may well be related to variations in the frequencies of HD‐associated gene mutations within these populations.
Bursting the Bubble: Spatialising Safety for Privileged Migrant Women in Singapore
Authors: Cranston Sophie , Lloyd Jenny
Published: October 2018

This paper develops geographical work that is attentive to, and critical of, how safety is lived and narrated. In contrast to previous work on safety that focuses on fear, the paper looks at safety as something more than aspiration for women. To do so, the paper utilises the metaphor of the “expatriate bubble” to explore how safety is constructed and experienced by privileged migrants in Singapore. Utilising research from two projects, we argue that we need to think about how gender and Othering intersect to construct safety. In doing so, we explore how we can use conceptualisations of privileged migrants to research how safety can be understood and therefore practised more widely.
Requirements and Pitfalls of Dialyzer Sieving Coefficients Comparisons
Authors: Hulko Michael , Haug Ulrike , Gauss Julia , Boschetti‐de‐Fierro Adriana , Beck Werner , Krause Bernd
Published: October 2018

Sieving coefficients reported in dialyzer data sheets and instructions for use (IFUs) indicate the potential of different solutes to pass across a particular membrane. Despite being measured in vitro, sieving coefficient data are often used as a predictor of the clinical performance of dialyzers. Although standards for the measurement of sieving coefficients exist, the stated methodologies do not offer sufficient guidance to ensure comparability of test results between different dialyzers. The aim of this work was to investigate the relationship between sieving coefficients and published clinical performance indicators for two solutes, albumin loss and beta‐2 microglobulin (β2M) reduction ratio (RR), and to assess the impact of different in vitro test parameters on sieving coefficient values for albumin, β2M, and myoglobin. Clinical albumin loss and β2M RR for commercially available dialyzers used in hemodialysis (HD) and post‐dilution hemodiafiltration (HDF) were extracted from the literature and plotted against sieving coefficients reported in data sheets and IFUs. Albumin, β2M, and myoglobin sieving coefficients of a selection of dialyzers were measured per the ISO 8637 standard. The impact of in vitro testing conditions was assessed by changing blood flow rate, ultrafiltration (UF) rate, sampling time, and origin of test plasma. Results showed variation in albumin loss and β2M RR for the same sieving coefficient across different dialyzers in HD and HDF. Changes in blood flow rates, UF rates, sampling time, and test plasma (bovine vs. human) caused marked differences in sieving coefficient values for all investigated solutes. When identical testing conditions were used, sieving coefficient values for the same dialyzer were reproducible. Testing conditions have a marked impact on the measurement of sieving coefficients, and values should not be compared unless identical conditions are used. Further, variability in observed clinical data in part reflects the lack of definition of test conditions.
Postoperative management in cataract surgery: nepafenac and preservative‐free diclofenac compared
Authors: Ylinen Petteri , Taipale Claudia , Lindholm Juha‐Matti , Laine Ilkka , Holmström Emil , Tuuminen Raimo
Published: October 2018

Purpose

Current cataract surgery guidelines recommend routine use of topical nonsteroidal anti‐inflammatory drugs (NSAIDs) in preventing pseudophakic cystoid macular oedema (PCME). Here, we compare the clinical efficacy and tolerability of two potent NSAIDs, nepafenac and preservative‐free diclofenac following cataract surgery.

Methods

Randomized, double‐blind, prospective single‐centre study. Ninety‐six eyes of 95 patients undergoing routine cataract surgery were randomized 1:1 either to nepafenac (Nevanac, 1 mg/ml) or diclofenac (Dicloabak, 1 mg/ml) for 3 weeks. Seventy‐three patients accounting for 73 eyes completed the entire follow‐up. Aqueous flare and central retinal thickness (CRT) analysis were conducted preoperatively and at control visits 28 days and 3 months after surgery. A structured home questionnaire and interview were used to record any adverse effects of the topical medications, subjective visual recovery and the dispenser's ease of use.

Results

No differences were observed between the groups for aqueous flare, CRT, speed of recovery or visual acuity gain. Seven patients (16%) on nepafenac and 20 patients (48%) on preservative‐free diclofenac reported symptoms related to topical use of NSAID medications (p = 0.001).

Conclusion

No differences in clinical efficacy were found between potent NSAIDs, while tolerability might be an issue.
Morphological changes in the diseased retina on a healthy choroid‐retinal pigment epithelial complex after full macular translocation for exudative age‐related macular degeneration
Authors: van Romunde Saskia Helena Margaretha , Polito Antonio , Peroglio Deiro Antonio , Bertazzi Laura , Guerriero Massimo , Pertile Grazia
Published: October 2018

Purpose

To describe the change in the retinal morphology after full macular translocation (FMT) for exudative age‐related macular degeneration (AMD) and identify predictive factors for the visual outcome.

Methods

All patients who underwent FMT from December 2008 through July 2013 were selected. Exclusion criteria were FMT for other disease than AMD, age <60 years, <12 months of follow‐up or no available images. Spectral domain optical coherence tomography, fundus autofluorescence, fluorangiography and indocyanine green angiography were evaluated.

Results

In total, 51 patients were included with a mean follow‐up of 30 months. The presence of the external limiting membrane (ELM) was a significant predictor for a favourable visual outcome 1 year after FMT (OR = −0.30). Other significant predictive factors were the absence of intraretinal fluid (OR = 0.28) and the mixed choroidal neovascularization type (OR = −0.47), whereas nonresponders (OR = 0.41) and fibrotic lesions (OR = 0.35) were less likely to have a good visual function after surgery.

Conclusion

Full macular translocation (FMT), that permits to relocate the diseased macula onto an area of unaffected retinal pigment epithelial and choroid, can restore the anatomy and visual function in some patients with AMD when the outer retina layers are not irreversibly damaged. The presence of the ELM seems to be the most reliable factor in predicting the functional outcome.
Vitrectomy with silicone oil tamponade for retinal detachment associated with giant retinal tears: Favourable outcomes without adjuvant scleral buckling
Authors: Hocaoglu Mumin , Karacorlu Murat , Ersoz M. Giray , Sayman Muslubas Isil , Arf Serra
Published: October 2018

Purpose

To evaluate the outcomes of pars plana vitrectomy with silicone oil tamponade in the management of retinal detachment associated with giant retinal tears.

Methods

We reviewed 45 eyes of 42 patients with primary retinal detachment associated with giant retinal tears over 10 years at a tertiary referral centre. Patients underwent 23‐gauge vitrectomy without adjuvant scleral buckling by a single surgeon and had follow‐up at least 6 months after silicone oil removal.

Results

Mean follow‐up was 37 ± 35 months. Seven eyes (16%) had grade C proliferative vitreoretinopathy, and 16 (36%) had a giant retinal tear ≥180° at baseline. The primary reattachment rate was 84%, and the overall final anatomical success rate was 98%. The mean Snellen visual acuity equivalent at the final visit was 20/58. Final visual acuity ≥20/40 was achieved in 64%. The mean duration of silicone oil tamponade was 10.5 ± 4 weeks. By the final visit, silicone oil had been removed from 44 eyes (98%).

Conclusion

The high rates of anatomical and functional success support management of giant retinal tears‐associated retinal detachment with vitrectomy without adjuvant scleral buckling. Removal of silicone oil at the earliest possible time helps to avoid complications such as keratopathy, glaucoma and visual loss without apparent reason.
Superior outcome of corneal collagen cross‐linking using riboflavin with methylcellulose than riboflavin with dextran as the main supplement
Authors: Thorsrud Andreas , Hagem Anne Marie , Sandvik Gunhild Falleth , Drolsum Liv
Published: October 2018

Purpose

To compare the effect of corneal collagen cross‐linking (CXL) on progressive keratoconus using 0.1% riboflavin with either dextran or methylcellulose as the main supplement.

Methods

In a comparative case series, CXL was performed in 40 patients (40 eyes) using a riboflavin solution containing either dextran (dextran–riboflavin; n = 20) or methylcellulose (methylcellulose–riboflavin; n = 20). Changes in central corneal thickness (CCT), Scheimpflug tomography, maximal keratometry reading (Kmax), visual acuity (VA) and endothelial cell density (ECD) were recorded. Stromal changes one month after surgery were analysed using optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM).

Results

The CCT was significantly higher in the methylcellulose–riboflavin group during the CXL procedure. The IVCM demarcation line depth was 274 ± 80 (SD) μm in the dextran–riboflavin group and 442 ± 80 μm in the methylcellulose–riboflavin group (p < 0.001). Complete absence of keratocytes in the pre‐endothelial stroma was found in none of the corneas treated with dextran–riboflavin and in 42% of the corneas treated with methylcellulose–riboflavin. Visibility of the OCT demarcation line was significantly lower in the methylcellulose–riboflavin group. Kmax and corrected distance visual acuity were improved in the methylcellulose–riboflavin group and stable in the dextran–riboflavin group after 2 years. Endothelial cell density (ECD) was stable in both groups.

Conclusion

We found deeper structural changes in the methylcellulose–riboflavin group than in the dextran–riboflavin group. This may be explained by different riboflavin solution properties and raises safety concerns. The study also indicates improved effect using methylcellulose–riboflavin than dextran–riboflavin, possibly explained by deeper stromal CXL effect.
Letter: screening for adrenal suppression in paediatric inflammatory bowel disease
Authors: Wood P. , Henderson P.
Published: October 2018

Linked Content

This article is linked to Philpott et al papers. To view these articles visit https://doi.org/10.1111/apt.14573 and https://doi.org/10.1111/apt.14954.
Editorial: proton pump inhibitors (PPIs) and microscopic colitis
Authors: Krol Robin , van Oijen Martijn G. H.
Published: October 2018

Linked Content

This article is linked to Bonderup et al paper. To view this article visit https://doi.org/10.1111/apt.14916.
Letter: screening for adrenal suppression in paediatric inflammatory bowel disease – authors’ reply
Authors: Philpott Hamish , Dougherty Michael K. , Dellon Evan S.
Published: October 2018

Linked Content

This article is linked to Philpott et al and Wood and Henderson papers. To view these articles visit https://doi.org/10.1111/apt.14573 and https://doi.org/10.1111/apt.14861.
Editorial: a baseline tool for predicting response to peginterferon alfa‐2a in HBeAg‐positive patients—same score, different outcomes. Author's Reply
Authors: Chan Henry Lik Yuen
Published: October 2018

Linked Content

This article is linked to Chan et al and Peng papers. To view these articles visit https://doi.org/10.1111/apt.14862 and https://doi.org/10.1111/apt.14921.
Letter: proton pump inhibitors use and risk of hepatocellular carcinoma: A meta‐analysis of observational studies
Authors: Zhao Jian , Hua Li , Li Na , An Ran , Liang Chun
Published: October 2018

Linked Content

This article is linked Shao et al paper. To view this article visit https://doi.org/10.1111/apt.14835.
Letter: identifying coeliac disease among patients with bloating—Authors' reply
Authors: Hujoel Isabel A. , Rubio‐Tapia Alberto
Published: October 2018

Linked Content

This article is linked to Hujoel et al and Ellul papers. To view these articles visit https://doi.org/10.1111/apt.14625 and https://doi.org/10.1111/apt.14918.
Editorial: less acid, less cancer? Is this the question? Authors’ reply
Authors: Tan Mimi C. , Thrift Aaron P.
Published: October 2018

Linked Content

This article is linked to Tan et al and Triadafilopoulos and Singh papers. To view these articles visit https://doi.org/10.1111/apt.14895 and https://doi.org/10.1111/apt.14958.
To accept or not to accept: Level of moral concern impacts on tolerance of Muslim minority practices
Authors: Hirsch Magdalena , Verkuyten Maykel , Yogeeswaran Kumar
Published: October 2018

Living with diversity requires that we sometimes accept outgroup practices that we personally disapprove of (i.e., tolerance). Using an experimental design, we examined Dutch majority group members’ tolerance of controversial practices with varying degrees of moral concern, performed by a culturally dissimilar (Muslims) or similar (orthodox Protestant) minority group. Furthermore, we examined whether arguments in favour or against (or a combination of both) the specific practice impacted tolerance. Results indicated that participants expressed less tolerance for provocative practices when it was associated with Muslims than orthodox Protestants, but not when such practices elicit high degrees of moral concern. This indicates that opposition towards specific practices is not just a question of dislike of Muslims, but can involve disapproval of specific practices. Argument framing did not have a consistent effect on the level of tolerance for the practices.
Functional intronic variant of SLC5A10 affects DRG2 expression and survival outcomes of early‐stage non‐small‐cell lung cancer
Authors: Hong Mi Jeong , Yoo Seung Soo , Choi Jin Eun , Kang Hyo‐Gyoung , Do Sook Kyung , Lee Jang Hyuck , Lee Won Kee , Lee Jaehee , Lee Shin Yup , Cha Seung Ick , Kim Chang Ho , Lee Eung Bae , Cho Sukki , Jheon Sanghoon , Park Jae Yong
Published: October 2018

RegulomeDB is a new tool that can predict the regulatory function of genetic variants. We applied RegulomeDB in selecting putative functional variants and evaluated the relationship between these variants and survival outcomes of surgically resected non‐small‐cell lung cancer. Among the 244 variants studied, 14 were associated with overall survival (P < 0.05) in the discovery cohort and one variant (rs2257609 C>T) was replicated in the validation cohort. In the combined analysis, rs2257609 C>T was significantly associated with worse overall and disease‐free survival under a dominant model (P = 2 × 10−5 and P = 0.001, respectively). rs2257609 is located in the SLC5A10 intron, but RegulomeDB predicted that this variant affected DRG2, not SLC5A10 expression. The expression level of SLC5A10 was not different with the rs2257609 genotype. However, DRG2 expression was different according to the rs2257609 genotype (Ptrend = 0.03) and was significantly higher in tumor than in non‐malignant lung tissues (P = 1 × 10−5). Luciferase assay also showed higher promoter activity of DRG2 in samples with the rs2257609 T allele (P < 0.0001). rs2257609 C>T affected DRG2 expression and, thus, influenced the prognosis of early‐stage non‐small‐cell lung cancer. This study was approved by the Institutional Review Broad of Kyungpook National University of Hospital (Approval No. KNUMC 2014‐04‐210‐003).
Active K‐RAS induces the coherent rotation of epithelial cells: A model for collective cell invasion in vitro
Authors: Hirata Eishu , Ichikawa Takehiko , Horike Shin‐ichi , Kiyokawa Etsuko
Published: October 2018

At the invasive front of adenocarcinomas, single cells and multicellular structures exist; the latter include glands and cell clusters, such as tumor buddings and poorly differentiated clusters. Recent reports suggest the importance of collective cell migration in metastasis; however, it is technically difficult to observe the movement of multicellular structures in vivo. We utilized MDCK cells as a model for epithelial cells and established a method to quantify their motility in 3D structures in vitro. A single MDCK cell grows as a cell cluster in the gel and later proliferates and forms a cyst. Active K‐RAS expression induced rotation of both the cell clusters and the cysts. The rotation speed of cell clusters was 4 times higher than that of cysts. The screening of inhibitors for their effects on cell clusters and cysts revealed that cyclin B1 and β‐catenin were the key molecules for their rotation, respectively. Regulators for cyst rotation, such as vorinostat and β‐catenin, were not effective for inducing cell cluster rotation. These results indicate that the signaling pathways of cell dynamics are different between cell clusters and cysts. As cell clusters are related to lymph node involvement and the prognosis of various carcinomas, our in vitro quantitative system may be useful for the screening of drugs to prevent lymphatic invasion.
Langerhans cell histiocytosis in adults: Advances in pathophysiology and treatment
Authors: Kobayashi Masayuki , Tojo Arinobu
Published: October 2018

Langerhans cell histiocytosis (LCH) is a rare systemic disorder characterized by the accumulation ofCD1a+/Langerin+LCHcells and wide‐ranging organ involvement. Langerhans cell histiocytosis was formerly referred to as histiocytosis X, until it was renamed in 1987. Langerhans cell histiocytosis β was named for its morphological similarity to skin Langerhans cells. Studies have shown thatLCHcells originate from myeloid dendritic cells rather than skin Langerhans cells. There has been significant debate regarding whetherLCHshould be defined as an immune disorder or a neoplasm. A breakthrough in understanding the pathogenesis ofLCHoccurred in 2010 when a gain‐of‐function mutation inBRAF(V600E) was identified in more than half ofLCHpatient samples. Studies have since reported that 100% ofLCHcases showERKphosphorylation, indicating thatLCHis likely to be a clonally expanding myeloid neoplasm. Langerhans cell histiocytosis is now defined as an inflammatory myeloid neoplasm in the revised 2016 Histiocyte Society classification. Randomized trials and novel approaches have led to improved outcomes for pediatric patients, but no well‐defined treatments for adult patients have been developed to date. AlthoughLCHis not fatal in all cases, delayed diagnosis or treatment can result in serious impairment of organ function and decreased quality of life. This study summarizes recent advances in the pathophysiology and treatment of adultLCH, to raise awareness of this “orphan disease”.
Imatinib inhibits CSF1R that stimulates proliferation of rheumatoid arthritis fibroblast-like synoviocytes
Authors: Hu X , Tang J , Hu X , Bao P , Pan J , Ou Y , Deng W , Liang Y
Published: October 2018

In this study, we aimed to explore the effects of imatinib on the proliferation of rheumatoid arthritis synovial cell (RA-FLS) and inflammatory responses by regulating CSF1R. Differential genes were screened via microarray analysis, followed by being analysed through the weighted co-expression network (WGCNA) network, that included module and cluster analysis. The relationship between imatinib and genes was visualized using the Search Tool for the Retrieval of Interacting Genes (STITCH) database. Expressions of mRNA and protein were determined by reverse transcription–polymerase chain reaction (RT–PCR) and Western blot, respectively. Cell viability was examined via clone formation assay, while cell cycle and apoptosis were analysed through flow cytometry analysis. The hub gene CSF1R was ultimately determined by microarray analysis and WGCNA analysis. Colony-stimulating-factor receptor-1 (SF1R) was highly expressed in rheumatoid arthritis tissues and cells, and CSF1R over-expression could promote inflammatory responses. Moreover, CSF1R could promote RA-FLS proliferation, inhibit apoptosis and accelerate the cell cycle. The targeting relationship between imatinib and CSF1R was also validated in this study. Imatinib attenuated RA-FLS inflammation in a concentration-dependent manner. Meanwhile, imatinib could inhibit RA-FLS proliferation and promote apoptosis, ultimately reducing the damage of RA-FLS. Over-expression of CSF1R accelerated the cell cycle and proliferation of RA-FLS, while inhibiting cell apoptosis. Conversely, imatinib could significantly restrain the cell cycle and viability of RA-FLS and accelerated apoptosis via suppression of CSF1R expression. Further, histological and serological assay investigated and proved the proinflammatory effects of CSF1R in RA rabbits.
QRICH1 mutations cause a chondrodysplasia with developmental delay
Authors: Lui Julian C. , Jee Youn Hee , Lee Audrey , Yue Shanna , Wagner Jacob , Donnelly Deirdre E. , Vogt Karen S. , Baron Jeffrey
Published: October 2018

In many children with short stature, the etiology of the decreased linear growth remains unknown. We sought to identify the underlying genetic etiology in a patient with short stature, irregular growth plates of the proximal phalanges, developmental delay, and mildly dysmorphic facial features. Exome sequencing identified a de novo, heterozygous, nonsense mutation (c.1606C>T:p.R536X) in QRICH1. In vitro studies confirmed that the mutation impaired expression of the QRICH1 protein. SiRNA‐mediated knockdown of Qrich1 in primary mouse epiphyseal chondrocytes caused downregulation of gene expression associated with hypertrophic differentiation. We then identified an unrelated individual with another heterozygous de novo nonsense mutation in QRICH1 who had a similar phenotype. A recently published study identified QRICH1 mutations in three patients with developmental delay, one of whom had short stature. Our findings indicate that QRICH1 mutations cause not only developmental delay but also a chondrodysplasia characterized by diminished linear growth and abnormal growth plate morphology due to impaired growth plate chondrocyte hypertrophic differentiation.
Remaking the world in our own image: vulnerability, resilience and adaptation as historical discourses
Authors: Bankoff Greg
Published: October 2018

A warming climate and less predictable weather patterns, as well as an expanding urban infrastructure susceptible to geophysical hazards, make the world an increasingly dangerous place, even for those living in high‐income countries. It is an opportune moment, therefore, from the vantage point of the second decade of the twenty‐first century, to review the terms and concepts that have been employed regularly over the past 50 years to assess risk and to measure people's exposure to such events in the light of the wider geopolitical context. In particular, it is useful to examine ‘vulnerability’, ‘resilience’, and ‘adaptation’, the principal theoretical concepts that, from an historical perspective, have dominated disaster studies since the end of the Second World War. In addition, it is valuable to enquire as to the extent to which such discourses were ideological products of their time, which sought to explain societies and their environments from the stance of competing conceptual frameworks.
Apolipoprotein E gene polymorphisms: a risk factor for preterm brain injury?
Authors: Vollmer Brigitte
Published: October 2018

This commentary is on the original article by Dzietko et al. on pages
337–342 of this issue.
Effectiveness of high‐intensity interval training combined with resistance training versus continuous moderate‐intensity training combined with resistance training in patients with type 2 diabetes: A one‐year randomized controlled trial
Authors: Magalhães João P. , Júdice Pedro B. , Ribeiro Rogério , Andrade Rita , Raposo João , Dores Hélder , Bicho Manuel , Sardinha Luís B.
Published: October 2018

Aims

To evaluate the impact of one‐year high intensity interval training (HIIT) combined with resistance training (RT) vs continuous moderate intensity training (MCT) combined with RT on glycaemic control, body composition and cardiorespiratory fitness (CRF) in patients with type 2 diabetes.

Materials and Methods

A randomized controlled trial included 96 participants with type 2 diabetes for a one‐year supervised exercise intervention with three groups: Control, HIIT with RT and MCT with RT). The control group received standard counseling regarding general PA guidelines, with no structured exercise sessions. The main outcome variable was HbA1c (%). Secondary outcomes were other glycaemic variables, body composition, anthropometry measurements, CRF and enjoyment of exercise. Generalized estimating equations (GEE) were used to model outcomes.

Results

Among the 96 participants enrolled in the intervention, 80 were randomized, with a mean (SD) age of 58.5 years (7.7) and a mean HbA1c of 7.2% (1.6). After adjusting the model for sex and total moderate‐to‐vigorous physical activity (MVPA), we found that both the MCT with RT (β, 0.003; P, 0.921) and the HIIT with RT (β, 0.025; P, 0.385) groups had no effect on HbA1c. A favourable effect was observed in the MCT with RT group, with a reduction in whole body fat index (β, −0.062; P, 0.022), android fat index (β, −0.010; P, 0.010) and gynoid fat index (β, −0.013; P, 0.014). Additionally, CRF increased during the intervention, but only in the MCT with RT group (β, 0.185; P, 0.019).

Conclusions

The results from this study suggest that there was no effect of either MCT with RT or HIIT with RT on glycaemic control in individuals with type 2 diabetes. However, the combination of MCT and RT improved body composition and CRF following a one‐year intervention.
Does protectionism harm unskilled workers?
Authors: Beladi Hamid , Marjit Sugata , Oladi Reza
Published: October 2018

In this paper we construct a general equilibrium model of trade and illustrate that return to unskilled labor may be negatively correlated with the price of product it produces. Specifically, we show that greater protection for the intermediate good that uses “unskilled” labor can reduce the unskilled wages. This result has interesting political‐economic implications.
Septic pyomyositis, multiple pelvic osteomyelitis and thrombosis in a Thoroughbred foal
Authors: Pressanto M. C. , Beccati F. , Stefanetti V. , Passamonti F. , Pilati N. , Pepe M.
Published: October 2018

Multiple septic osteomyelitis, septic thrombi and septic arthritis are recognised as possible complications of sepsis; however, there are few reports of localised pyomyositis in association with septic arterial thrombosis in foals. A 1‐month Thoroughbred colt was presented for investigation of acute and progressive left hindlimb lameness. Physical and laboratory examinations were performed. Ultrasonographic, radiographic and computed tomographic examinations revealed the presence of multiple abscesses and areas of osteomyelitis localised to the gluteal muscles, coxal bone and lumbar spine respectively. Considering the poor prognosis, the foal was subjected to euthanasia. Necropsy confirmed the diagnostic imaging findings and revealed the presence of an extensive septic thrombus, affecting the internal iliac artery, and a single pulmonary abscess. Streptococcus equi subsp. zooepidemicus was isolated from all lesions.
False “Facts” and Faulty Thinking
Authors: Duffy Bobby
Published: October 2018

In an excerpt from The Perils of Perception, Bobby Duffy argues that our brains are partly to blame for our misperceptions about society
Zachary Macaulay: The Statistician Who Fought to end Slavery in British Colonies
Authors: Scarrott Diana
Published: October 2018

Diana Scarrott presents a brief history of the “brilliant statistician” of the British abolition movement
Notebook: The Laplace Distribution
Authors: Geraci Marco , Borja Mario Cortina
Published: October 2018

When studying the same object, different scientists and scientific instruments can produce widely divergent measurements. Marco Geraci and Mario Cortina Borja describe a probability distribution to model observations when heterogeneity and large errors are present
Statistics in Court
Authors: Thieme Nick
Published: October 2018

Judges and jurors are often asked to make sense of statistics. But data, probabilities and uncertainties are easily misunderstood or misused by those not trained to deal with them. Is education the answer? Or is greater oversight required? Nick Thieme considers the options
Cooking up Statistics: The Science and the Art
Authors: Smith Letisha
Published: October 2018

Letisha Smith – winner of the 2018 Award for Statistical Excellence in Early-Career Writing – started the year with the resolve to eat smarter, with less food and less money going to waste. She turned to machine learning to help streamline her meal plans
Glass‐forming region and enhanced Bi NIR emission in sodium tantalum silicate laser glass
Authors: Peng Jie , Cao Jiangkun , Tan Linling , Peng Mingying
Published: October 2018

Bismuth (Bi)‐doped glasses and fibers are of current interest as promising active media for new fiber lasers and amplifiers due to their 800‐1700 nm near‐infrared (NIR) emission. However, the optically active Bi centers in silica are easily volatilized during high‐temperature fiber drawing, which results in low Bi doping concentration and low gain NIR luminescence. Here, we explored the glass‐forming region in a model glass system of sodium tantalum silicate (Na2O‐Ta2O5‐SiO2) glass and attained suitable glass host for enhancing Bi NIR emission, right followed by detailed analysis on optical and structural characterization. Glass‐forming region roughly lies in where Ta2O5 ≤ 30 mol%, SiO2 ≥ 40 mol%, and Na2O ≤ 40 mol%. Not only is glass‐forming ability improved but also Bi NIR emission is enhanced (~60 times) by the introduction of Ta into glass network. Dissociated Na cations are restricted beside Ta, the high‐field‐strength element, so that the negative impacts of Na cations on glass formation and Bi NIR emission are weakened, which is responsible for the highly enhanced Bi NIR emission. This work helps us understand the glass‐forming of tantalum silicate glass systems and luminescent behaviors of Bi. Hopefully, it could contribute to designing the Bi‐doped laser glasses and high gain fibers with stable luminescent properties in future.
Microwave heating controlled reactive melt infiltration for graphite‐Si‐SiC ceramics manufacturing
Authors: Cornolti Luca , Martinelli Simone , Bianchi Giovanni , Ortona Alberto
Published: October 2018

In this work, we investigated a procedure which exploits microwave ovens to produce SiC‐ based components by reactive melt infiltration of silicon into graphite preforms. The employed oven is designed to grant optical access to the sample surface, which allows to measure its temperature evolution though a noncontact pyrometer. This signal was used as a feedback to control the power provided to the preform and as an experimental output whose analysis provides insight into the reaction mechanism. Specifically, it is found that complete infiltration is achieved much before the end of the reaction. The latter is not fully self‐sustained as the global reaction rate continuously decreases with time until it is no more able to keep the temperature above the silicon solidification value. At that point, the reaction stops. The analysis of the processed samples proved that this procedure allows producing fully infiltrated samples without material failure by adjusting the heat provided during the infiltration stage rather than by tuning the preform structure and composition, which is the usual approach. The proposed method is less time and energy consuming than the standard one.
Seasonal aggregation and diel activity by the sicklefin devil ray Mobula tarapacana off a small, equatorial outcrop of the Mid‐Atlantic Ridge
Authors: Mendonça Sibele A. , Macena Bruno C. L. , Afonso André S. , Hazin Fabio H. V.
Published: October 2018

The present study aimed to analyse occurrence patterns, relative abundance and habitat use by the sicklefin devil ray Mobula tarapacana in the Saint Peter and Saint Paul Archipelago (SPSPA), Brazil, located in the Mid‐Atlantic Ridge. Sampling was conducted between December 2008 and December 2012 by surface surveys and tagging with conventional tags and acoustic transmitters. Mobula tarapacana were sighted in the SPSPA year round but the highest frequency of occurrence was observed from January to June, probably due to greater food availability during this season. However, M. tarapacana might also use the area for reproductive purposes based on evidence of mating behaviour. The residency period of tagged rays measured by three autonomous acoustic receivers deployed around SPSPA spanned from 1 to 74 days with most of the detections occurring during daytime. These results suggest that the SPSPA could be an ecologically‐important aggregation area for M. tarapacana, possibly providing the species with a feeding or resting habitat while transiting in the equatorial Atlantic Ocean.
Experimental study on the static mechanical properties of a milled mixture of sugar cane
Authors: Duan Qing Shan , Mao Han Ling , Li Xin Xin , Mao Han Ying , Huang Zhen Feng , Li Bing
Published: October 2018

The mechanical properties of a milled mixture of sugar cane are the basis for the establishment of a milled mixture mechanical model and the constitutive relation under different loading conditions. In this article, the static mechanical properties of the milled mixture were revealed using uniaxial confined compression, uniaxial loading‐unloading, and consolidated‐drained triaxial and direct shear tests. Axial stress is a cubic polynomial relating to the compression ratio. The Young's modulus is proportional to the loading pressure. The void ratio is exponentially related to the stress, and the compression and swelling indices are 4.273 and 0.184, respectively, in the loading‐unloading process from 0.208 to 1.389 MPa. Shear failure does not occur when the axial strain is less than or equal to 25%. Shear failure obeys the Mohr–Coulomb law, and the cohesive force and internal friction angle are 10.16 kPa and 31.5°, respectively. Other key parameters were obtained. All of these provided the basis for constructing the constitutive model of a milled mixture of sugar cane.

Practical applications

In this article, the prepared cane and bagasse are collectively called the milled mixture of sugar cane, which includes solid fiber, juice, and air. In the milling process, the three components in the milled mixture of sugar cane interact; the coupling of solid fiber and juice is particularly important. The mechanical properties of the milled mixture of sugar cane are the basis for the establishment of a milled mixture mechanical model and the constitutive relation under different loading conditions. In this article, the static mechanical properties of the milled mixture were revealed using uniaxial confined compression, uniaxial loading–unloading, and consolidated‐drained triaxial and direct shear tests. The key parameters were obtained. These rules and data improved the understanding of the stress–strain relationship of the milled mixture of sugar cane during the milling process and provided the basis for constructing the constitutive model of the milled mixture.
Qualitative investigation of meat species in meat products by real time polymerase chain reaction
Authors: Ghajarbeygi P. , Mahmoudi R. , Jafari Jozani R. , Pakbin B.
Published: October 2018

Identification of meat species in processed meat products is a major problem in meat technology to produce safe and standard meat products. The aim of this study was identification of meat species in meat processed products including sausages and burgers. The study was carried out by targeting a conserved region of mitochondrial DNA and by using Real‐Time polymerase chain reaction (RT‐PCR) method. Sampling procedure consisted of different types of commercial meat products including susages, burgers, and salamis which were collected from different stores in Qazvin province‐Iran. After DNA extraction, RT‐PCR assay was performed to detect specific DNA sequences of animal species in meat product samples. Specific DNA sequences for chicken, horse, camel, beef, and turkey meat were detected successfully in collected samples. Consequently, we found in this study that RT‐PCR method is a very powerful and easy method for monitoring commercial meat products based on conserved region of mitochondrial DNA.

Practical applications

Recently, adulteration in formulation of meat products such as burger and sausages is the principle problem in this industry. Meat species used in this category of products are varied according to type of adulteration and final product. Separately, safety of meat products is dependent on the formulation and the raw materials including meat species used for manufacturing of formulated meat products. In this study, identification of meat species in burger and sausage samples collected from different local stores in Qazvin Province, Iran was performed by Real‐Time PCR. This molecular method is a very practical, rapid, precise, sensitive, and useful method for identification of meat species in these products. Chicken, horse, camel, beef, and turkey meat were detected successfully in the collected samples. Also, the quality and adulteration of the collected meat product samples have been determined for the future development of health and quality strategies and investigations.
Self‐Reported Physical Function As a Predictor of Hospitalization in the Lifestyle Interventions and Independence for Elders Study
Authors: Callahan Kathryn E. , Lovato Laura , Miller Michael E. , Marsh Anthony P. , Fielding Roger A. , Gill Thomas M. , Groessl Erik J. , Guralnik Jack , King Abby C. , Kritchevsky Stephen B. , McDermott Mary M. , Manini Todd , Newman Anne B. , Rejeski W. Jack
Published: October 2018

Objectives

To explore whether baseline scores on the Mobility Assessment Tool—short form (MAT‐sf), a brief, animated, computer‐based means of assessing mobility that predicts mobility disability, are associated with number of hospitalizations and time to first hospitalization over a median follow‐up of 2.7 years.

Design

Post hoc analysis of prospectively gathered data from the Lifestyle Interventions and Independence for Elders (LIFE) Study, a randomized clinical trial of lifestyle interventions to preserve mobility in older adults.

Setting

Eight U.S. academic medical centers.

Participants

Of 1,635 sedentary community‐dwelling older adults enrolled in LIFE, 1,574 completed baseline physical function screening including the MAT‐sf, with baseline scores ranging from 30.2 (low function) to 69.8 (high function) on a scale from 30 to 80.

Measurements

Number of hospitalizations and time to first hospitalization, adjusted for age, sex, race, living alone, clinical site, baseline comorbidities, number of prescription medications, and cognition.

Results

Of the 1,557 participants with data regarding hospitalization status, 726 (47%) had at least 1 hospitalization; 78% of these had 1 or 2 hospitalizations. For every 10‐point lower MAT‐sf score, the rate of all hospitalizations was 19% higher in those with lower scores (adjusted rate ratio=1.20, 95% confidence interval (CI)=1.08–1.32, p<.001). Lower baseline MAT‐sf scores were also associated with greater risk of first hospitalization (adjusted hazard ratio=1.20, 95% CI=1.09–1.32, p<.01, per 10‐point lower MAT‐sf score).

Conclusion

Low MAT‐sf scores identify older adults at risk of hospitalization; further study is needed to test interventions to reduce hospitalizations in these individuals.
Implementing “Patient‐Centered Care”: A Revolutionary Change in Health Care Delivery
Authors: Applegate William B. , Ouslander Joseph G. , Kuchel George A.
Published: October 2018

This editorial comments on the article by Blaum et al and Naik et al
Applying the Technology Choice Model in Consequential Life Cycle Assessment: A Case Study in the Peruvian Agricultural Sector
Authors: Larrea‐Gallegos Gustavo , Vázquez‐Rowe Ian , Wiener Hugo , Kahhat Ramzy
Published: October 2018

Demand for grapes to produce pisco in southern‐coastal Peru is expected to double by 2030. However, the appellation of this beverage confines the production and limits the space for agricultural expansion, leading to a situation in which potential competition for resources with established constraints is foreseen. Hence, the objective of this study is to understand the environmental impacts, focused on climate change and water consumption, linked to the agricultural dynamism in the valleys of Ica and Pisco due to an increase in the demand of pisco. For this, the viticulture system was analyzed regarding predicted changes in terms of expansion, displacement or intensification using a consequential life cycle assessment (CLCA) approach, identifying the environmental consequences of these shifts. A two‐step CLCA model was used based on the results of a previous attributional study, in which marginal effects were estimated following the stochastic technology‐of‐choice model (STCM) operational framework. Results identified a potential for the increase of pisco production based on crop substitution in the valleys of Ica and Pisco and suggest that greenhouse gas emissions and water consumption will be reduced locally, but the displaced agricultural production would reverse this tendency. Regardless of the policy implications of the results in the analyzed system, the proposed methodology constitutes a robust methodology that can be applied to other highly constrained agricultural systems, namely, those regulated by geographic indications.