bluuebunny/crossref_metadata_2025 huggingface dataset:
When does extreme drought elicit extreme ecological responses?
Authors: Zhang Fangyue , Quan Quan , Ma Fangfang , Tian Dashuan , Hoover David L. , Zhou Qingping , Niu Shuli
Published: June 2019

Global climate change models predict an increase in the frequency and intensity of extreme droughts, with uncertain ecological impacts across ecosystems. In particular, it is not clear when extreme droughts will elicit extreme ecological responses.

For this study, we employed three complementary approaches to explore the relationships between extreme drought and ecosystem responses. First, we used global data mining to evaluate the relationship between extreme gross primary productivity and extreme precipitation from 1980 to 2013. Second, we conducted a meta‐analysis using 132 drought experiments across the globe to assess the response ratios (RRs) of above‐ground net primary productivity (ANPP) to extreme versus non‐extreme drought treatments. Third, we examined community and ecosystem responses in an alpine meadow to a drought gradient experiment, which included five precipitation treatment levels (1/12 P, 1/4 P, 1/2 P, 3/4 P, and P, where P is the growing season precipitation).

This study had three key results. In our historical data mining, we found that extreme droughts elicited extreme ecological responses only 15.1% of the time. The meta‐analysis results indicated that there were no significant differences in the RRs of ANPP between the extreme versus non‐extreme drought treatments. The drought gradient experiment results revealed that although the four drought treatments were statistically extreme, only the most extreme drought treatment (1/12 P) significantly reduced ANPP over the 3 years. Meanwhile, species richness and asynchrony were significantly reduced under the 1/12 P treatment, which led to a significant reduction in productivity.

Synthesis. These results suggest that extreme ecological responses to extreme drought may be less frequent than previously thought. But when they do occur, extreme ecological responses may be driven by plant community changes such as species asynchrony, species loss or species reordering. Our experimental results highlight the key role of community dynamics in determining the resistance of ecosystem productivity to extreme drought, which should be assessed when predicting ecological responses to climate change.
Adaptation to host in Vibrio vulnificus, a zoonotic pathogen that causes septicemia in fish and humans
Authors: Hernández‐Cabanyero Carla , Lee Chung‐Te , Tolosa‐Enguis Verónica , Sanjuán Eva , Pajuelo David , Reyes‐López Felipe , Tort Lluis , Amaro Carmen
Published: June 2019

Vibrio vulnificus is a siderophilic pathogen spreading due to global warming. The zoonotic strains constitute a clonal‐complex related to fish farms that are distributed worldwide. In this study, we applied a transcriptomic and single gene approach and discover that the zoonotic strains bypassed the iron requirement of the species thanks to the acquisition of two iron‐regulated outer membrane proteins (IROMPs) involved in resistance to fish innate immunity. Both proteins have been acquired by horizontal gene transfer and are contributing to the successful spreading of this clonal‐complex. We have also discovered that the zoonotic strains express a virulent phenotype in the blood of its main susceptible hosts (iron‐overloaded humans and healthy eels) by combining a host‐specific protective envelope with the common expression of two toxins (VvhA and RtxA1), one of which (RtxA1) is directly involved in sepsis. Finally, we found that both IROMPs are also present in other fish pathogenic species and have recently been transmitted to the phylogenetic lineage involved in human primary sepsis after raw seafood ingestion. Together our results highlight the potential hazard that the aquaculture industry poses to public health, which is of particular relevance in the context of a warming world.
Care of Women Presenting with Suspected Preterm Prelabour Rupture of Membranes from 24+0 Weeks of Gestation
Authors: Thomson AJ ,   the Royal College of Obstetricians and Gynaecologists
Published: June 2019

Tweetable abstract

#GreenTopGuideline No. 73 recommends how to diagnose & care for suspected #PPROM from 24 + 0 to 36 + 6 weeks of gestation.
Implementation study reporting diagnostic accuracy, outcomes and costs in a multicentre randomised controlled trial of non‐expert lung ultrasound to detect pulmonary oedema
Authors: Baker Kylie , Brierley Stephen , Kinnear Frances , Isoardi Katherine , Livesay Georgia , Stieler Geoffrey , Mitchell Geoffrey
Published: June 2019

Background

Lung ultrasound experts claim that ‘B line’ artefacts herald pulmonary oedema, but links between early recognition and improved outcome are unconfirmed, particularly for non‐expert clinicians.

Objective

Assess individual and system impacts of early, non‐expert lung ultrasound (LUS) in breathless older patients.

Methods

Prospective single‐blinded randomised controlled trial of point of care LUS by non‐expert clinicians, augmenting ED assessment of patients over 60 years, presenting with dyspnoea. After brief training, clinicians at three hospitals used computer‐generated block randomisation envelopes to allocate a convenience sample of consenting presenters to conventional or LUS‐augmented management. ED provisional diagnosis was compared to a post‐discharge chart audit diagnosis, blinded to ultrasound findings. Secondary outcomes were the length of stay in ED and hospital, costs and discharge destinations.

Results

From three sites, 224 controls were compared with 218 interventions. LUS improved diagnostic accuracy, with a small effect size in favour of LUS (risk difference: 6.5%, 95% CI 0.9–12) and a number needed to scan of 16 (95% CI 8–107). With LUS, ED and hospital stay increased non‐significantly, while discharge destination trends improved. No harm ensued.

Conclusions

Non‐expert LUS augmenting dyspnoea workup may improve diagnostic accuracy, but did not significantly alter costs or outcomes in the ED or the hospital. Trial registration: Australia and New Zealand Clinical Trials Registry (ACTRN12613001023741).
Sarcopenia, nutritional status and type 2 diabetes mellitus: A cross‐sectional study in a group of Mexican women residing in a nursing home
Authors: Velázquez‐Alva María C. , Irigoyen‐Camacho María E. , Zepeda‐Zepeda Marco A. , Lazarevich Irina , Arrieta‐Cruz Isabel , D'Hyver Carlos
Published: June 2019

Aim

To evaluate the prevalence of sarcopenia and its association with nutritional status and type 2 diabetes mellitus (T2DM) in older women living in a nursing home.

Methods

This cross‐sectional study assessed nutritional status using the Mini Nutritional Assessment (MNA). Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People; hand grip strength and physical performance were determined by dynamometry and gait speed, respectively. Muscle mass was assessed using calf circumference.

Results

The mean age of the 114 participants was 84.1 ± 7.0 years. The prevalence of sarcopenia and T2DM was 30.7% and 10.5%, respectively. The majority (66.7%) had a normal nutritional status, 29.8% were at risk of malnutrition, and 3.5% were undernourished. The prevalence of sarcopenia in participants at risk of malnutrition and those who were undernourished was higher compared with participants with a normal NS (P < 0.0001). A statistically significant difference was observed in the Barthel Index (BI) between women with and without sarcopenia (P = 0.048). The multivariate logistic regression model, adjusted by age (p = 0.007) showed an association between sarcopenia and nutritional status. Women with a poor nutritional status were more likely to have sarcopenia (OR 4.97, P = 0.003) whilst those with T2DM showed a higher probability of sarcopenia (OR 5.52, P = 0.019) than women without T2DM.

Conclusions

Sarcopenia was highly prevalent in women with a poor nutritional status and T2DM. It is necessary to implement intervention programs to reduce adverse outcomes.
Tissue‐Specific Distribution of Sphingomyelin Species in Pork Chop Revealed by Matrix‐Assisted Laser Desorption/Ionization–Imaging Mass Spectrometry
Authors: Enomoto Hirofumi , Takeda Shiro , Hatta Hajime , Zaima Nobuhiro
Published: June 2019

Sphingomyelin (SM) species are major sphingolipids in pork meat that affect quality parameters, such as health benefits due to their protective properties against chronic diseases; however, their spatial distribution remains unclear. We used matrix‐assisted laser desorption/ionization (MALDI)–imaging mass spectrometry (IMS) to investigate the distribution and composition of SM species in pork chop consisting of longissimus thoracis et lumborum muscle (loin), intermuscular fat tissue, transparent tissue, and spinalis muscle. Four SM species were identified by liquid chromatography–electrospray ionization–tandem MS (MS/MS) and MALDI–MS/MS and visualized using MALDI–IMS. SM species containing stearic acid were predominantly distributed in the loin and spinalis muscle, whereas SM species containing palmitic, lignoceric, and nervonic acids were predominantly distributed in transparent tissue. These results indicated that the distribution of SM species differed among the pork tissues, depending on the tissue‐specific fatty acid composition. The total amount including all identified SM species was higher in the loin than in spinalis muscle. Pork is reportedly associated with increased risk for chronic diseases due to the high amount of heme iron. From the observation of color, the amount of heme iron was lower in loin than in spinalis muscle. Thus, the degree of risk for chronic diseases might be lower in the loin than in spinalis muscle. This is the first report on the tissue‐specific distribution of SM species in meat at a microscopic resolution using IMS. MALDI–IMS analysis may be useful in assessing the association between SM species and quality parameters of pork meat.

Practical Application

Sphingomyelin (SM) species are major sphingolipids in pork meat. SM species affect quality parameters such as health benefits due to their protective properties against colon cancer and atherosclerosis. Matrix‐assisted laser desorption/ionization–imaging mass spectrometry analysis combined with liquid chromatography–electrospray ionization‐tandem mass spectrometry is a suitable method to directly investigate the distribution and composition of SM species at microscopic level among different tissues of pork meat. Therefore, this method is useful to assess the SM species‐induced health effect of different tissues of pork meat.
Does intraperitoneal ropivacaine reduce postoperative inflammation? A prospective, double‐blind, placebo‐controlled pilot study
Authors: Hayden Jane , Gupta Anil , Thörn Sven‐Egron , Thulin Pontus , Block Linda , Oras Jonatan
Published: June 2019

Background

Postoperative inflammation is a common consequence of surgery and the ensuing stress response. Local anesthetics have anti‐inflammatory properties. The primary aim of this study was to evaluate if LA administrated intraperitoneally perioperatively might inhibit expression of inflammatory cytokines.

Methods

This was a, randomized, double blind, placebo‐controlled study (ClinicalTrial.gov reg no: NCT02256228) in patients undergoing surgery for ovarian cancer. Patients were randomized to receive: intraperitoneal ropivacaine (Group IPLA) or saline (Group P) perioperatively. Except for study drug, patients were treated similarly. At the end of surgery, a multi‐port catheter was inserted intraperitoneally, and ropivacaine 2 mg/mL or 0.9% saline, 10 mL was injected intermittently every other hour during 72 hours postoperatively. Systemic expression of cytokines and plasma ropivacaine were determined before and 6, 24, and 48 hours after surgery. Stress response was measured by serum glucose, cortisol, and insulin.

Results

Forty patients were recruited, 20 in each group. There was no statistical significant difference in systemic cytokine between the groups at any time point. Serum cortisol was significantly lower in the IPLA group at 6 hours, median 103 nmol/L (IQR 53‐250) compared to placebo, median 440 nmol/L (IQR 115‐885), P = 0.023. Serum glucose and insulin were similar between the groups. Total and free serum concentrations of ropivacaine were well below toxic concentrations.

Conclusion

In this small study, perioperative intraperitoneal ropivacaine did not reduce the systemic inflammatory response associated with major abdominal surgery. Total and free ropivacaine concentrations were below known toxic concentrations in humans.
Genetic polymorphisms and prediction of chronic post‐surgical pain after hysterectomy—a subgroup analysis of a multicenter cohort study
Authors: Hoofwijk Daisy M. N. , van Reij Roel R. I. , Rutten Bart P. F. , Kenis Gunter , Theunissen Maurice , Joosten Elbert A. , Buhre Wolfgang F. , van den Hoogen Nynke J.
Published: June 2019

Background

Chronic post‐surgical pain (CPSP) is a serious problem. Clinical and psychological variables have not been able to explain all observed variance in prevalence and severity of CPSP. The first objective is to determine the association between genetic polymorphisms and the prevalence of CPSP after hysterectomy. The second objective is to analyze if the implementation of genetic polymorphisms into a previously performed clinical and psychological predictor analysis on the development of CPSP after hysterectomy will improve its discriminatory power.

Methods

A prospective multicenter cohort study was performed in patients undergoing hysterectomy for benign indication. Clinical and psychological variables were collected by questionnaires in the week before surgery, post‐operatively up to day 4, 3 and 12 months after hysterectomy. Blood was collected and 16 polymorphisms previously suggested to be correlated to CPSP (COMT, GCH1, KCNS1, CACNG2, and OPRM1) were genotyped. Logistic regression analyses were performed.

Results

Three hundred and forty‐five patients were available for the genetic analyses. The prevalence of CPSP 3 months post‐operatively was 10.5% and after 12 months 7.9%. The polymorphism rs4818 within the COMT gene was associated with the prevalence of CPSP after 3 months. No polymorphisms were associated with CPSP after 12 months. The addition of rs4818 to the prediction model did not change its discriminatory power significantly.

Conclusion

The rs4818 polymorphism within the COMT gene was associated with the prevalence of CPSP 3 months after hysterectomy, but the implementation of rs4818 into the prediction model did not significantly improve the chance of identifying hysterectomy patients at risk for CPSP.
Hot Off the Press: SGEM #257—EMTALA: It's the Law of the Land
Authors: Heitz Corey , Morgenstern Justin , Bond Christopher , Milne William K.
Published: June 2019

The Office of the Inspector General has the authority to levy fines relating to violations of the Emergency Medicine Treatment and Labor Act (EMTALA) for both medical and psychiatric care. Terp et al. have described the incidence of violations and penalties levied for psychiatric cases and compared them to that for medical. This article reviews that article and the podcast recorded with Dr. Terp and the ensuing discussion in the podcast and online.
A comparison of uterine natural killer cell density in the peri‐implantation period between natural cycles and hormone replacement therapy cycles
Authors: Yang Wen‐Jui , Chen Xiaoyan , Zhao Yiwei , Cheung Wing Ching , Hsiao Shun‐Yu , Liu Yingyu , Law Tracy Sze Man , Chung Jacqueline Pui Wah , Li Tin Chiu
Published: June 2019

Problem

A reference range for uterine natural killer (uNK) cell density in the peri‐implantation period has recently been established in natural cycles. However, it is uncertain whether the results can be applied to hormonal replacement therapy (HRT) cycles, used increasingly in frozen‐thaw embryo replacement cycles and which is known to be capable of supporting implantation.

Method of Study

A total of 183 women from two IVF centers participated in this study, including 75 women in natural cycles and 108 women in HRT cycles. All endometrial biopsies were collected precisely on the putative day of embryo implantation, namely 7 days after LH surge (LH+7) of the natural cycles or 5 days after initiation of progesterone (P+5) of the HRT cycles. Endometrial sections were immunostained for CD56 for uNK cells. Cell counting was performed by a standardized protocol, and results were expressed as percentage of positive uNK cells/total stromal cells.

Results

There was no significant difference (P > 0.05) in uNK cell density between natural cycles (median 2.28%, range 0.99%‐4.78%) and HRT cycles (median 2.55%, range 0.69%‐5.02%) in women undergoing IVF‐ET treatment on the putative day of blastocyst transfer. Using reference range from 1.2% to 4.5% for uNK cell density, there was no significant difference (P > 0.05) in high uNK cell density proportion between natural cycles (8%, 6/75) and HRT cycles (10.2%, 11/108).

Conclusion

The results indicated that the reference range for uNK cell density derived from natural cycles may apply to HRT cycles.
Single‐cell technologies in reproductive immunology
Authors: Vazquez Jessica , Ong Irene M. , Stanic Aleksandar K.
Published: June 2019

The maternal‐fetal interface represents a unique immune privileged site that maintains the ability to defend against pathogens while orchestrating the necessary tissue remodeling required for placentation. The recent discovery of novel cellular families (innate lymphoid cells, tissue‐resident NK cells) suggests that our understanding of the decidual immunome is incomplete. To understand this complex milieu, new technological developments allow reproductive immunologists to collect increasingly complex data at a cellular resolution. Polychromatic flow cytometry allows for greater resolution in the identification of novel cell types by surface and intracellular protein. Single‐cell RNA‐seq coupled with microfluidics allows for efficient cellular transcriptomics. The extreme dimensionality and size of data sets generated, however, requires the application of novel computational approaches for unbiased analysis. There are now multiple dimensionality reduction (tSNE, SPADE) and visualization tools (SPICE) that allow researchers to efficiently analyze flow cytometry data. Development of computational tools has also been extended to RNA‐seq data (including scRNA‐seq), which requires specific analytical tools. Here, we provide an overview and a brief primer for the reproductive immunology community on data acquisition and computational tools for the analysis of complex flow cytometry and RNA‐seq data.
Visual cognitive impairments in children at risk of prenatal alcohol exposure
Authors: Castillo Castejón Olimpia , González Inmaculada , Prieto Esther , Pérez Teresa , Pablo Luis E. , Pueyo Victoria
Published: June 2019

Aim

To evaluate the relationship between visoperception and anthropometric features related to prenatal alcohol exposure.

Methods

We compared two cohorts of infants aged between 5 and 18 years. Seventy‐nine children, adopted from Eastern Europe, were included in the study group. The control group was formed by age and gender matched children born in Spain. All children underwent a full ophthalmologic assessment and standardised testing of visual cognitive skills.

Results

Adoptees presented worse visual motor and visual perceptual outcomes in all skills compared with control subjects, with statistically significant difference in test of visual perceptual skills (TVPS) global centile (50.3 vs 66.8; P = 0.001), spatial relationships (64.6 vs 81.9; P = 0.004) and visual figure–ground (52.1 vs 74.1; P = 0.002) tasks. Face recognition was as well significantly worse in adopted children (42.4 vs 57.1; P = 0.009). Twenty‐one adopted children (26.6%) had sentinel finding for foetal alcohol spectrum disorders (FASD). Main facial features related to FASD correlated with visual cognitive outcomes. Of the adopted children, those diagnosed of FASD showed incrementally worse visual perceptual and visual motor outcomes (TVPS global centile = 36.86, P = 0.001; TVAS = 10.38, P = 0.002).

Conclusion

Children adopted from eastern Europe are at increased risk of visual perceptual disabilities, especially those with sentinel findings of foetal alcohol syndrome disorders.
Rapid face processing for positive and negative emotions in 5‐, 7‐, and 12‐month‐old infants: An exploratory study
Authors: Miguel Helga O. , McCormick Sarah A. , Westerlund Alissa , Nelson Charles A.
Published: June 2019

Processing of positive and negative facial expressions in infancy follows a distinct course with a bias towards fearful facial expressions starting at 7 months of age; however, little is known about the developmental trajectory of fear processing and other facial expressions, and if this bias is driven by specific regions of the face. This study used eye tracking to examine the processing of positive and negative emotional faces in independent groups of 5‐ (n = 43), 7‐ (n = 60), and 12‐month‐old infants (n = 70). Methods: Infants were shown static images of female faces exhibiting happy, anger, and fear expressions, for one‐second each. Total looking time and looking time for areas of interest (AOIs) including forehead and eyes (top), mouth and chin (bottom), and contour of each image were computed. Infants across all ages looked longer to fear faces than angry or happy faces. Negative emotions generally elicited greater looking times for the top of the face than did happy faces. In addition, we also found that at 12 months of age infants looked longer for the bottom of the faces than did 5‐month‐olds. Our study suggests that the visual bias to attend longer to fearful faces may be in place by 5 months of age, and between 5 and 12 months of age, there seems to be a developmental shift towards looking more to the bottom of the faces.

Statement of contribution

What is already known in this subject?

Bias for fear face processing is present at 7 months of age.

Using older data collection systems, we have some idea about which facial features recruit infant attention.

What the present study adds?

Well‐controlled paradigm that examines both positive and negative facial expressions, to different areas of interest in the face.

Use of the same paradigm to test a cross‐sectional sample of infants in distinct developmental stages – 5, 7, and 12 months.
‘Dr Google’: trends in online interest in prostate cancer screening, diagnosis and treatment
Authors: Rezaee Michael E. , Goddard Briana , Sverrisson Einar F. , Seigne John D. , Dagrosa Lawrence M.
Published: June 2019

Objectives

To examine trends in online search behaviours related to prostate cancer on a national and regional scale using a dominant major search engine.

Materials and Methods

Google Trends was queried using the terms ‘prostate cancer’, ‘prostate‐specific antigen’ (PSA), and ‘prostate biopsy’ between January 2004 and January 2019. Search volume index (SVI), a measure of relative search volume on Google, was obtained for all terms and examined by region and time period: pre‐US Preventive Services Task Force (USPSTF) Grade D draft recommendation on PSA screening; during the active Grade D recommendation; and after publication of the recent Grade C draft recommendation.

Results

Online interest in PSA screening differed by time period (P < 0.01). The SVI for PSA screening was greater pre‐Grade D draft recommendation (82.7) compared to during the recommendation (74.5), while the SVI for PSA screening was higher post‐Grade C draft recommendation (90.4) compared to both prior time periods. Similar results were observed for prostate biopsy and prostate cancer searches. At the US state level, online interest in prostate cancer was highest in South Carolina (SVI 100) and lowest in Hawaii (SVI 64). For prostate cancer treatment options, online interest in cryotherapy, prostatectomy and prostate cancer surgery overall increased, while searches for active surveillance, external beam radiation, brachytherapy and high‐intensity focused ultrasonography remained stable.

Conclusion

Online interest in prostate cancer has changed over time, particularly in accordance with USPSTF screening guidelines. Google Trends may be a useful tool in tracking public interest in prostate cancer screening, diagnosis, and treatment, especially as it relates to major shifts in practice guidelines.
Back to the basics: Rethinking partial correlation network methodology
Authors: Williams Donald R. , Rast Philippe
Published: June 2019

The Gaussian graphical model (GGM) is an increasingly popular technique used in psychology to characterize relationships among observed variables. These relationships are represented as elements in the precision matrix. Standardizing the precision matrix and reversing the sign yields corresponding partial correlations that imply pairwise dependencies in which the effects of all other variables have been controlled for. The graphical lasso (glasso) has emerged as the default estimation method, which uses ℓ1‐based regularization. The glasso was developed and optimized for high‐dimensional settings where the number of variables (p) exceeds the number of observations (n), which is uncommon in psychological applications. Here we propose to go ‘back to the basics’, wherein the precision matrix is first estimated with non‐regularized maximum likelihood and then FisherZtransformed confidence intervals are used to determine non‐zero relationships. We first show the exact correspondence between the confidence level and specificity, which is due to 1 minus specificity denoting the false positive rate (i.e., α). With simulations in low‐dimensional settings (p ≪ n), we then demonstrate superior performance compared to the glasso for detecting the non‐zero effects. Further, our results indicate that the glasso is inconsistent for the purpose of model selection and does not control the false discovery rate, whereas the proposed method converges on the true model and directly controls error rates. We end by discussing implications for estimating GGMs in psychology.
Post‐Last Glacial Maximum glacier fluctuations in the southern Écrins massif (westernmost Alps): insights from 10Be cosmic ray exposure dating
Authors: Hofmann Felix Martin , Alexanderson Helena , Schoeneich Philippe , Mertes Jordan R. , Léanni Laëtitia ,   Aster Team (Georges Aumaître, Didier L. Bourlès, Karim Keddadouche)
Published: June 2019

Only a few chronological constraints on Lateglacial and Early Holocene glacier variability in the westernmost Alps have hitherto been obtained. In this paper, moraines of two palaeoglaciers in the southern Écrins massif were mapped. The chronology of the stabilization of selected moraines was established through the use of 10Be cosmic ray exposure (CRE) dating. The equilibrium line altitude (ELA) during moraine deposition was reconstructed assuming an accumulation area ratio (AAR) of 0.67. Ten pre‐Little Ice Age (LIA) ice‐marginal positions of the Rougnoux palaeoglacier were identified and seven of these have been dated. The 10Be CRE age of a boulder on the lowermost sampled moraine indicates that the landform may have been first formed during a period of stable glaciers at around 16.2±1.7 ka (kiloyears before AD 2017) or that the sampled boulder experienced pre‐exposure to secondary cosmic radiation. The moraine was re‐occupied or, alternatively, shaped somewhat before 12.2±0.6 ka when the ELA was lowered by 230 m relative to the LIA ELA. At least six periods of stable ice margins occurred thereafter when the ELA was 220–160 m lower than during the LIA. The innermost dated moraine stabilized at or before 10.9±0.7 ka. Three 10Be CRE ages from a moraine of the Prelles palaeoglacier indicate a period of stationary ice margins at or before 10.9±0.6 ka when the ELA was lowered by 160 m with respect to the end of the LIA. The presented 10Be CRE ages are in good agreement with those of moraines that have been attributed to the Egesen stadial. Assuming unchanged precipitation, summer temperature in the southern Écrins massif at ~12 ka must have been at least 2 °C lower relative to the LIA.
Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series
Authors: Kubo Terufumi , Tsurita Giichiro , Hirohashi Yoshihiko , Yasui Hiroshi , Ota Yasunori , Watanabe Kazue , Murai Aiko , Matsuo Kazuhiko , Asanuma Hiroko , Shima Hiroaki , Wada Satoshi , Nakatsugawa Munehide , Kanaseki Takayuki , Tsukahara Tomohide , Mizuguchi Toru , Hirata Koichi , Takemasa Ichiro , Imai Kohzoh , Sato Noriyuki , Torigoe Toshihiko
Published: June 2019

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer by providing new options in addition to existing therapies. However, peptide vaccination therapies still represent an attractive approach, because of the antigen specificity. We identified survivin 2B peptide (SVN‐2B), a 9‐mer antigenic peptide encoded by survivin, and an SVN‐2B peptide vaccine‐based phase II randomized clinical trial targeting unresectable and refractory pancreatic carcinoma was undertaken. The SVN‐2B peptide vaccine did not have any statistically significant clinical benefits in that study. Therefore, we undertook an autopsy study to analyze the immune status of the pancreatic cancer lesions at the histological level. Autopsies were carried out in 13 patients who had died of pancreatic cancer, including 7 who had received SVN‐2B peptide vaccination and 6 who had not, as negative controls. The expression of immune‐related molecules was analyzed by immunohistochemical staining. Cytotoxic T lymphocytes were analyzed by tetramer staining and enzyme‐linked immunospot assay. Histological analysis revealed dense infiltration of CD8+ T cells in some lesions in patients who had received the SVN‐2B peptide vaccine. A high rate of programmed cell death ligand 1 expression in cancer cells was observed in these cases, indicating that CTLs were induced by SVN‐2B peptide vaccination and had infiltrated the lesions. The lack of a significant antitumor effect was most likely attributable to the expression of immune checkpoint molecules. These findings suggest that the combination of a tumor‐specific peptide vaccine and an ICI might be a promising approach to the treatment of pancreatic carcinoma in the future.
Can Healthier Contexts Be Harmful? A New Perspective on the Plight of Victims of Bullying
Authors: Garandeau Claire F. , Salmivalli Christina
Published: June 2019

With rising awareness of the negative effects of school bullying on victims’ psychosocial adjustment, schools worldwide are intervening more to try to reduce bullying among their students. However, even when these interventions succeed (i.e., lead to average decreases in bullying), some children continue to experience victimization. Recent studies suggest that their situation is particularly concerning: The adjustment difficulties commonly experienced by victims of bullying may be exacerbated in social contexts in which less victimization occurs, the proportion of victims has decreased, or an antibullying program is being implemented. The possibility that improved social contexts harm some individuals has been referred to as the healthy context paradox. Although strict evidence of this paradox is pending, in this article, we discuss plausible explanations for it, such as causal attributions for the bullying and opportunities for friendship, as well as possible implications for antibullying interventions.
Early Years Parenting Mediates Early Adversity Effects on Problem Behaviors in Intellectual Disability
Authors: Totsika Vasiliki , Hastings Richard P. , Emerson Eric , Hatton Chris
Published: June 2019

A family developmental framework was applied to data from families of children with intellectual disabilities to understand the role of parenting in the path from early adversity to problem behaviors in mid‐childhood. Data from 9 months to 11 years tested the Family Stress Model in families of 555 children. Adversarial parenting between 3 and 5 years mediated the path from early adversity (family poverty and maternal psychological distress at nine months) to problem behaviors at 7 and 11 years. Positive parent–child relationship only mediated the path to conduct problems. Multiple mediation was not present. Early adversity impacts both positive parent–child relationship and adversarial parenting between three and five, but the latter is crucial for problem behaviors in mid‐childhood.
TNF-derived peptides inhibit tumour growth and metastasis through cytolytic effects on tumour lymphatics
Authors: Lu W , Wang Y , Zhang Q , Owen S , Green M , Ni T , Edwards M , Li Y , Zhang L , Harris A , Li J-L , Jackson D G , Jiang S
Published: June 2019

Tumour necrosis factor (TNF) is a multi-functional cytokine with profound and diverse effects on physiology and pathology. Identifying the molecular determinants underlying the functions and pathogenic effects of TNF is key to understanding its mechanisms of action and identifying new therapeutic opportunities based on this important molecule. Previously, we showed that some evolutionarily conserved peptides derived from TNF could induce cell death (e.g. apoptosis and/or necrosis), a feature of immune defence mechanisms shared by many vertebrates. In this study, we demonstrated that necrosis-inducing peptide P16 kills human glioblastoma cancer cells and primary human hepatoma or renal cancer cells isolated from patients who had not responded to standard treatments. Importantly, we show that the necrosis-inducing peptide P1516 significantly improves survival by inhibiting tumour metastasis in a 4T1 breast cancer syngeneic graft mouse model. Because the lymphatic system is an important metastatic route in many cancers, we also tested the effect of TNF-derived peptides on monolayers of primary human lymphatic endothelial cells (hDLEC) and found that they increased junctional permeability by inducing cytoskeletal reorganization, gap junction formation and cell death. Transmission electron microscopy imaging evidence, structural analysis and in-vitro liposome leakage experiments strongly suggest that this killing is due to the cytolytic nature of these peptides. P1516 provides another example of a pro-cytotoxic TNF peptide that probably functions as a cryptic necrotic factor released by TNF degradation. Its ability to inhibit tumour metastasis and improve survival may form the basis of a novel approach to cancer therapy.
Implant failures and age at the time of surgery: A retrospective study on implant treatment in 2915 partially edentulous jaws
Authors: Jemt Torsten
Published: June 2019

Purpose

To further report and analyze data on the prevalence of implant failures related to age at surgery in partially edentulous jaws.

Materials and Methods

Altogether, 2915 partially edentulous jaws (Kennedy Class I and II) were consecutively treated with 9167 implants over a 30‐year period (1986‐2015) in one referral clinic. All implant failures were consecutively recorded and the first event of implant failure was analyzed in relation to patient age at implant surgery.

Results

A total of 2453 patients participated in the study. The main observations were a nonlinear, normal distribution association between risk of implant failure and age at surgery with the highest risk in middle‐aged patients. The risk for implant failures was significantly higher for middle‐aged patients (45‐64 years) than for old patients at the time of surgery (P < .05). The overall cumulative survival rates for treated jaws increased consistently from the age group of 40 to 49 years to that of >79 years. However, younger age groups (<40 years) presented a different pattern. Partially edentulous patients included late in the study (2003‐2015) presented a more pronounced nonlinear, normal distribution, and the highest risk of implant failure in patients between 50 and 55 years of age at surgery.

Conclusions

An overall nonlinear risk pattern of implant failure was observed, with the highest risk in the middle‐aged group at implant surgery. Overall cumulative survival rates were highest in the youngest and oldest age groups at implant surgery, and this pattern became more pronounced in patients included late in the study.
Deconstructing compassionate conservation
Authors: Hayward Matt W. , Callen Alex , Allen Benjamin L. , Ballard Guy , Broekhuis Femke , Bugir Cassandra , Clarke Rohan H. , Clulow John , Clulow Simon , Daltry Jennifer C. , Davies‐Mostert Harriet T. , Fleming Peter J. S. , Griffin Andrea S. , Howell Lachlan G. , Kerley Graham I. H. , Klop‐Toker Kaya , Legge Sarah , Major Tom , Meyer Ninon , Montgomery Robert A. , Moseby Katherine , Parker Daniel M. , Périquet Stéphanie , Read John , Scanlon Robert J. , Seeto Rebecca , Shuttleworth Craig , Somers Michael J. , Tamessar Cottrell T. , Tuft Katherine , Upton Rose , Valenzuela‐Molina Marcia , Wayne Adrian , Witt Ryan R. , Wüster Wolfgang
Published: June 2019

Compassionate conservation focuses on 4 tenets: first, do no harm; individuals matter; inclusivity of individual animals; and peaceful coexistence between humans and animals. Recently, compassionate conservation has been promoted as an alternative to conventional conservation philosophy. We believe examples presented by compassionate conservationists are deliberately or arbitrarily chosen to focus on mammals; inherently not compassionate; and offer ineffective conservation solutions. Compassionate conservation arbitrarily focuses on charismatic species, notably large predators and megaherbivores. The philosophy is not compassionate when it leaves invasive predators in the environment to cause harm to vastly more individuals of native species or uses the fear of harm by apex predators to terrorize mesopredators. Hindering the control of exotic species (megafauna, predators) in situ will not improve the conservation condition of the majority of biodiversity. The positions taken by so‐called compassionate conservationists on particular species and on conservation actions could be extended to hinder other forms of conservation, including translocations, conservation fencing, and fertility control. Animal welfare is incredibly important to conservation, but ironically compassionate conservation does not offer the best welfare outcomes to animals and is often ineffective in achieving conservation goals. Consequently, compassionate conservation may threaten public and governmental support for conservation because of the limited understanding of conservation problems by the general public.
Transanal endoscopic microsurgery for rectal lesions in a specialist regional early rectal cancer centre: the Mersey experience
Authors: Ondhia M. , Tamvakeras P. , O'Toole P. , Montazerri A. , Andrews T. , Farrell C. , Ahmed S. , Slawik S. , Ahmed S. ,   the Merseyside Early Rectal Cancer Network
Published: June 2019

Aim

Organ‐preserving local excision by transanal endoscopic microsurgery (TEM) for early rectal cancer offers significantly lower morbidity as compared to formal rectal cancer resection with acceptable outcomes. This study presents our 6‐year experience of TEM for rectal lesions referred to a specialist early rectal cancer centre in the UK.

Method

Data were collected for all patients referred for TEM of suspected early rectal cancer to a regional specialist early rectal cancer multidisciplinary team (MDT) over a 6‐year period.

Results

One hundred and forty‐one patients who underwent full‐thickness TEM for suspected or confirmed early rectal cancer were included. Thirty patients were referred for TEM following incomplete endoscopic polypectomy. Final pathology was benign in 77 (54.6%) cases and malignant in 64 (45.4%). Of the 61 confirmed adenocarcinomas, TEM resections were pT0 in 17 (27.9%), pT1 in 32 (51.7%), pT2 in 11 (18.0%) and pT3 in 1 (1.6%). Thirty‐eight of 61 patients (62.3%) had one or more poor histological prognostic features and these patients were offered further treatment. Twenty‐three of 61 (37.7%) patients with rectal adenocarcinoma required no further treatment following TEM. Forty‐three cases of rectal adenocarcinoma were available for establishing recurrence rates. Two of 43 patients (4.7%) developed a recurrence at a median follow‐up of 28.7 months (12.1–66.5 months). The overall estimated 5‐year overall survival rate was 87.9% and the disease‐free survival rate was 82.9%.

Conclusion

Acceptable outcomes are possible for TEM surgery with appropriate patient selection, effective technique, expert histopathology, appropriate referral for adjuvant treatment and meticulous follow‐up. This can be achieved through an early rectal cancer MDT in a dedicated specialist regional centre.
Diagnostic yield of broncho‐alveolar lavage for pembrolizumab induced sarcoid‐like reaction of the lung
Authors: Grosse Alexandra , Grosse Claudia
Published: June 2019

Immune checkpoint inhibitors may cause sarcoid‐like reaction of the lung. Broncho‐alveolar lavage demonstrates lymphocytosis in this setting; the CD4+/CD8+ ratio was not increased in the current case. This pattern is similar, but not identical to sarcoidosis. Drug‐induced pneumonitis, tumour recurrence or pneumonia, the main differential diagnoses for sarcoid‐like reaction, can reliably be distinguished using broncho‐alveolar lavage.
Visual Function Classification System for children with cerebral palsy: development of a new tool
Authors: Rosenbaum Peter
Published: June 2019

This commentary is on the original article by Baranello et al. on pages 104‐110 of this issue
Exploring the perceptions of emotional distress among couples living with Type 2 diabetes and among diabetes healthcare providers, and consideration of support needs
Authors: Berry E. , Davies M. , Dempster M.
Published: June 2019

Aims

To compare the emotional distress experienced by people with Type 2 diabetes with the perceptions of their partners, and to explore the perceptions of healthcare providers and how these differ from the perceptions and experiences of couples living with Type 2 diabetes regarding their support needs.

Methods

A purposive sample of people with Type 2 diabetes and their partners was recruited through Diabetes UK media outlets and support groups, while healthcare providers were recruited through hospital and diabetes education teams. Inductive thematic analysis was conducted.

Results

Seven people with Type 2 diabetes and six partners took part in separate semi‐structured interviews and seven healthcare providers took part in focus groups. Themes emerged regarding unique psychological struggles for people with Type 2 diabetes: ‘sense of restriction’; ‘disempowerment’; and ‘acceptance of diabetes’. For partners the themes of ‘feeling responsible’ and ‘need for greater involvement’ emerged. Common themes arising from people with Type 2 diabetes, partners and healthcare providers highlighted diabetes‐related stresses: ‘self‐care struggles’ and ‘perceived need for appropriate psychological support’. A key theme drawn from healthcare providers was ‘perceived professional barriers to psychological support’, which captures concerns related to providing emotional support in clinical practice.

Conclusions

People with Type 2 diabetes, partners, and healthcare providers share a common understanding of the emotional stresses of living with Type 2 diabetes, but also experience diabetes differently depending on their role and responsibilities. All face barriers that need to be considered to ensure that emotional support in diabetes is meaningful and feasible in routine practice.
The economics of the Books of Moses
Authors: Koehler Benedikt
Published: June 2019

The Books of Moses contained economic precepts that made a twofold impact in the history of economic thought. First, Mosaic precepts shaped Israel's transition from a nomadic to a sedentary economy. This transition as such had parallels in many other societies, but Israel's case was unique in that Moses grounded economic precepts on theology. Second, Moses shaped conceptions of economics by Jews and by non‐Jews, in two ways: first, he laid a path for theologically derived economics that continued in Christianity and in Islam; second, he cast terms of reference for the right to own property that were dominant in Western economic thinking until the Enlightenment.
‘Market failure’ arguments are a poor guide to policy
Authors: Bourne Ryan
Published: June 2019

‘Market failure’ is frequently offered as a justification for government intervention in the economy. Proponents of interventions can point to almost limitless examples of markets which do not meet all the criteria for Pareto optimality and argue that government taxation, subsidies or regulation can perfect them, maximising social welfare. But comparing market outcomes with an unattainable and unidentifiable ideal is not useful in a world of imperfect knowledge and government failure. It is better to compare market outcomes against realistic alternatives. Furthermore, even within the market failure paradigm, concepts such as ‘public goods’ and ‘negative externalities’ are routinely misunderstood and inconsistently applied. This leads to predictably poor policy outcomes.
Why comparative advantage is a problematic guide to practical policy
Authors: Xie Sherman
Published: June 2019

Previous criticisms of comparative advantage theory have mainly stressed the inapplicability of its theoretical assumptions. This article focuses on the dilemma involved in using it as a guide to practical policy. Since its inception, comparative advantage theory has gradually split into two schools, representing two ways of thinking and two methodologies. Economic policy based on comparative advantage may succeed in the short run but fail in the long run, because the development model based on this approach has an inherent destructive mechanism.
The Internet's impact on trademark applications
Authors: Gnangnon Sena Kimm
Published: June 2019

This article assesses empirically the impact of Internet access on the number of trademark applications submitted by countries' residents. The analysis suggests that promotion of access to the Internet influences positively the submission of trademark applications by residents. Greater access to the Internet exerts a stronger positive effect on trademark submissions in developed countries than in developing ones. This positive effect is enhanced when countries further liberalise their trade regimes.
Hemorrhage and associated fistula formation in a left atrial myxoma causing coronary artery steal syndrome
Authors: Su Yongwei , Song Haibo
Published: June 2019

A 59‐year‐old woman with episodes of chest pain was diagnosed with cardiac myxoma. Transesophageal echocardiography (TEE) showed a massive vascularized tumor and there was a blood stream spurting from the internal cavity of tumor into left atrium through an interconnected sinus tract. Coronary artery angiography (CAG) indicated that the mass was enhanced upon the administration of contrast media, which spouted into the cardiac chamber. This is the first case to report the development of the coronary artery steal syndrome due to hemorrhage and associated fistula formation in a left atrial myxoma, which was detected by TEE and confirmed by CAG.