bluuebunny/crossref_metadata_2025 huggingface dataset:
Grave‐goods from the long chamber tomb “Dibba 76/1” (Fujairah, UAE): a first inventory
Authors: Pellegrino Maria Paola , Esposti Michele Degli , Buta Marilisa , Tagliamonte Enrica , Hassan Salah Ali
Published: January 2019

The aim of this paper is to present the rich set of finds collected inside the grave Dibba 76/1, in the Emirate of Fujairah, during a season of rescue excavation conducted under the direction of S. Ali Hassan in 1994. The recovered grave‐goods include pottery, soft‐stone vessels, metal finds, personal ornaments, coins, and other items. Although comparable with other corpuses of material excavated in south‐eastern Arabia, the material of Dibba 76/1 stands out for the inner variety of the different artefacts’ classes and their remarkable chronological heterogeneity. The study of the grave‐goods suggests that Dibba 76/1 was reused over several centuries, showing a strong continuity in the funerary destination of this specific place from the end of the Wadi Suq period (2000–1600 BC) to the first phases of the late pre‐Islamic period (250 BC–AD 400), and the full integration of the area of Dibba in the succession of the various cultural facies known during this long time span.
Continuation of Gender Disparities in Pay Among Academic Emergency Medicine Physicians
Authors: Wiler Jennifer L. , Rounds Kirsten , McGowan Becky , Baird Janette
Published: January 2019

Objectives

The objective was to identify the effects of gender and other predictors of change in the salary of academic emergency physicians over a four sequential time period of survey administration, across a sample of physicians within different emergency departments (EDs) and within states representing the four main geographical regions of the United States.

Methods

This was a successive cross‐sectional observational study of EDs in the United States using an annual salary survey distributed to all Association of Academic Chairs in Emergency Medicine (AACEM) and Academy of Administrators in Academic Emergency Medicine (AAAEM) members in 2013, 2015, 2016, and 2017 with a sample size of 7,102 respondents over all time periods. The primary variable of interest was the adjusted base salary, calculated to be the full‐time effort of the physician without any enhancements (e.g., without stipend, release time, extra hours). Institutional predictive variables included U.S. region that ED was in and if the site was an academic or community academic hybrid (“community”) ED. Individual level variables included gender, academic rank, years at academic rank, years at rank within the ED, and primary duty (clinical or other). A series of Wilcoxon tests were conducted to determine if the unadjusted difference in salaries by gender for each year of the survey were significantly different. The effects of relative change in adjusted base salary over time were assessed using a mixed‐effects regression model, with institutional‐ and individual‐level predictors included in the model.

Results

Data were provided by 81 departments across the four geographic regions of the United States (Northeast, South, West, and Midwest). Most of the survey respondents across the four time periods of administration were male (65%) and reported primary clinical appointments at an academic ED (94%). Overall salaries increased across the four time points of the data with an overall relative 10.8% (95% confidence interval [CI] = 9.6%–12%) change in median salary between 2013 and 2017; the relative percentage change for female respondents was 10.6% (95% CI = 9.4%–11.85%) and 11.1% (95% CI = 10.2%–12%) for males. Within survey years, not adjusting for academic rank, the median salary increase for males was higher ($226,746 in 2013 to $252,000 in 2017) than females ($217,000 in 2013 to $240,000 in 2017), with significance at all four time points (Z = 6.33, p < 0.001), with a median average salary gap of $12,000 in 2017. In the predictive model that adjusted for covariates, gender significantly predicted median adjusted salary, with males earning significantly more than females (F(1) = 22.5, p < 0.001).

Conclusions

Despite previously published data showing an inappropriate gender salary gap in emergency medicine, this gap has remained essentially unchanged over the past 4 years.
Causes of stillbirths in diabetic and gestational diabetes pregnancies at a NSW tertiary referral hospital
Authors: Wang Mawson , Athayde Neil , Padmanabhan Suja , Cheung Ngai Wah
Published: January 2019

Background

Diabetes in pregnancy may result in stillbirth or neonatal death.

Aim

This audit examined stillbirths of mothers with pre‐existing diabetes in pregnancy (DIP) and gestational diabetes (GDM) to determine maternal and diabetic characteristics implicated in these deaths.

Materials and Methods

A retrospective cohort study was conducted to identify stillbirths occurring in diabetic pregnancies at Westmead Hospital during 2006–2017. Medical records were reviewed to obtain data relating to maternal factors, diabetes history, glycaemic control and cause of death.

Results

There were 37 women (seven with type 1 diabetes [T1DM], 11 with type 2 diabetes [T2DM] and 19 with GDM) who had 38 stillbirths. The leading cause of stillbirth was lethal congenital malformations in nine cases, followed by placental and umbilical abnormalities in six, intra‐uterine growth restriction (IUGR) in six, and obstetric factors in four cases. Malformations were predominantly cardiovascular (n = 7), musculoskeletal (n = 5) and gastrointestinal (n = 4). There was no difference in the proportion of stillbirths related to malformations between the DIP and GDM groups (P = 0.22). In the pre‐conception period or first trimester, all T1DM subjects and all but two T2DM subjects had HbA1c >7% or there was no measurement. HbA1c was >7% in 6/7 T1DM subjects and 7/11 T2DM subjects at some stage during the pregnancy.

Conclusion

Stillbirth remains a problem in diabetic pregnancy in the 21st century. Lethal malformations, placental abnormalities and IUGR were the leading causes of stillbirth related to diabetes. Pre‐conception counselling and planning to achieve better glycaemic control in pregnancy needs to be improved.
Maternal mortality and ‘near miss’ morbidity at a tertiary hospital in Timor‐Leste
Authors: Jayaratnam Skandarupan , Soares Maria Lucia de Fatima Godinho , Jennings Belinda , Thapa Amitha Pradan , Woods Cindy
Published: January 2019

Background

Assessment of severe maternal morbidity is increasingly being undertaken to understand the aetiology and factors which lead to adverse maternal outcomes. Their use in conjunction with maternal deaths may allow a comprehensive assessment of care provided, highlight areas for improvement within the health system and allow benchmarking of care against other institutions. Timor‐Leste has one of the highest rates of maternal mortality in the Asia‐Pacific region; however, there has been limited research into the level of severe obstetric morbidity in the country.

Aim

To determine the aetiology and rates of severe obstetric morbidity and mortality at Hospital Nacional Guido Valadares, Timor‐Leste.

Methods and Materials

Cases of maternal ‘near misses’ and deaths were prospectively identified over a period of 12 months using the World Health Organization maternal near‐miss criteria. Cases of maternal death and near miss were combined (severe maternal outcomes) for descriptive analysis.

Results

During the audit period, 69 severe maternal outcomes were identified: 30 maternal deaths and 39 ‘near misses’. The maternal mortality ratio and the maternal near‐miss ratio were 662/100 000 live births and 8/1000 live births, respectively. The main identified obstetric aetiologies were haemorrhage and pre‐eclampsia, while 22% of severe maternal outcomes did not have a clearly identified cause.

Conclusion

The high institutional maternal mortality ratio requires urgent attention and identification of areas for improvement. Auditing and benchmarking using the WHO near‐miss criteria provide a mechanism for standardised comparison of obstetric care but require further refinement to the local context.
High‐flow nasal oxygen vs. standard flow‐rate facemask pre‐oxygenation in pregnant patients: a randomised physiological study
Authors: Shippam W. , Preston R. , Douglas J. , Taylor J. , Albert A. , Chau A.
Published: January 2019

High‐flow nasal oxygen has been shown to provide effective pre‐oxygenation and prolong apnoeic time during intubation attempts in non‐pregnant patients. We aimed to compare pre‐oxygenation using high‐flow nasal oxygen (30–70 l.min−1 oxygen flow) via nasal prongs with standard 15 l.min−1 oxygen breathing via a tight‐fitting facemask. Forty healthy parturients were randomly allocated to these two groups, and furthermore each patient underwent the selected pre‐oxygenation method with both 3‐min tidal volume breathing and 30s tidal breathing followed by eight vital capacity breaths. With 3‐min tidal volume breathing, the respective estimated marginal means for high‐flow nasal oxygen and standard flow rate facemask pre‐oxygenation were 87.4% (95%CI 85.5–89.2%) and 91.0% (95%CI 89.3–92.7%), p = 0.02; with eight vital capacity breaths the estimated marginal means were 85.9% (95%CI 84.1–87.7%) and 91.8% (95%CI 90.1–93.4%, p < 0.0001). Furthermore, high‐flow nasal oxygen did not reliably achieve a mean end‐tidal oxygen concentration ≥ 90% compared with the standard flow rate facemask. In this physiological study, high‐flow nasal oxygen pre‐oxygenation performed worse than standard flow rate facemask pre‐oxygenation in healthy term parturients.
A comparison of sufentanil vs. remifentanil in fast‐track cardiac surgery patients
Authors: Zakhary W. Z. A. , Turton E. W. , Flo Forner A. , von Aspern K. , Borger M. A. , Ender J. K.
Published: January 2019

We retrospectively compared patients receiving remifentanil with patients receiving sufentanil undergoing fast‐track cardiac surgery. After 1:1 propensity score matching there were 609 patients in each group. The sufentanil group had a significantly longer mean (SD) ventilation time compared with the remifentanil group; 122 (59) vs. 80 (44) min, p < 0.001 and longer mean (SD) length of stay in the recovery area; 277 (77) vs. 263 (78) min, p = 0.002. The sufentanil group had a lower mean (SD) visual analogue pain score than the remifentanil group; 1.5 (1.2) vs. 2.4 (1.5), p < 0.001 and consumed less mean (SD) piritramide (an opioid analgesic used in our hospital); 2.6 (4.7) vs. 18.9 (7.3) mg, p < 0.001. The results of our study show that although remifentanil was more effective in reducing time to tracheal extubation and length of stay in the recovery area, there was an increased requirement for postoperative analgesia when remifentanil was used.
Human sperm DNA damage has an effect on immunological interaction between spermatozoa and fallopian tube
Authors: Zandieh Z. , Ashrafi M. , Aflatoonian K. , Aflatoonian R.
Published: January 2019

Background

Toll‐like receptors play a crucial role in the immunological interaction between the spermatozoa and fallopian tube and contribute to the ovulation, sperm capacitation, fertilization, and pregnancy.

Objectives

To investigate the expression of toll‐like receptors and their adaptor molecules and cytokines under the effect of spermatozoa with high DNA fragmentation (high DF) in human fallopian tube cell line (OE‐E6/E7) and compare to those in normal spermatozoa.

Materials and methods

Fresh semen samples were obtained from 10 unexplained infertile males with high DF (more than 20%) and from 10 healthy donors with a DF less than 3%. After sperm preparation, samples were co‐cultured with OE‐E6/E7. Toll‐like receptors, myeloid differentiation factor 88 (MyD88), TIR domain‐containing adapter protein (TIRAP), TIR domain‐containing adapter‐inducing IFN‐b (TRIF), TRIF‐related adapter molecule as well as IL‐6, IL‐8, IFN‐β, and TNFα mRNA expression were evaluated by quantitative real‐time PCR. Protein levels of these cytokines and chemokines were measured using ELISA method.

Results

TLR 1‐6 mRNA expression in OE‐E6/E7 was significantly higher under the effect of spermatozoa with high DF compared to the spermatozoa with low DF. Furthermore, significantly increased mRNA expression of MyD88, TIRAP, and TRIF was observed in the high DF group compared to the low DF group, except TRIF‐related adapter molecule. Moreover, the expression of IL‐6 and IL‐8 in the high DF group was significantly higher than low DF group, although there was no significant difference in IFN‐β and TNFα expression between the groups.

Discussion and conclusion

Damage‐associated molecular patterns from DNA damage activate TLR signaling pathway in human fallopian tubes and result in the upregulation of inflammatory cytokines and chemokines. This situation may provide pathologic environment for capacitation, fertilization, embryo development, and implantation in female reproductive tract and can be one of the mechanisms of infertility in men with high DF.
Prevalence of structural birth defects in IVF‐ICSI pregnancies resulting from autologous and donor oocytes in Indian sub‐continent: Results from 2444 births
Authors: Banker Manish , Arora Parul , Banker Jwal , Benani Hetal , Shah Sandeep , Lalitkumar Parmeswaran Grace Luther
Published: January 2019

Introduction

This study was conducted to evaluate and compare the incidence of birth defects in In‐Vitro Fertilization‐Intra Cytoplasmic Sperm Injection (IVF‐ICSI) pregnancies with autologous and donor oocytes. As a secondary outcome, the prevalence of birth defects in IVF‐ICSI pregnancies was compared with those from spontaneous conceptions in India.

Material and methods

This retrospective study included 2444 births resulting from IVF‐ICSI cycles from autologous (n = 1743) and donor oocytes (n = 701) during a 3‐year period in an Indian infertility center. Birth defects, if any, were noted antenatally and followed till the neonatal period, in case of live birth.

Results

The overall prevalence of birth defects in IVF‐ICSI pregnancies in this study was 29/2444 (118.6/10 000 births) and the most common congenital anomaly was cardiac malformation (32.7/10 000 births) followed by genitourinary (28.6/10 000 births). The risks of birth defects resulting from autologous and donor oocytes did not differ (114.7/10 000 vs 128.38/10 000; P > 0.05). However, pregnancies resulting from autologous oocytes had a higher trend of gastrointestinal birth defects (20.5/10 000 births vs 0), though not statistically significant. The risk of cardiovascular birth defects resulting from IVF‐ICSI pregnancies was much higher compared with the natural conceptions in India (32.7/10 000 vs 12.7/10 000 births; P = 0.03), whereas the risk of central nervous system malformations was much lower (8.1/10 000 vs 60.18/10 000 births; P = 0.005).

Conclusions

Overall, there was no significant difference in birth defects resulting from IVF‐ICSI with autologous or donor oocytes. The births resulting from IVF‐ICSI pregnancies did not tend to have a higher rate of birth defects a compared with natural conceptions. The differences in the prevalence of certain birth defects (cardiovascular or central nervous system) reported in IVF‐ICSI pregnancies may be due to improved surveillance modalities and early detection in pregnancies following IVF‐ICSI. A study with larger number of sample size will give us better understanding of the prevalence of reported incidence in this study.
Long‐term safety and tolerability of oral tofacitinib in patients with Crohn’s disease: results from a phase 2, open‐label, 48‐week extension study
Authors: Panés Julián , D’Haens Geert R. , Higgins Peter D. R. , Mele Linda , Moscariello Michele , Chan Gary , Wang Wenjin , Niezychowski Wojciech , Su Chinyu , Maller Eric
Published: January 2019

Background

Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease.

Aims

This 48‐week open‐label extension study primarily investigated long‐term safety of tofacitinib 5 and 10 mg b.d. and secondarily investigated efficacy as maintenance therapy in patients with Crohn's disease.

Methods

Patients who had completed the phase 2b maintenance study, or withdrawn due to treatment failure, were enrolled. Patients in remission (Crohn's disease activity index <150) at baseline received tofacitinib 5 mg b.d.; all others received 10 mg b.d. A single dose adjustment was allowed after 8 weeks’ fixed, open‐label treatment.

Results

Sixty‐two patients received tofacitinib 5 mg b.d.; 88 received 10 mg b.d. Both groups had similar rates of adverse events and serious infections. Crohn's disease worsening was the most frequent adverse event for tofacitinib 5 (33.9%) and 10 mg b.d. (19.3%). Patients not in remission at baseline, receiving 10 mg b.d., had higher rates of serious adverse events (19.3%) and discontinuation attributed to insufficient clinical response (30.7%) vs 5 mg b.d. (8.1% and 9.7%, respectively). At week 48, of patients with baseline remission receiving 5 mg b.d., 87.9% maintained remission and 75.0% sustained remission as observed (46.8% and 38.7%, respectively, by non‐responder imputation). Study design prevented between‐dose efficacy comparisons.

Conclusions

No new safety signals emerged. Although both doses showed generally similar safety outcomes for overall adverse events, serious adverse events were more frequent for tofacitinib 10 than 5 mg b.d. Discontinuation due to insufficient clinical response was lower among patients in remission at baseline. ClinicalTrials.gov: NCT01470599.
Letter: different risks of venous thromboembolism in subsets of patients with inflammatory bowel diseases – authors' reply
Authors: Chu Thomas P. C. , Grainge Matthew J. , Card Timothy R.
Published: January 2019

Linked Content

This article is linked to Chu et al and Ding et al papers. To view these articles, visit https://doi.org/10.1111/apt.15010 and https://doi.org/10.1111/apt.15083.
Disability in inflammatory bowel disease patients is associated with race, ethnicity and socio‐economic factors
Authors: Agrawal Manasi , Cohen‐Mekelburg Shirley , Kayal Maia , Axelrad Jordan , Galati Jonathan , Tricomi Brad , Kamal Kanika , Faye Adam S. , Abrudescu Paul , Scherl Ellen , Lawlor Garrett , Sultan Keith , Lukin Dana , Colombel Jean‐Frederic , Ungaro Ryan C.
Published: January 2019

Background

Race, ethnicity and socio‐economic status impact clinical outcomes in inflammatory bowel disease (IBD) patients. However, their impact on disability has not been studied.

Aim

To determine the association between race, ethnicity and socio‐economic factors with disability in IBD, using the validated IBD disability index (IBD‐DI).

Methods

Ambulatory IBD patients were enrolled at five academic centres participating in the New York Crohn's and Colitis Organization. We assessed the IBD‐DI, and collected clinical and socio‐economic data. Factors associated with moderate‐to‐severe disability (IBD‐DI score > 35) on univariable analysis were tested in multivariable models with adjusted odds ratios (aOR) and 95% confidence intervals (CI) reported.

Results

In this study, 323 patients (57.3% CD, 51.4% female) were enrolled; 17.7% were Hispanic, 17% were non‐Hispanic black, 56.0% were non‐Hispanic Caucasian and 9.3% belonged to non‐Hispanic non‐black minority races. However, 39.0% of patients were publicly insured and 38.4% of patients had low annual household income (<$50 000). 100 (31.0%) patients reported moderate‐to‐severe disability. On multivariable analysis, Hispanic ethnicity (aOR 2.7, 95% CI 1.3‐5.6), non‐Hispanic non‐black minority race (aOR 3.5, 95% CI 1.3‐8.9), public payer (aOR 2.1, 95% CI 1.1‐4.0) and low annual household income (aOR 3.0, 95% CI 1.7‐5.4) were associated with moderate‐to‐severe disability controlling for disease characteristics.

Conclusions

IBD patients who are minorities, have public insurance, or low household income, are 2‐3 times more likely to report moderate‐to‐severe disability independent of disease characteristics in the United States. Future studies are needed to study their complex relationship and to mitigate disability.
Impact of hepatitis B core‐related antigen on the incidence of hepatocellular carcinoma in patients treated with nucleos(t)ide analogues
Authors: Hosaka Tetsuya , Suzuki Fumitaka , Kobayashi Masahiro , Fujiyama Shunichirou , Kawamura Yusuke , Sezaki Hitomi , Akuta Norio , Suzuki Yoshiyuki , Saitoh Satoshi , Arase Yasuji , Ikeda Kenji , Kobayashi Mariko , Kumada Hiromitsu
Published: January 2019

Background

Chronic hepatitis B virus (HBV) infection is an aetiologic factor for hepatocellular carcinoma (HCC). Baseline HBV DNA is a known independent predictor of HCC, and the serum hepatitis B core‐related antigen (HBcrAg) level corresponds to intrahepatic covalently closed circular DNA.

Aim

To investigate whether the baseline and on‐treatment serum HBcrAg levels can predict HCC incidence in patients with chronic hepatitis B following nucleos(t)ide analogue (NA) therapy.

Methods

This retrospective cohort study included 1268 patients treated with NAs for >1 year. In all patients, serum HBcrAg and hepatitis B surface antigen levels were measured at baseline and 1 year.

Results

During a median follow‐up of 8.9 years, 113 patients (8.9%) developed HCC (10.3/1000 person‐years). These patients were stratified by baseline hepatitis B e‐antigen (HBeAg) status into HBeAg+ and HBeAg‐ cohorts. High on‐treatment HBcrAg levels at 1 year were found to associate significantly with HCC (HBeAg+ cohort: P = 0.017; HBeAg‐ cohort: P = 4.30 × 10−5; cut‐off values: 4.9 log U/mL and 4.4 log U/mL, respectively). In a multivariate Cox regression analysis, patients with persistently high on‐treatment HBcrAg levels had a higher risk of HCC than those with low HBcrAg levels (HBeAg+: hazard ratio [HR], 6.15, 95% confidence interval [CI]: 1.89‐20.0, P = 0.003; HBeAg‐ cohort: HR, 2.54, 95% CI: 1.40‐4.60; P = 0.002). A sub‐analysis of patients without alcoholism yielded similar findings.

Conclusions

Patients with persistently high on‐treatment HBcrAg levels were more likely to develop HCC despite sustained viral suppression via long‐term NA treatment.
Vedolizumab exposure levels and clinical outcomes in ulcerative colitis: determining the potential for dose optimisation
Authors: Osterman Mark T. , Rosario Maria , Lasch Karen , Barocas Morris , Wilbur Jayson D. , Dirks Nathanael L. , Gastonguay Marc R.
Published: January 2019

Background

Prospectively designed studies assessing the exposure‐response profile of vedolizumab are lacking. Observational exposure‐response data for vedolizumab are limited and have not been adjusted for potential confounding factors, particularly those that may affect vedolizumab clearance.

Aims

To (a) investigate the vedolizumab exposure‐response relationship after adjusting for potential confounding variables; (b) propose potential target serum vedolizumab concentrations for future study; (c) ascertain whether early vedolizumab serum concentrations were associated with short‐ and long‐term clinical outcomes in adults with ulcerative colitis in GEMINI 1.

Methods

Propensity‐score‐based case‐matching analysis was performed using data from GEMINI 1 and an earlier large population pharmacokinetic study, with vedolizumab clearance or concentration as predictors of clinical remission and response, adjusted for age, weight, anti‐tumour necrosis factor alpha therapy history, serum albumin and faecal calprotectin concentrations. Potential vedolizumab concentration targets at weeks 6, 14 and steady state were proposed. Association between early vedolizumab concentrations at weeks 2, 4 and 6 and clinical remission at weeks 14 and 52 was evaluated.

Results

Among 693 patients with pharmacokinetic data at week 6, potential target vedolizumab concentrations at weeks 6, 14 and steady state were 37.1, 18.4 and 12.7 µg/mL respectively. Week 6 was identified as the earliest time at which vedolizumab concentrations were consistently associated with clinical remission at weeks 14 and 52.

Conclusions

In this comprehensively adjusted analysis, vedolizumab concentrations at week 6 were associated with short‐ and long‐term remission. Potential induction and maintenance target concentrations were proposed for further study.
Video‐assisted esophagectomy using a port‐free organ retractor for the prevention of laryngeal nerve paralysis
Authors: Sato Shinsuke , Nagai Erina , Taki Yusuke , Watanabe Masaya , Takagi Masakazu
Published: January 2019

Introduction

Recurrent laryngeal nerve (RLN) paralysis is a major complication of esophageal cancer surgery. The free jaw clip (FJ clip) was developed as an organ‐retracting device, and it can also reduce the number of ports required during surgery. Here, we describe a new technique for lymphadenectomy along the left RLN using the FJ clip.

Materials and Surgical Technique

After the middle and lower mediastinal lymph nodes were dissected, the upper esophagus and other tissues, including the lymph nodes and left RLN, were retracted by cutting the tracheal arteries between the esophagus and trachea and then pulling the upper esophagus to the dorsal side with the FJ clip. The esophagus was transected at the upper mediastinum, and the proximal esophagus was drawn by the FJ clip. This technique helped provide a good field of view during lymphadenectomy along the left RLN. The data of nine consecutive patients who underwent video‐assisted esophagectomy in the left lateral decubitus position by the same surgeon were reviewed. Postoperative left RLN paralysis occurred in only one patient in whom the RLN could not be preserved.

Discussion

Given the excellent short‐term outcomes with respect to left RLN paralysis, lymphadenectomy along the left RLN using the FJ clip was safe and feasible.
Vegetation changes over the past two decades in a West African savanna ecosystem
Authors: Leßmeister Anna , Bernhardt‐Römermann Markus , Schumann Katharina , Thiombiano Adjima , Wittig Rüdiger , Hahn Karen
Published: January 2019

Questions

West African savanna ecosystems are affected by increasing land use intensity (e.g., agriculture and livestock herds) due to a growing human population. To understand the impact of land use intensification on savanna vegetation, we aim to answer the following questions: How do savanna species composition, diversity and structure change with increasing land use pressure? Are the impacts of land use change different in the woody and the herbaceous layers? Do the effects of land use change differ between vegetation types?

Location

Southeastern Burkina Faso, West Africa.

Methods

Vegetation plots from the early 1990s representing vegetation types occurring in fallows of different age and in uncultivated pasturing zones were resurveyed. We distinguished between woody (tree and shrub layer) and herbaceous vegetation types. Species composition changes were analyzed using ordination techniques (detrended correspondence analysis, DCA) and indicator species analysis (IndVal). Species turnover and plant diversity as represented by species richness and evenness were compared between the baseline survey and the resurvey.

Results

In most woody vegetation types, we found no change in species composition and richness over the past two decades. However, some highly valued woody species decreased in abundance. In contrast, in most herbaceous vegetation types, species composition changed considerably and species richness increased. The proportion of wide‐ranging, ruderal herbaceous species increased, indicating a homogenization of herbaceous vegetation types, while preferred fodder herbaceous species decreased. We assume that the increased grazing intensity over the past two decades is the driver of these changes in the herbaceous layer.

Conclusions

Our results show different reactions of vegetation types and layers to land use intensification and reinforce the need for studies on the basis of vegetation type that incorporate both the herbaceous and the woody layers.
Has the frequency of invasive higher plants stabilized? Results from a long‐term monitoring program of Danish habitats
Authors: Damgaard Christian , Nygaard Bettina , Ejrnæs Rasmus , Bruus Marianne , Strandberg Beate , Strandberg Morten , Timmermann Allan , Ehlers Bodil K
Published: January 2019

Questions

The change in the frequencies of invasive higher plant species in different habitat types was investigated using Danish monitoring data from 2004 to 2014.

Location

Denmark.

Methods

The occurrence data were collected in circles with a radius of 5 m at a number of plots within 923 sites. The sampling intensity was irregular with sampling intervals ranging from one to three years. The hierarchical occurrence data were fitted in a hierarchical model, where the site‐specific occurrence probabilities were modelled by latent variables.

Results

The overall frequency of invasive higher plant species increased significantly in this 11‐year period in two of the seventeen habitat types, i.e. on coastal dunes and on dry heathland. The frequency of the dominating invasive species, Rosa rugosa, Pinus contorta, and Prunus serotina, was observed to increase significantly in three, two, and one out of the seventeen habitat types, respectively, whereas the frequency of Pinus mugo was found to decrease significantly in one habitat type.

Conclusions

The frequency of invasive higher plant species has not stabilized and is still increasing in some or several Danish habitat types. Furthermore, trend analyses of a selected subset of invasive plant species may serve as an important early warning signal that may be used in the management of ecosystems.
Vegetation connectivity increases ant activity and potential for ant‐provided biocontrol services in a tropical agroforest
Authors: Jimenez‐Soto Estelí , Morris Jonathan R. , Letourneau Deborah K. , Philpott Stacy M.
Published: January 2019

In natural and managed systems, connections between trees are important structural resources for arboreal ant communities with ecosystem‐level effects. However, ongoing agricultural intensification in agroforestry systems, which reduces shade trees and connectivity between trees and crop plants, may hinder ant recruitment rates to resources and pest control services provided by ants. We examined whether increasing connectivity between coffee plants and shade trees in coffee plantations increases ant activity and enhances biological control of the coffee berry borer, the most devastating insect pest of coffee. Further, we examined whether artificial connections buffer against the loss of vegetation connectivity in coffee plants located at larger distances from the nesting tree. We used string to connect Inga micheliana shade trees containing Azteca sericeasur ant nests to coffee plants to compare ant activity before and after placement of the strings, and measured borer removal by ants on coffee plants with and without strings. Ant activity significantly increased after the addition of strings on connected plants, but not on control plants. Borer removal by ants was also three times higher on connected plants after string placement. Greater distance from the nesting tree negatively influenced ant activity on control coffee plants, but not on connected plants, suggesting that connections between coffee plants and nest trees could potentially compensate for the negative effects that larger distances pose on ant activity. Our study shows that favoring connectivity at the local scale, by artificially adding connections, promotes ant activity and may increase pest removal in agroecosystems.

Abstract in Spanish is available with online material.
Plasmodium falciparum: Multidrug resistance
Authors: Rout Subhashree , Mahapatra Rajani Kanta
Published: January 2019

Malaria is the most lethal and debilitating disease caused by the protozoan parasite Plasmodium worldwide. The most severe forms of disease and the incidence rates of mortality are associated with P. falciparum infections. With the identification of disease source and symptoms, many chemical entities were developed naturally and synthetically for administration as a potential antimalarial drug. The major classes of approved antimalarial drugs that are governed as first‐line treatment in tropical and subtropical areas include quinolines, naphthoquinones, antifolates, 8‐aminoquinolines, and endoperoxides. However, the efficacy of antimalarial drugs has decreased due to ongoing multidrug resistance problem to current drugs. With increasing resistance to the current antimalarial artemisinin and its combination therapies, malaria prophylaxis has declined gradually. New‐generation antimalarial and novel drug target are required to check the incidence of malaria resistance. This review summarizes the emergence of multidrug resistance to known antimalarial and the development of new antimalarial to resolve drug resistance condition. Few essential proteins are also discussed that can be considered as novel drug target against malaria in future.
Acceptability and understanding of the Ages & Stages Questionnaires®, Third Edition, as part of the Healthy Child Programme 2‐year health and development review in England: Parent and professional perspectives
Authors: Kendall Sally , Nash Avril , Braun Andreas , Bastug Gonca , Rougeaux Emeline , Bedford Helen
Published: January 2019

Background

The Healthy Child Programme is the universal public health system in England to assess and monitor child health from 0 to 19. Following a review of measures for closer monitoring at age 2 years, the Department of Health for England implemented the Ages & Stages Questionnaires®, Third Edition (ASQ‐3™; Hereon, ASQ‐3).

Aim

The aim of this study was to evaluate the acceptability and understanding of the ASQ‐3 in England by health professionals and parents.

Method

A mixed‐methods approach was used. This paper reports on the qualitative data drawn from interviews with 40 parents and 12 focus groups with 85 health professionals. The data were analysed using applied thematic analysis.

Findings

Overall, parents and health professionals found the ASQ‐3 acceptable and understandable and could use it as a measure at age 2 years. The ability to work in partnership was valued.

Some limitations included potential to cause anxiety, concerns around the safety of some of the items, and use of Americanized language. Health professional's training in the use the ASQ‐3 was inconsistent.

Conclusion

The ASQ‐3 is an acceptable and understandable measure to use as part of the 2‐year assessment with some adaptations to the English context and some standardized training for health professionals.
A single administration of human adipose tissue-derived mesenchymal stromal cells (MSC) induces durable and sustained long-term regulation of inflammatory response in experimental colitis
Authors: Alves V B Freitas , de Sousa B Coutinho , Fonseca M Thaís Costa , Ogata H , Caliári-Oliveira C , Yaochite J Navarro Ueda , Rodrigues Júnior V , Chica J E Lazo , da Silva J Santana , Malmegrim K C Ribeiro , Pernomian L , Cardoso C Ribeiro
Published: January 2019

Current therapies for inflammatory bowel diseases (IBD) are aimed at controlling the exacerbated response in the gut, but no treatment is fully effective for many refractory patients. Mesenchymal stromal cells (MSC) are multi-potent cells with regulatory immunosuppressive activity that may control inflammatory diseases. In this study, we investigated the short- and especially the long-term protective effects of MSC on experimental colitis. We show that MSC elicited protection to acute intestinal inflammation with gain of weight, improvement in the clinical disease score and expressive reduction in the mortality rate of treated mice. MSC changed the population of neutrophils, eosinophils and augmented the frequency of CD4 T lymphocytes in the gut-draining lymph nodes, together with reduced accumulation of these cells in the colon intraepithelial compartment. Interestingly, there were increased levels of programmed death 1 (PD-1) and glucocorticoid-induced tumour necrosis factor receptor family-related receptor (GITR) in the spleen regulatory T cells of mice that received MSC treatment, which also presented a reversal in the pattern of immune response in the gut, with diminished inflammatory, T helper type 1 (Th1) and Th17 profile, in contrast to augmented Th2 responses. Most strikingly, this balanced response elicited by a single administration of MSC during the acute colitis persisted long-term, with restored goblet cells, eosinophils and maintenance of elevated gut interleukin (IL)-4, besides increased CD4+CD25+PD-1+ cells in the spleen and reduced Th17 response in mesenteric lymph nodes (MLN) of treated mice on day 60. Taken together, our findings provided a significant contribution to translational immunology by pointing human adipose tissue-derived MSC as a novel therapeutic approach with long-term beneficial regulatory effects in experimental colitis.
Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as haematological indices of inflammatory response in ceramic workers’ silicosis
Authors: Karataş Mevlüt , Gündüzöz Meşide , Öziş Türkan Nadir , Özakıncı Osman Gökhan , Ergün Dilek
Published: January 2019

Introduction

Occupational exposure to crystalline silica over time may result in silicosis: a fatal, irreversible occupational disease leading to lung function impairment. A complex inflammatory process, excessive accumulation of mesenchymal cells and collagen production are the primary mechanisms underlying silicosis. Neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) have emerged as representative indices of systemic inflammation.

Objectives

The purpose of the present study was to investigate the relationship between NLR, PLR and silicosis.

Methods

We retrospectively analysed the demographic and laboratory data of ceramic workers who were referred to our Hospital between 2010 and 2018. Five hundred and seventy‐three patients with silicosis and 222 ceramic workers without silicosis (controls) were included in the study.

Results

The radiographic ILO classification of silicosis patients was as follows: category 1 (71.5%), category 2 (19.2%), category 3 (7.5%). NLR and PLR in categories 2 and 3 were significantly higher when compared with the control group (P < .005). FEV1, FEV1%, FVC, FVC % and PEF were significantly lower in all silicosis patients and also in patients with subcategories (all P < .005). NLR showed a poor positive correlation with CRP (r = 0.095, P < .05) and ESR (r = 0.207, P = .000) while PLR only with ESR (r = 0.317, P = .000) in patients with silicosis. NLR and PLR showed negative correlations with FEV1, FVC and PEF (all P < .005).

Conclusion

We conclude that NLR and PLR have significant but poor correlations with pulmonary functions and severity of silicosis, especially in late radiographic profusion categories.
Solitary and multiple epidermolytic acanthoma: A demographic and clinical study of 131 cases
Authors: Roy Simon F. , Ghazawi Feras M. , Choate Keith A. , McNiff Jennifer M.
Published: January 2019

BACKGROUND

Epidermolytic acanthoma (EA) is a rare, benign acquired cutaneous keratosis displaying epidermolytic hyperkeratosis in more than 50% of its surface. Because of the sparsity of comprehensive studies, little is known on the patient demographics and clinical characteristics of this uncommon entity. We wish to comprehensively characterize the clinical and demographic features of EA and to differentiate it from its mimickers.

METHODS

We carried out a retrospective review of 131 cases of EA, recorded clinical and histopathologic features and performed linear regression of yearly incidence rates to assess for possible under‐reporting of this entity.

RESULTS

EA affected both genders equally. We found 9.08 cases per 100 000 biopsy specimens per year and linear regression analysis showed significantly decreasing incidence rates. Analysis of the anatomical site distribution of EA lesions showed a more frequent genital location in men (39.1% of cases in men, as compared to 11.3% for women). Contrary to previous studies, lesions were most frequently single (91.7%) and the mean age of presentation was 57.8 years.

CONCLUSION

The presented largest case series to‐date indicates that EA is probably an underdiagnosed entity and establishes the demographic and clinical features of EA.
New application of dual knife: Easier removal of a giant gastric bezoar
Authors: Tao Zhang , Yu Yiwen , Zhou Xiaoqing
Published: January 2019

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The future of disasters studies: new disasters and the case of the Horn of Africa
Authors: Kuol Luka
Published: January 2019

Past disasters have been well studied, but the challenge of using the findings to improve the management of future events remains a daunting task. This paper argues that there are new and complex disasters of which the state itself has become the main source, as reflected in the Horn of Africa. This region is characterised by increasing vulnerability owing to the alarming decline of democracy and the rise of authoritarianism. These new disasters are less researched because of the hazard of conducting fieldwork in such environments. However, there is mounting evidence to highlight the possibility of performing research in these settings, but not by employing traditional methods; rather, these tools may need to be customised for use. One key policy implication here is that donors may need to invest more money in analysing these new disasters and they may need to consider building and strengthening genuine partnerships between Northern and Southern research institutions
The best care for children with facioscapulohumeral dystrophy
Authors: Bernardino Gomes Tiago
Published: January 2019

This commentary is on the original article by Steel et al. on pages 964–971 of this issue.
Fifty years’ follow‐up of childhood epilepsy: Medical outcome, morbidity, and medication
Authors: Brorson Lars‐Olov , Eriksson Mats , Blomberg Karin , Stenninger Erik
Published: January 2019

Objective

To describe the long‐term prognosis of childhood epilepsy, with special emphasis on seizure remission, relapse, medication, associated neurologic impairment, mortality rate, and cause of death.

Methods

A prospective longitudinal study on a population‐based total cohort of 195 children with epileptic seizures in 1962‐1964. Data were collected from medical records and a questionnaire.

Results

Follow‐up data from 94% of the initial cohort showed the best long‐term prognosis for seizure freedom for children with no intellectual or neurologic impairment. These children had later seizure onset, shorter total duration of epilepsy, and were more often medication free. Only a few of them had isolated relapses. Generalized, rather than focal, epilepsy was associated with fewer relapses and less ongoing medication. The “true incidence” group, with onsets during the inclusion period of 1962‐1964, had the best long‐term prognosis for seizure freedom, with 90% seizure‐free after 50 years. Although only 10% of this group had ongoing seizures at follow‐up, 22% still used anticonvulsive medication, often with old drugs, that is, phenobarbital or phenytoin, as one of the anticonvulsive drugs. The standardized mortality ratio (SMR) was 2.61 for the whole group, with no difference between those with or without other neurodeficits. Those who died young either had neurologic impairment or died from epilepsy‐related conditions; later deaths often followed non–epilepsy‐related conditions. No one in the incidence group died of SUDEP (sudden unexpected death in epilepsy).

Significance

This 50‐year, long‐term follow‐up of a cohort of persons with childhood epilepsy in general demonstrates a better outcome for seizure freedom compared to our follow‐up after 12 years and to previous reports. We also report a low incidence of seizure relapses. Remission of seizures does not automatically lead to termination of medication. The mortality rate associated with SUDEP was lower than previously reported.
Drug repurposing for Dravet syndrome in scn1Lab−/− mutant zebrafish
Authors: Sourbron Jo , Partoens Michèle , Scheldeman Chloë , Zhang Yifan , Lagae Lieven , de Witte Peter
Published: January 2019

Dravet syndrome (DS) is a severe genetic epileptic encephalopathy with onset during the first year of life. Zebrafish models recapitulating human diseases are often used as drug discovery platforms, but also for drug repurposing testing. It was recently shown that pharmacological modulation of three serotonergic (5‐HT) receptors (5‐HT1D, 5‐HT2C, 5‐HT2A) exerts antiseizure effects in a zebrafish scn1Lab−/− mutant model of DS. Using the zebrafish DS model, our aim was to examine the possibility of repurposing efavirenz (EFA), lisuride (LIS), and rizatriptan (RIZA), marketed medicines with a 5‐HT on‐ or off‐target profile, as antiepileptic drugs for DS. To examine whether these compounds have a broader antiseizure profile, they were tested in pentylenetetrazol and ethyl ketopentenoate (EKP) zebrafish models. Pharmacological effects were assessed by locomotor behavior, local field potential brain recordings, and bioluminescence. EFA was active in all models, whereas LIS was selectively active in the zebrafish DS model. Mainly, a poor response was observed to RIZA. Taken together, our preclinical results show that LIS could be a potential candidate for DS treatment. EFA was also active in the EKP model, characterized by a high level of treatment resistance, and hence these data are potentially important for future treatment of drug‐resistant epilepsy.
MiR‐744‐3p regulates keratinocyte proliferation and differentiation via targeting KLLN in psoriasis
Authors: Wang Changyuan , Zong Jinbao , Li Yongxi , Wang Xiaoyan , Du Weihua , Li Linfeng
Published: January 2019

Psoriasis is a chronic inflammatory disease, and microRNAs have been reported to regulate the pathogenesis of psoriasis. Up‐regulated miR‐744‐3p level was identified to associate with psoriasis while the precise functions of miR‐744‐3p in psoriasis were not well‐elucidated. We first confirmed the up‐regulation of miR‐744‐3p in psoriasis by measuring its expression level in psoriatic samples. We explored the roles of miR‐744‐3p on keratinocytes proliferation and differentiation. We searched the targets of miR‐744‐3p and evaluated the roles of one target, KLLN on keratinocytes proliferation and differentiation. We confirmed the up‐regulation of miR‐744‐3p in psoriatic samples. MiR‐744‐3p promoted keratinocytes proliferation while inhibited differentiation. MiR‐744‐3p targeted KLLN and overexpression of miR‐744‐3p resulted in decreased expression of KLLN. Overexpression of KLLN prevented the effects of miR‐744‐3p on keratinocytes proliferation and differentiation. MiR‐744‐3p regulated the proliferation and differentiation of keratinocytes through targeting KLLN in psoriasis.