bluuebunny/crossref_metadata_2025 huggingface dataset:
Co‐existence of Marfan syndrome and systemic sclerosis: A case report and a hypothesis suggesting a common link
Authors: Yap Wee Fang , Chong Hwee Cheng
Published: September 2020

FBN1 gene encodes for the connective tissue protein fibrillin‐1 which can also regulate the profibrotic cytokine transforming growth factor (TGF)‐ß1. Mutations in the FBN1 gene cause Marfan syndrome (MFS), a genetic condition with defective connective tissues. FBN1 haplotypes and single nucleotide polymorphisms have also been reported to be associated with systemic sclerosis (SSc), a connective tissue disease characterized by fibrosis of multiple organs. Furthermore, the duplication of the Fbn1 gene causes a SSc‐like disease in the TsK1 mouse model. To the best of our knowledge, there are no reports of MFS and SSc co‐existing in a patient. Here, we describe a 46‐year‐old woman who presented with cardiac failure. She had a family history of MFS. Physical examination revealed marfanoid habitus and scleroderma features. Echocardiography demonstrated dilated cardiomyopathy with aortic root dilatation, aortic regurgitation and mitral regurgitation. Cardiac magnetic resonance imaging was consistent with dilated cardiomyopathy, mid‐wall fibrosis at basal septal wall and dilated aortic root. Extractable nuclear antigen panel detected anti‐Scl 70. She fulfilled Ghent criteria for MFS and satisfied American College of Rheumatology/ European League Against Rheumatism classification criteria for SSc. Although we do not have the FBN1 sequence in our patient, the co‐existence of MFS and SSc in this patient raises the possibility of co‐existence of distinct mutations in the FBN1 gene that could affect TGF‐β signaling differently, resulting in divergent pathologic consequences – loss of structural integrity in MFS versus increased extracellular matrix deposition in SSc, and different clinical manifestations.
Cardiovascular morbidity and mortality in patients with spondyloarthritis: A meta‐analysis
Authors: Kim Ji Hyoun , Choi In Ah
Published: September 2020

Aim

Cardiovascular (CV) risk and mortality associated with spondyloarthritis (SpA) remain controversial. Herein, we performed a meta‐analysis of the latest large‐scale population‐based studies to demonstrate the elevated risk of CV disease and mortality in patients with SpA than in the general population.

Methods

MEDLINE and EMBASE databases were searched systematically for population‐based studies published between January 1997 and September 2019. Additional manual literature searches were also performed. All searches and data collection were performed independently by 2 reviewers. We calculated the risks of myocardial infarction (MI), stroke, and all‐cause mortality in a meta‐analysis and determined the risk ratios (RR) using the Mantel–Haenszel method.

Results

Among the 641 identified articles, 16 articles involving 18 cases met the inclusion criteria for our meta‐analysis; these included 12 cases of ankylosing spondylitis, five cases of psoriatic arthritis, and 1 case of undifferentiated SpA. Our meta‐analysis revealed a significantly high risk of MI (RR: 1.52; 95% CI: 1.29‐1.80) and stroke (RR: 1.21; 95% CI: 1.0‐1.47) in patients with SpA than in the general population. However, this increased risk was not significant in terms of all‐cause mortality (RR: 1.23; 95% CI: 0.96‐1.57).

Conclusions

Our meta‐analysis demonstrated that patients with SpA have a significantly increased risks of MI and stroke, but without a significant increase in the all‐cause mortality, than that in the general population. The higher risk of CV in patients with SpA than that in the general population indicates the need for strict risk factor correction and disease management.
Growth of Stenotrophomonas maltophilia and expression of Sme efflux pumps encoding genes in the presence of supernatants from amoebal and bacterial co‐cultures: towards the role of amoebal secondary metabolites
Authors: Denet Elodie , Triadou Sylvain , Michalet Serge , Nazaret Sylvie , Favre‐Bonté Sabine
Published: September 2020

Resistance‐Nodulation‐Division (RND) efflux pumps are relevant determinants of Stenotrophomonas maltophilia multidrug resistance as they can extrude a broad range of antibiotics and compounds involved in virulence and physiological functions. S. maltophilia, an environmental bacterium, was shown to be associated with amoebae and able to multiply inside them. To explore whether S. maltophilia RND efflux pumps play a role when interacting with amoebae, we evaluated the effect of amoebal culture and co‐culture supernatants on the growth of S. maltophilia and the expression of sme efflux pump genes. Acanthamoeba castellanii and Willaertia magna were used as amoebal models and strain S. maltophilia BurE1 as bacterial one. Our data showed that both bacterial growth and sme gene expression were not modified by amoebal culture supernatants. On the contrary, co‐culture supernatants negatively impacted the growth of BurE1 and induced the expression of three out of eight efflux pump genes, i.e. smeE, smeN and smeZ. Finally, we evidenced the production of A. castellanii secondary metabolites, putatively belonging to the diterpene family, in the amoebal supernatant and in the co‐culture supernatant of A. castellanii and BurE1. Whether these compounds act directly as substrates of the efflux pumps and/or inducers of the sme genes need further investigations.
AIDE: Accelerating image‐based ecological surveys with interactive machine learning
Authors: Kellenberger Benjamin , Tuia Devis , Morris Dan
Published: September 2020

Ecological surveys increasingly rely on large‐scale image datasets, typically terabytes of imagery for a single survey. The ability to collect this volume of data allows surveys of unprecedented scale, at the cost of expansive volumes of photo‐interpretation labour.

We present Annotation Interface for Data‐driven Ecology (AIDE), an open‐source web framework designed to alleviate the task of image annotation for ecological surveys. AIDE employs an easy‐to‐use and customisable labelling interface that supports multiple users, database storage and scalability to the cloud and/or multiple machines.

Moreover, AIDE closely integrates users and machine learning models into a feedback loop, where user‐provided annotations are employed to re‐train the model, and the latter is applied over unlabelled images to e.g. identify wildlife. These predictions are then presented to the users in optimised order, according to a customisable active learning criterion. AIDE has a number of deep learning models built‐in, but also accepts custom model implementations.

Annotation Interface for Data‐driven Ecology has the potential to greatly accelerate annotation tasks for a wide range of researches employing image data. AIDE is open‐source and can be downloaded for free at https://github.com/microsoft/aerial_wildlife_detection.
Carfentanil and the rise and fall of overdose deaths in the United States
Authors: Jalal Hawre , Burke Donald S.
Published: September 2020

Background and Aims

It is widely believed that the 2018 decline in overdose deaths in the United States was attributable to a range of public health interventions, however, this decline also coincided with the regulation and decline in use of potent fentanyl analogs, especially carfentanil. The aim of this study was to investigate the association between overdose deaths and carfentanil availability in the United States.

Design

Secondary analysis of drug overdose deaths from the Center for Disease Control and Prevention (CDC) and carfentanil exhibit data from drug seizures submitted to drug crime labs and published by the Drug Enforcement Administration (DEA). Trends in overdose deaths were compared in states with high carfentanil exhibits with states with low or no carfentanil exhibits.

Setting

United States.

Participants

A total of 1 035 923 drug overdose death records in the United States from 1979 through 2019 were studied.

Measurements

The outcomes studied were number of overdose deaths and mortality rates by state.

Findings

Drug overdose deaths have been closely tracked along an exponential curve. The years 2016 and 2017 witnessed a hyper‐exponential surge with increases in overdose deaths of 11 228 (+21.4%) and 6605 (+10.4%), respectively. Subsequently in 2018, drug overdose deaths declined by −2870 (−4.1%). This rise and then fall coincided with a surge and then decline in carfentanil drug seizure exhibits during these same years: 0 (2015), 1292 (2016), 5857 (2017) and 804 (2018). The majority of carfentanil exhibits were localized to a few states. The 2018 decline in overdose deaths in the top five states with the greatest spike in carfentanil exhibits in 2017 (Ohio, Florida, Pennsylvania, Kentucky and Michigan) was 2848, which accounted for nearly all of the total US decline.

Conclusions

The 2016–2017 acceleration and then 2018 decline in drug overdose deaths in the United States was associated with the sudden rise and then fall of carfentanil availability. Given the regional variation, carfentanil's decreased availability may have contributed to the reduction in overdose deaths in 2018.
The incidence and patterns of gastric cancers in Sri Lanka from 2001 to 2012: Analysis of National Cancer Registry Data
Authors: Jayarajah Umesh , Fernando Ashan , Samarasekera Dharmabandhu N. , Seneviratne Sanjeewa
Published: September 2020

Objectives

Varying patterns in incidence of gastric cancer (GC) have been reported globally. We aimed to examine the trends of GC incidence in Sri Lanka.

Methods

All newly diagnosed patients with GC in Sri Lanka during 2001‐2012 included in the National Cancer Registry were analyzed. Joinpoint regression analysis was used to determine the trends in incidence by age and gender. The minimum number of joinpoints were added to the model and statistical significance was checked using the Monte‐Carlo permutation method.

Results

Overall, 3353 (male : female = 2.7:1, mean age: 59.5 years) GCs were included in the analysis. Histology findings were available in 2835 patients. Of those, 14.3% (n = 404) were classified as nonspecified neoplasm/carcinoma. Of the remaining 2431 patients, majority (84.1%, n = 2044) were adenocarcinoma/its variants and 9.4% (n = 228) were squamous cell carcinoma. The WHO age‐standardized incidence of GC was found to have significantly increased from 1.06 in 2001 (95% CI = 0.9‐1.21) to 2.41/100 000 population in 2012 (95% CI = 2.2‐2.61); with an estimated annual percentage change (EAPC) of 7.7 (95% CI = 6.1‐9.4). Highest incidence of GC was seen in 65‐69 year age group (8.2/100 000). The proportional rise in incidence was higher for females (from 0.5 to 1.36, EAPC: 9.0 [95% CI = 6.4‐11.8], P < .05 for trend) compared with males (from 1.71 to 3.66, EAPC: 7.5 [95% CI = 5.5‐9.6], P < .05 for trend).

Conclusions

A rise in the incidence of GC was noted in Sri Lanka during the period 2001‐2012, which was predominately observed in females. A combination of true increase in incidence and improved reporting may have contributed to this increase. Future studies analyzing tumor characteristics and mortality would enable better understand the burden of GC and potential underlying reasons.
Efficacy of cabazitaxel and the influence of clinical factors on the overall survival of patients with castration‐resistant prostate cancer: A local experience of a multicenter retrospective study
Authors: Takai Manabu , Kato Seiichi , Nakano Masahiro , Fujimoto Shota , Iinuma Koji , Ishida Takashi , Taniguchi Mitsuhiro , Tamaki Masayoshi , Uno Masahiro , Takahashi Yoshito , Komeda Hisao , Koie Takuya
Published: September 2020

Aim

To date, the optimal sequencing of life‐prolonging therapies for patients with metastatic castration‐resistant prostate cancer (mCRPC) remains unclear owing to a lack of prospective trials. This study aimed to evaluate the efficacy and safety of cabazitaxel (CBZ) treatment and examine the prognostic factors for oncological outcomes in patients with mCRPC who received CBZ after docetaxel (DOC).

Methods

This multi‐institutional retrospective study included 44 patients with mCRPC who received CBZ. All enrolled patients had histologically confirmed prostate cancer (PCa) with distant metastases and had received DOC before CBZ administration. The primary endpoint was the oncological outcomes, including the overall (OS) and progression‐free survival (PFS). The secondary endpoints were adverse events due to CBZ and rates of ≥30% reduction in prostate‐specific antigen (PSA) levels.

Results

The median follow‐up period was 9.2 months (range, 0.2–34 months). During this time, 34 patients (77%) died of PCa. The median OS and PFS were 12.2 (range, 0.2–34 months) and 1.4 months (range, 0.4–17 months), respectively. According to the PSA decline rate, patients who achieved a ≥30% reduction in PSA levels had significantly longer OS than those who showed a <30% reduction in PSA levels (P = 0.002). Regarding the number of cycles of CBZ, patients who received ≥4 cycles of CBZ showed significantly longer OS than those who received <4 cycles of CBZ (P < 0.001). Patients who had visceral metastasis showed significantly shorter OS than those without visceral metastasis (P = 0.012).

Conclusion

This study demonstrated that CBZ was effective and safe in Japanese local patients in a real‐world setting. Patients with mCRPC who received ≥4 cycles of CBZ showed a ≥30% reduction in the serum PSA levels, and did not have visceral metastasis might achieve longer OS.
Increased rates of cetuximab reactions in tick prevalent regions and a proposed protocol for risk mitigation
Authors: Yuile Alexander , Fanuli Claudia , van Nunen Sheryl , Diakos Connie , Clarke Stephen , Steiner Christian , MacMillan Robyn , Oatley Meredith , Pavlakis Nick
Published: September 2020

Background

Cetuximab is an anti‐epidermal growth factor receptor mouse‐human chimeric monoclonal antibody used to treat advanced colorectal cancers. Initial data suggest that severe infusion reactions occurred in 4.5%, many on first exposure. The majority of those with anaphylactic reactions possess predeveloped IgE antibodies to galactose‐alpha‐1,3‐galactose. It is thought that the vector for preexposure to alpha‐gal is antigen inoculation via tick bites. This retrospective study reviews the experience of two community cancer centers in high tick exposure areas in Sydney with cetuximab anaphylaxis and proposes a protocol to avoid this.

Method

Severe cetuximab infusion reactions occurring in the Northern Cancer Institute Frenchs Forest and St Leonards clinics, Sydney, from May 2014 to February 2019 were recorded. Area of residence was then compared to areas of known high tick prevalence.

Results

A total of 87 patients received cetuximab in this period. Six patients (6.9%) experienced at least a grade 3 reaction, three females, age range 41–72 years (median 57.5 years). All were receiving cetuximab for metastatic colorectal cancer and their anaphylaxis occurred with the first infusion in all cases.

Conclusion

These cases support the existing theory of increased rates of cetuximab anaphylaxis in areas of high tick prevalence. Given this, we recommend the following protocol for patients being considered for cetuximab therapy: known mammalian meat allergy as an absolute contraindication; all patients receiving cetuximab should have RAST (ImmunoCAP®) testing for alpha‐gal specific‐IgE‐specific antibodies before first infusion and those who test positive to be considered alternate therapy.
Cytotrophoblasts suppress macrophage‐mediated inflammation through a contact‐dependent mechanism
Authors: Eastman Alison J. , Vrana Erin N. , Grimaldo Maria T. , Jones Amanda D. , Rogers Lisa M. , Alcendor Donald J. , Aronoff David M.
Published: September 2020

Problem

Gestational membrane (GM) infection provokes inflammation and can result in preterm prelabor rupture of membranes (PPROM). The choriodecidual layer of the GM includes decidual stromal cells (DSC), cytotrophoblasts (CTB), and macrophages (Mφ). Our laboratory has previously shown that DSCs suppress Mφ TNF‐α production through secreted prostaglandin E2. We hypothesized that CTBs would also inhibit Mφ cytokine expression through secreted mediators.

Method of Study

THP.1 Mφ‐like cells with an NF‐κB reporter construct or human blood monocyte‐derived Mφ were co‐cultured with the Jeg3 CTB cell line or primary human CTBs and challenged with group B streptococcus (GBS) or Toll‐like receptor (TLR) agonists. Conditioned medium generated from CTB cultures was applied to Mφ cultures before infection or treatment. Alternatively, CTBs were co‐incubated with, but physically separated from, Mφ and GBS or TLR‐stimulated. NF‐κB was assessed via alkaline phosphatase assay, and proinflammatory mediators were assessed by qRT‐PCR and ELISA.

Results

CTBs suppressed GBS‐ or TLR‐stimulated Mφ NF‐κB activity, and TNF‐α and MMP9 production. Direct physical contact between CTBs and Mφ was required for full immunosuppression. Immunosuppression could be overcome by increasing the ratio of Mφ to CTB.

Conclusions

CTBs limit Mφ NF‐κB activation and production of TNF‐α and MMP9 through an as‐yet unknown, cell‐to‐cell contact‐mediated mechanism. This suppression is distinct from the PGE2‐mediated Mφ TNF‐α suppression by DSC, suggesting that DSCs and CTBs regulate Mφ inflammation through distinct mechanisms. How Mφ integrates these signals in an intact GM will be paramount to determining causes and prevention of PPROM.
The association between congenital heart disease and small for gestational age with regard to the prevalence and outcomes
Authors: Ishikawa Takamichi , Uchiyama Hiroki , Baba Toru , Ohishi Akira , Iijima Shigeo , Iwashima Satoru
Published: September 2020

Aim

To evaluate the association between small for gestational age (SGA) and the prevalence of congenital heart disease (CHD) and the association of the SGA status with the outcomes among infants with CHD.

Methods

Echocardiography was performed within the first 5 days of life in 5664 consecutive infants. Infants were classified into four groups according to the presence or absence of SGA and CHD. All CHD infants were followed up until either spontaneous resolution of all cardiac lesions, invasive intervention or death. All newborns without CHD were followed for mortality until the final follow‐up date.

Results

A total of 303 infants were diagnosed with CHD, while 610 were diagnosed with SGA. Among the CHD infants, 56 were SGA, and 247 were not. A multivariable logistic regression analysis showed that the adjusted odds ratio of SGA (9.71, P < .001) was significantly higher than that of other parameters concerning predictors of invasive intervention or death. The mortality rate in the presence of both SGA and CHD (hazard ratio: 33.6, P < .001) was markedly higher than in the absence of both.

Conclusion

SGA was a significant predictor of invasive intervention for CHD. The combination of CHD and SGA carried a high risk of death beyond that of either alone.
Is the Death Penalty Debate Really Dead? Contrasting Capital Punishment Support in Canada and the United States
Authors: Rancourt Marc‐Antoine , Ouellet Catherine , Dufresne Yannick
Published: September 2020

For decades, capital punishment has been a highly divisive topic. Today, most democratic governments have done away with capital punishment, with few exceptions which include the United States. Drawing from the Canadian Election Study (2015) and the American National Election Study (2016), this article explores the underlying value systems that shape contemporary pro‐death penalty opinions in Canada and in the United States. Findings suggest that, in both countries, pro‐death penalty attitudes should be better understood as part of a “law and order syndrome.” In the United States, the distribution of attitudes toward death penalty is also the reflection of a partisan divide. Our results also support the hypothesis that government distrust increases death penalty support in Canada.
Apical pelvic organ prolapse repair via vaginal‐assisted natural orifice transluminal endoscopic surgery: Initial experience from a tertiary care hospital
Authors: Alay Ismail , Kaya Cihan , Cengiz Huseyin , Yildiz Sukru , Aslan Ozgur , Yasar Levent , Ekin Murat
Published: September 2020

Introduction

Natural orifice transluminal endoscopic surgery has been used for gynecologic operations in recent years. The aim of the study is to describe our initial experience using vaginal‐assisted natural orifice transluminal endoscopic surgery (vNOTES) for apical pelvic organ prolapse repair.

Methods

After patients underwent vaginal hysterectomy, vNOTES sacrocolpopexy (n = 4) or vNOTES high uterosacral ligament suspension (n = 7) were performed to treat symptomatic apical pelvic organ prolapse. Sociodemographic and clinical characteristics, Pelvic Organ Prolapse Quantification results, and recorded surgical data (eg, duration of surgery, intraoperative complications, additional prolapse and incontinence surgeries) were obtained from patient files and the hospital's database. Information from postoperative follow‐up visits, including complications and anatomical results, were also recorded.

Results

The mean age of the patients was 60.7 ± 9.1 years. The mean total operative time was 121.3 ± 22.7 minutes. The mean operative time for vaginal hysterectomy, vNOTES sacrocolpopexy, and vNOTES uterosacral ligament suspension was 46 ± 11.9, 65 ± 38, 25 ± 8.2 minutes, respectively. There were no intraoperative and postoperative complications observed. The mean postoperative 24‐hour visual analog scale score was 3.5 ± 1.9 for vNOTES sacrocolpopexy patients and 3.2 ± 0.9 for vNOTES uterosacral ligament suspension patients. Only one patient in the vNOTES sacrocolpopexy group had a recurrence; she experienced stage 2 anterior compartment prolapse 8 months after surgery.

Conclusion

As a treatment for apical pelvic organ prolapse, vNOTES is a feasible approach in both sacrocolpopexy and uterosacral ligament suspension.
Net benefit index: Assessing the influence of a biomarker for individualized treatment rules
Authors: Zhou Yiwang , Song Peter X.K. , Fu Haoda
Published: September 2020

One central task in precision medicine is to establish individualized treatment rules (ITRs) for patients with heterogeneous responses to different therapies. Motivated from a randomized clinical trial for Type 2 diabetic patients on a comparison of two drugs, that is, pioglitazone and gliclazide, we consider a problem: utilizing promising candidate biomarkers to improve an existing ITR. This calls for a biomarker evaluation procedure that enables to gauge added values of individual biomarkers. We propose an assessment analytic, termed as net benefit index (NBI), that quantifies a contrast between the resulting gain and loss of treatment benefits when a biomarker enters ITR to reallocate patients in treatments. We optimize reallocation schemes via outcome weighted learning (OWL), from which the optimal treatment group labels are generated by weighted support vector machine (SVM). To account for sampling uncertainty in assessing a biomarker, we propose an NBI‐based test for a significant improvement over the existing ITR, where the empirical null distribution is constructed via the method of stratified permutation by treatment arms. Applying NBI to the motivating diabetes trial, we found that baseline fasting insulin is an important biomarker that leads to an improvement over an existing ITR based only on patient's baseline fasting plasma glucose (FPG), age, and body mass index (BMI) to reduce FPG over a period of 52 weeks.
Child mortality estimation incorporating summary birth history data
Authors: Wilson Katie , Wakefield Jon
Published: September 2020

The United Nations' Sustainable Development Goal 3.2 aims to reduce under‐five child mortality to 25 deaths per 1000 live births by 2030. Child mortality tends to be concentrated in developing regions where information needed to assess achievement of this goal often comes from surveys and censuses. In both, women are asked about their birth histories, but with varying degrees of detail. Full birth history (FBH) data contain the reported dates of births and deaths of every surveyed mother's children. In contrast, summary birth history (SBH) data contain only the total number of children born and total number of children who died for each mother. Specialized methods are needed to accommodate this type of data into analyses of child mortality trends. We develop a data augmentation scheme within a Bayesian framework where for SBH data, birth and death dates are introduced as auxiliary variables. Since we specify a full probability model for the data, many of the well‐known biases that exist in this data can be accommodated, along with space‐time smoothing on the underlying mortality rates. We illustrate our approach in a simulation, showing robustness to model misspecification and that uncertainty is reduced when incorporating SBH data over simply analyzing all available FBH data. We also apply our approach to data from the Central region of Malawi and compare with the well‐known Brass method.
The Function of Work on the Countertransference in a Case with Constricted Discourse and Autistic Features
Authors: O'Neill Sylvia
Published: September 2020

This paper discusses the psychotherapy of a patient with autistic features and rigid resistance to free association. The patient often presented his experience as merely physical sensations. The paper juxtaposes two theories that illuminate the clinical picture. Tustin's theory of autistic objects identifies a defensive manoeuvre whereby sensation is actively substituted for the primary maternal object. Green's concept of the central phobic position describes a peculiarly rigid phobia of free association that functions to defend against awareness that a murder is felt to have taken place in the psyche. The author proposes that, in this patient, Tustin's substitution of sensation for the mother is Green's psychic murder. A therapeutic impasse that arose during the treatment was resolved following some working through in the countertransference. The patient's inability to free associate was subsequently ameliorated, and his previous inability to acknowledge oedipal reality shifted. He could then acknowledge, appreciate and identify with a paternal authority figure. This illustrates, the author considers, Scariati's observation that in the treatment of patients with impaired capacity for symbolization, countertransferential working through precedes the patient's acquiring a capacity for working through in the transference. Indeed, it facilitates this capacity.
The Early Ontogeny of Reason Giving
Authors: Köymen Bahar , Tomasello Michael
Published: September 2020

The key context within which preschool children learn to justify beliefs with reasons is collaborative problem‐solving and decision‐making with peers, including in the moral domain, in which they engage with another coequal mind in a cooperative spirit. Evidence for this proposal comes from recent studies in which children demonstrated sensitivity to the common ground assumptions they shared with their peer partners in decision‐making, as well as an ability to provide reasons relevant to their shared understanding. Training studies suggest that discourse with others about reasons for beliefs provides children with the appropriate learning experiences. Internalizing this communicative process may be crucial for individual deliberative reasoning.
Global protected‐area coverage and human pressure on tidal flats
Authors: Hill Narelle K. , Woodworth Bradley K. , Phinn Stuart R. , Murray Nicholas J. , Fuller Richard A.
Published: September 2020

Tidal flats are a globally distributed coastal ecosystem important for supporting biodiversity and ecosystem services. Local to continental‐scale studies have documented rapid loss of tidal habitat driven by human impacts, but assessments of progress in their conservation are lacking. With an internally consistent estimate of distribution and change, based on Landsat satellite imagery, now available for the world's tidal flats, we examined tidal flat representation in protected areas (PAs) and human pressure on tidal flats. We determined tidal flat representation and its net change in PAs by spatially overlaying tidal flat maps with the World Database of Protected Areas. Similarly, we overlaid the most recent distribution map of tidal flats (2014–2016) with the human modification map (HMc) (range from 0, no human pressure, to 1, very high human pressure) to estimate the human pressure exerted on this ecosystem. Sixty‐eight percent of the current extent of tidal flats is subject to moderate to very high human pressure (HMc > 0.1), but 31% of tidal flat extent occurred in PAs, far exceeding PA coverage of the marine (6%) and terrestrial (13%) realms. Net change of tidal flat extent inside PAs was similar to tidal flat net change outside PAs from 1999 to 2016. Substantial shortfalls in protection of tidal flats occurred across Asia, where large intertidal extents coincided with high to very high human pressure (HMc > 0.4–1.0) and net tidal flat losses up to 86.4 km² (95% CI 83.9–89.0) occurred inside individual PAs in the study period. Taken together, our results show substantial progress in PA designation for tidal flats globally, but that PA status alone does not prevent all habitat loss. Safeguarding the world's tidal flats will thus require deeper understanding of the factors that govern their dynamics and effective policy that promotes holistic coastal and catchment management strategies.
Liver transplantation for combined hepatocellular‐cholangiocarcinoma: Outcomes and prognostic factors for mortality. A multicenter analysis
Authors: Jaradat Derar , Bagias Georgios , Lorf Thomas , Tokat Yaman , Obed Aiman , Oezcelik Arzu
Published: September 2020

Introduction

Combined hepatocellular‐cholangiocarcinoma is rare and comprises features of hepatocellular carcinoma and cholangiocarcinoma. The treatment of choice has not yet been defined. The aim of the study was to analyze outcomes of patients with combined hepatocellular‐cholangiocarcinoma, who underwent liver transplantation.

Material and Methods

All patients with combined hepatocellular‐cholangiocarcinoma, who underwent liver transplantation, from January 2001 to August 2018 were identified. Pre‐, intra‐ and postoperative data were retrospectively assessed. A univariate analysis was performed to identify prognostic factors.

Results

A total number of 19 patients were included to this study. Perioperative death was seen in two patients (10.5%). Recurrent disease was reported in 11 patients (64.7%) within the median time of 4 months. One and three years survival rates were 57.1% (CI 0.301–1) and 38.1% (CI 0.137–1). Factors associated mortality were tumor size >3 cm, presence of lymphatic invasion, and prolonged ICU stay. Patients with mixed HCC‐CC lesions have significantly better survival compared to patients with separate lesions of HCC and CCC in one liver (p = .025).

Conclusion

Although overall survival rates are clearly decreased compared to HCC patients, liver transplantation should be taken under consideration for selected patients with early stage and real mixed HCC‐CC, who are likely to benefit from liver transplantation.
Risk factors for early development of cardiac allograft vasculopathy by intravascular ultrasound
Authors: Moayedi Yasbanoo , Fan Chun Po S. , Tremblay-Gravel Maxime , Miller Robert J. H. , Kawana Matsaka , Henricksen Erik , Parizo Justin , Wainwright Rebecca , Fearon William F. , Ross Heather J. , Khush Kiran K. , Teuteberg Jeffrey J.
Published: September 2020

Background

Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss. While there are numerous post‐transplant factors which may increase the risk of the development of CAV, there is a paucity of data on the impact of donor‐derived atherosclerosis (DA), early discontinuation of prednisone, and early initiation of proliferation signal inhibitors (PSI) as assessed by intravascular ultrasound (IVUS).

Methods

Retrospective single‐center study of all adult transplant patients (2008‐2017) with serial IVUS at baseline and annually for 5 years. DA was defined as a baseline maximal intimal thickness (MIT) ≥0.5 mm, and CAV development was defined as MIT ≥1 mm or an increase in MIT ≥0.5 mm at year 1 compared with baseline or an increase in 0.3 mm annually thereafter. Clinical risk factors for CAV were identified using multivariable hazard regression. Separate multistate models were applied to assess the association of prednisone discontinuation and PSI initiation and CAV.

Results

Of 282 patients screened, 186 patients had a 1‐year angiogram. The mean age of those included in the cohort was 51 ± 11 years, 70% were male, 58% were Caucasian, and 27% were supported by a left ventricular assist device. Donor atherosclerosis was present in 40%. The cumulative incidence of CAV at 5 years is 41% in DA‐ vs. 59% in DA + (p = .012). Donor age was a strong predictor of DA (p = .016). Significant risk factors for CAV included male sex (HR = 4.141, p = .001), non‐Caucasian race (HR = 1.98, p = .011), BMI < 18 kg/m2 (HR = 4.596, p = .042), longer ischemic time (HR = 1.374, p = .028), older donor age (HR = 1.158, p = .009), and rejection with hemodynamic compromise within the first year (HR = 2.858, p = .043). Prednisone discontinuation within 1 year was associated with a lower risk of CAV (HR 0.58 p = .047). Initiation of proliferation signal inhibitors (PSI) within 2 years resulted in fewer cases of CAV (HR 0.397 p < .001).

Conclusion

In patients with an angiogram at 1 year, those with DA were significantly more likely to develop CAV. Lower incidence of CAV by IVUS was seen in patients who discontinued prednisone in the first year or had initiation of a PSI within two years of transplantation. Knowledge of early IVUS may allow a more tailored approach to patient management.
What is Thy3a? A study of 336 Thy3a (AUS/FLUS) thyroid FNAs with histology compares UK RCPath with other reporting systems and shows how Thy3a subclassification can improve risk stratification and help address overuse of this category
Authors: van der Horst Cynthia , Wright Sylvia , Young David , Tailor Hitesh , Clark Louise
Published: September 2020

Introduction

Thy3a (AUS/FLUS) is an indeterminate and heterogeneous category in thyroid cytology. Thy3a reporting rates vary widely, with many laboratories documenting overuse. Subclassification of Thy3a helps with risk stratification. We aimed to investigate whether subclassification can also help address Thy3a overuse. We compare the UK reporting system with other terminologies.

Methods

An audit of thyroid fine needle aspirations (FNAs) reported at our institution between 2012 and 2017 was performed. Thy3a FNAs followed by histology were reviewed and subcategorised into four subgroups: Scanty Atypia (SA), Scanty Microfollicular (SMF), Favour Benign (FB) and Thyroiditis versus Neoplasm (TVN). Review and subclassification were blinded to histology outcomes. FNAs were correlated with histology and statistical analysis was performed.

Results

Our Thy3a rate was high (24% of all thyroid FNAs). For 336 Thy3a FNAs with histology, the malignancy rates of the four subgroups were: SA 68%, SMF 20%, FB 4%, TVN 31%. There were significant associations between subgroup and malignancy risk, and between subgroup and tumour risk. On histology, SA had more malignancies than expected and FB had fewer. SA and SMF had more tumours than expected and FB had fewer. SMF and Thy3f FNAs were similar in terms of tumour and malignancy outcomes.

Conclusions

Subclassification of Thy3a FNAs into these four subgroups is recommended. This can improve risk stratification and help address overuse of Thy3a. We propose that some FB and SMF cases could be safely diverted to Thy2 and Thy3f respectively. We compare various reporting terminologies and question how indeterminate FNAs should be classified.
Differential diagnosis of progressive intellectual and neurological deterioration in children
Authors: Verity Christopher , Baker Elaine , Maunder Polly , Pal Suvankar , Winstone Anne Marie
Published: September 2020

Aim

To report the differential diagnosis in children with progressive intellectual and neurological deterioration (PIND) in the UK.

Method

Since 1997 the PIND Study has searched for variant Creutzfeldt‐Jakob disease (vCJD) in children, using the British Paediatric Surveillance Unit to perform prospective surveillance of those younger than 16 years with PIND.

Results

From May 1997 to October 2019, 2255 children meeting PIND criteria had been notified, of whom 2008 (1085 males, 923 females) had underlying diagnoses. There were over 220 different diseases, including six cases of vCJD. The numbers presenting in four age groups were: <1 year, 805 (40%); 1 to 4 years inclusive, 825 (41%); 5 to 9 years inclusive, 264 (13%); and 10 to 15 years inclusive, 114 (6%). The two largest ethnic groups were White and Pakistani (58.2% and 17% of diagnosed cases). The most common diseases in these two ethnic groups are shown for the four age groups. The distribution of diseases varied with age but was quite similar in White and Pakistani children.

Interpretation

This paper provides a unique guide to the complex differential diagnosis of childhood PIND, showing considerable differences between four age groups, but similarities between ethnic groups. The PIND Study still provides the only systematic surveillance for vCJD in children in the UK.

What this paper adds

The prevalence of diseases causing childhood progressive intellectual and neurological deterioration in the UK is low (approximately 0.1/1000 live births).

There were more than 220 different disorders, mainly genetically determined.

The majority of disorders presented early in childhood: 81% before the age of 5 years.

There were similarities in the disease spectrum in White and Pakistani children.
Decision‐Making: The Process Is the Content in an Experience‐Based Classroom
Authors: Conklin Thomas A. , Boulamatsi Artemis
Published: September 2020

This article describes a multistep exercise focused on decision‐making that can be used in a variety of disciplines. The exercise helps students understand process issues in decision‐making and the complexity of doing so in real world scenarios. The exercise uses a case to illustrate the paradoxical effect of how decision‐makers often focus on the content of decisions in lieu of attending to the decision‐making process. It is best suited for upper‐level undergraduate and graduate students. Insights about process issues are revealed through creating a team contract, a team inventory, and making the decisions required in the case analysis. These revelations occur across three 75‐minute classes but can be adapted to the time available and relevance of the course. The article's structure is organized according to Wiggins and McTighe's curriculum development model.
Effects of visual adaptation on orientation selectivity in cat secondary visual cortex
Authors: Lussiez Rudy , Chanauria Nayan , Ouelhazi Afef , Molotchnikoff Stéphane
Published: September 2020

Neuron orientation selectivity, otherwise known as the ability to respond optimally to a preferred orientation, has been extensively described in both primary and secondary visual cortices. This orientation selectivity, conserved through all cortical layers of a given column, is the primary basis for cortical organization and functional network emergence. While this selectivity is programmed and acquired since critical period, it has always been believed that in a mature brain, neurons’ inherent functional features could not be changed. However, a plurality of studies has investigated the mature brain plasticity in V1, by changing the cells’ orientation selectivity with visual adaptation. Using electrophysiological data in both V1 and V2 areas, this study aims to investigate the effects of adaptation on simultaneously recorded cells in both areas. Visual adaptation had an enhanced effect on V2 units, as they exhibited greater tuning curve shifts and a more pronounced decrease of their OSI. Not only did adaptation have a different effect on V2 neurons, it also elicited a different response depending on the neuron's cortical depth. Indeed, in V2, cells in layers II‐III were more affected by visual adaptation, while infragranular layer V units exhibited little to no effect at all.
Is the medicine right?
Authors: Meloni Gabriella
Published: September 2020

Is asking the Better Regulation Agenda (BRA) to answer the same preconditions it requires for any regulatory action a proper treatment? Does any assessment of the agenda necessarily imply a thorough definition of the costs and the benefits deriving from its application or is it enough to provide a few key insights to perform it? Is the BRA really so ideological, deriving from “a liberal analytical framework that considers no regulation/state intervention” as the preferred option? Is regulatory quality an issue that “cannot realistically be solved”? Does the principle of subsidiarity as a policy objective need some revision? Several questions come to mind when reading a very thought‐provoking article that is very critical of the BRA but that in the end recognises some of its main qualities.
Cropland connectivity affects genetic divergence of Colorado potato beetle along an invasion front
Authors: Yang Fangyuan , Liu Ning , Crossley Michael S. , Wang Pengcheng , Ma Zhuo , Guo Jianjun , Zhang Runzhi
Published: September 2020

The population genetic structure of invasive species can be strongly affected by environmental and landscape barriers to dispersal. Disentangling the relative contributions of these factors to genetic divergence among invading populations is a fundamental goal of landscape genetics with important implications for invasion management. Here, we relate patterns of genetic divergence in a global invasive agricultural pest, Colorado potato beetle (CPB; Leptinotarsa decemlineata), to environmental and landscape factors along an invasion front in Northwestern China. We first used microsatellite markers and spatial‐temporal samples to assess broad patterns of genetic diversity as well as fine‐scale changes in patterns of genetic divergence. We then distinguished the relative contributions of five factors to genetic divergence among front populations: geographic distance (isolation by distance), climate dissimilarity (isolation by environment), and least‐cost distances (isolation by resistance) modeled with three factors: climate suitability, cropland cover, and road networks. Genetic diversity broadly decreased from West to East, with the exception being Eastern China. Low levels of genetic diversity and varying degrees of divergence were observed in Northwestern China, reflecting the potential effect of landscape heterogeneity. Least‐cost distance across cropland cover was most positively correlated with genetic divergence, suggesting a role of croplands in facilitating gene flow. The contribution of climate to genetic divergence was secondary, whether modeled in terms of local adaptability or connectivity of the climatic landscape, suggesting that constraints to CPB gene flow imposed by a harsh climate may be ameliorated in agricultural landscapes. No evidence was found for an obvious effect of road networks on genetic divergence and population structuring. Our study provides an example of how agricultural landscape connectivity can facilitate the spread of invasive pests, even across a broad climatic gradient. More broadly, our findings can guide decisions about future land management for mitigating further spread.
Prolyl and lysyl hydroxylases in collagen synthesis
Authors: Salo Antti M. , Myllyharju Johanna
Published: September 2020

Collagens are the most abundant proteins in the extracellular matrix. They provide a framework to build organs and tissues and give structural support to make them resistant to mechanical load and forces. Several intra‐ and extracellular modifications are needed to make functional collagen molecules, intracellular post‐translational modifications of proline and lysine residues having key roles in this. In this article, we provide a review on the enzymes responsible for the proline and lysine modifications, that is collagen prolyl 4‐hydroxylases, 3‐hydroxylases and lysyl hydroxylases, and discuss their biological functions and involvement in diseases.
Marriage as Gatekeeper: The Misguided Reliance on Marital Status Criteria to Determine Third‐Party Standing†
Authors: Atwood Barbara A.
Published: September 2020

This essay examines the continued use of parental marital status as a gatekeeper to determine third‐party standing. Under the statutory law of about half the states, nonparents lack standing to seek contact with a child over parental objection if the child's parents are in an intact marriage. A typical statutory framework grants access to court only if a parent has died or the parents are divorced or never married. While such a framework may have intuitive appeal, case law reveals the illogical results it can produce. Moreover, the framework defines parental liberty based on marital status – an approach in tension, if not in direct conflict, with Troxel. At the same time, the framework disserves children's interests by ignoring their established relationships with third parties in determining standing. Alternative approaches proposed by the Uniform Law Commission and the American Law Institute, which impose a heightened burden of proof and require a showing of harm to the child if contact is denied, would give parental liberty a more even‐handed deference while also respecting the importance of children's established bonds.
COVID‐19 in Australia: Impacts on Separated Families, Family Law Professionals, and Family Courts
Authors: Smyth Bruce M. , Moloney Lawrence J. , Brady Jacqueline M. , Harman Judge Joe , Esler Marian
Published: September 2020

Around the globe, many families are experiencing significant anxieties linked to COVID‐19. These include health concerns and economic pressures, both of which are frequently taking place against a backdrop of various levels of social isolation. In addition, many parents have been juggling home schooling requirements in the face of radically different work arrangements including the loss of employment altogether. Unsurprisingly, additional challenges and stresses are emerging for separated families, family law professionals, and family courts. In this article – written at a point‐in‐time in a rapidly evolving COVID‐19 context – we reflect on key challenges for separated families in Australia, and some of the emerging professional responses.