bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential biomarkers for neuroinflammation and neurodegeneration at short and long term after neonatal hypoxic-ischemic insult in rat
Authors: Borjini Nozha , Sivilia Sandra , Giuliani Alessandro , Fernandez Mercedes , Giardino Luciana , Facchinetti Fabrizio , Calzà Laura
Published: October 2019

Background

Hypoxic-ischemic (HI) encephalopathy causes life-long morbidity and premature mortality in term neonates. Therapies in addition to whole-body cooling are under development to treat the neonate at risk for HI encephalopathy, but are not a quickly measured serum inflammatory or neuronal biomarkers to rapidly and accurately identify brain injury in order to follow the efficacy of therapies.

Methods

In order to identify potential biomarkers for early inflammatory and neurodegenerative events after neonatal hypoxia-ischemia, both male and female Wistar rat pups at postnatal day 7 (P7) were used and had their right carotid artery permanently doubly occluded and exposed to 8% oxygen for 90 min. Sensory and cognitive parameters were assessed by open field, rotarod, CatWalk, and Morris water maze (MWM) test. Plasma and CSF biomarkers were investigated on the acute (24 h and 72 h) and chronic phase (4 weeks). Brains were assessed for gene expression analysis by quantitative RT-PCR Array.

Results

We found a delay of neurological reflex maturation in HI rats. We observed anxiolytic-like baseline behavior in males more than females following HI injury. HI rats held on the rotarod for a shorter time comparing to sham. HI injury impaired spatial learning ability on MWM test. The CatWalk assessment demonstrated a long-term deficit in gait parameters related to the hind paw. Proinflammatory biomarkers such as IL-6 in plasma and CCL2 and TNF-α in CSF showed an upregulation at 24 h after HI while other cytokines, such as IL-17A and CCL5, were upregulated after 72 h in CSF. At 24 h post-injury, we observed an increase of Edn1, Hif1-α, and Mmp9 mRNA levels in the ipsilateral vs the contralateral hemisphere of HI rats. An upregulation of genes involved with clotting and hematopoietic processes was observed 72 h post-injury.

Conclusions

Our work showed that, in the immature brain, the HI injury induced an early increased production of several proinflammatory mediators detectable in plasma and CSF, followed by tissue damage in the hypoxic hemisphere and short-term as well as long-lasting neurobehavioral deficits.
Role of chemical composition and redox modification of poorly soluble nanomaterials on their ability to enhance allergic airway sensitisation in mice
Authors: Dekkers Susan , Wagner James G. , Vandebriel Rob J. , Eldridge Elyse A. , Tang Selina V. Y. , Miller Mark R. , Römer Isabella , de Jong Wim H. , Harkema Jack R. , Cassee Flemming R.
Published: October 2019

Background

Engineered nanoparticles (NPs) have been shown to enhance allergic airways disease in mice. However, the influence of the different physicochemical properties of these particles on their adjuvant properties is largely unknown. Here we investigate the effects of chemical composition and redox activity of poorly soluble NPs on their adjuvant potency in a mouse model of airway hypersensitivity.

Results

NPs of roughly similar sizes with different chemical composition and redox activity, including CeO2, Zr-doped CeO2, Co3O4, Fe-doped Co3O4(using Fe2O3 or Fe3O4) and TiO2 NPs, all showed adjuvant activity. OVA induced immune responses following intranasal exposure of BALB/c mice to 0.02% OVA in combination with 200 μg NPs during sensitization (on day 1, 3, 6 and 8) and 0.5% OVA only during challenge (day 22, 23 and 24) were more pronounced compared to the same OVA treatment regime without NPs. Changes in OVA-specific IgE and IgG1 plasma levels, differential cell count and cytokines in bronchoalveolar lavage fluid (BALF), and histopathological detection of mucosa cell metaplasia and eosinophil density in the conducting airways were observed. Adjuvant activity of the CeO2 NPs was primarily mediated via the Th2 response, while that of the Co3O4 NPs was characterised by no or less marked increases in IgE plasma levels, BALF IL-4 and IL-5 concentrations and percentages of eosinophils in BALF and more pronounced increases in BALF IL-6 concentrations and percentages of lymphocytes in BALF. Co-exposure to Co3O4 NPs with OVA and subsequent OVA challenge also induced perivascular and peribronchiolar lymphoid cell accumulation and formation of ectopic lymphoid tissue in lungs. Responses to OVA combined with various NPs were not affected by the amount of doping or redox activity of the NPs.

Conclusions

The findings indicate that chemical composition of NPs influences both the relative potency of NPs to exacerbate allergic airway sensitization and the type of immune response. However, no relation between the acellular redox activity and the observed adjuvant activity of the different NPs was found. Further research is needed to pinpoint the precise physiological properties of NPs and biological mechanisms determining adjuvant activity in order to facilitate a safe-by-design approach to NP development.
Morbidity and mortality of serious gastrointestinal complications after lung transplantation
Authors: Zevallos-Villegas Annette , Alonso-Moralejo Rodrigo , Cambra Félix , Hermida-Anchuelo Ana , Pérez-González Virginia , Gámez-García Pablo , Sayas-Catalán Javier , De Pablo- Gafas Alicia
Published: October 2019

Background

Gastrointestinal complications after lung transplatation are associated with an increased risk of morbidity and mortality. This study aims to describe severe gastrointestinal complications (SGC) after lung transplantation.

Methods

We performed a prospective, observational study that included 136 lung transplant patients during a seven year period in a tertiary care universitary hospital. SGC were defined as any diagnosis related to the gastrointestinal or biliary tract leading to lower survival rates or an invasive therapeutic procedure. Early and late complications were defined as those occurring < 30 days and ≥ 30 days post-transplant. The survival function was calculated through the Kaplan-Meier estimator. Variables were analyzed using univariate and multivariate analysis. Statistical significance was defined as p < 0.05.

Results

There were 17 (12.5%) SGC in 17 patients. Five were defined as early. Twelve patients (70.6%) required surgical treatment. Mortality was 52.9% (n = 9). Patients with SGC had a lower overall survival rate compared to those who did not (14 vs 28 months, p = 0.0099). The development of arrhythmias in the first 48 h of transplantation was a risk factor for gastrointestinal complications (p = 0.0326).

Conclusions

SGC are common after lung transplantation and are associated with a considerable increase in morbidity-mortality. Early recognition is necessary to avoid delays in treatment, since a clear predictor has not been found in order to forecast this relevant comorbidity.
Growth characteristics and therapeutic decision markers in von Hippel-Lindau disease patients with renal cell carcinoma
Authors: Schuhmacher Patrick , Kim Emily , Hahn Felix , Sekula Peggy , Jilg Cordula Annette , Leiber Christian , Neumann Hartmut P. , Schultze-Seemann Wolfgang , Walz Gerd , Zschiedrich Stefan
Published: October 2019

Background

Von Hippel-Lindau (VHL) disease is a multi-systemic hereditary disease associated with several benign and malignant tumor entities, including clear cell renal cell carcinoma (ccRCC). Since ccRCCs grow slowly, nephron sparing surgery is typically performed at a tumor diameter of 3–4 cm before the tumor metastasizes. However, in the case of recurrent disease, repeated surgical intervention can impair renal function. Therefore, it is crucial to optimize the timing for surgical interventions through a better understanding of the growth kinetics of ccRCCs in VHL. We investigated tumor growth kinetics and modern volumetric assessment to guide future therapeutic decisions.

Results

The prevalence of ccRCC was 28% in a cohort of 510 VHL patients. Of 144 patients with ccRCC, 41 were followed with serial imaging which identified 102 renal tumors, which exhibited heterogeneous growth kinetics. ccRCCs grew at an average absolute growth rate of 0.287 cm/year, an average relative growth rate [(lnV1-lnV0)/(t1-t0)] of 0.42% and an average volume doubling time of 27.15 months. Women had a faster relative growth rate than men. Age and specific mutations did not influence tumor growth. Because of the tumor heterogeneity, we developed an additional cut-off volume of 40 cm3 for surgical intervention.

Conclusions

Tumor heterogeneity and differences in growth kinetics is suggestive of a state of transient tumor dormancy in ccRCCs of VHL patients. The relative growth rate has not been previously described in other studies. Volumetric assessment as an additional parameter for surgical intervention could be a useful clinical tool and needs further investigation.
Reducing research waste by promoting informed responses to invitations to participate in clinical trials
Authors: Gillies Katie , Chalmers Iain , Glasziou Paul , Elbourne Diana , Elliott Jim , Treweek Shaun
Published: October 2019

Poor recruitment to, and retention in, clinical trials is a source of research waste that could be reduced by more informed choices about participation. Barriers to effective recruitment and retention can be wide-ranging but relevance of the questions being addressed by trials and the outcomes that they are assessing are key for potential participants. Decisions about trial participation should be informed by general and trial-specific information and by considering broader assessments of ‘informedness’ and how they impact on both recruitment and retention. We suggest that more informed decisions about trial participation should encourage personally appropriate decisions, increase recruitment and retention, and reduce research waste and increase its value.
Outcome in juvenile idiopathic arthritis: a population-based study from Sweden
Authors: Berthold Elisabet , Månsson Bengt , Kahn Robin
Published: October 2019

Background

As the treatment arsenal for children with juvenile idiopathic arthritis (JIA) has expanded during the last decades, follow-up studies are needed on children diagnosed in the era of biological treatment to evaluate if this has improved the outcome. Our aim was to study the epidemiology and outcome of JIA in southern Sweden using a population-based cohort of children with a validated diagnosis of JIA collected over 9 years.

Methods

Potential cases of JIA between 2002 and 2010 were collected after a database search, using the ICD codes M08-M09. The study area was Skåne, the southernmost county of Sweden (population 1.24 million; 17.6% aged < 16 years). The JIA diagnosis was validated and subcategorized through medical record review based on the criteria defined by the International League of Associations for Rheumatism (ILAR). Parameters on disease activity and pharmacologic treatment were recorded annually until the end of the study period (December 31, 2015).

Results

In total, 251 cases of JIA were confirmed. The mean annual incidence rate for JIA was estimated to be 12.8/100,000 children < 16 years, with the highest age-specific annual incidence at the age of 2 years (36/100,000). Oligoarthritis was the largest subgroup (44.7%), and systemic JIA was the smallest subgroup (2.8%). Methotrexate was the most common disease-modifying anti-rheumatic drug prescribed (60.6%). Tumor necrosis factor alpha inhibitors were used as treatment for 23.9% of the children. Only 40.0% of the follow-up years, with a median follow-up time of 8 years, were free of arthritis or uveitis. Uveitis occurred in 10.8% of the children (8.0% chronic uveitis), and the need for joint corrective orthopedic surgery was 9.2%.

Conclusions

The incidence of JIA in this well-defined, population-based cohort is slightly lower than in previously published studies from Scandinavia. The need for orthopedic surgery and the presence of uveitis are diminished compared to studies with patients diagnosed more than 20 years ago. Children with JIA however still experience disease activity more than 50% of the time. In conclusion, we still have long-term challenges in the care for children with JIA, in spite of state-of-the-art treatment.
Patient advocacy organizations’ information for patients on pre-approval access to investigational treatments
Authors: Folkers Kelly McBride , Leone Sarah , Caplan Arthur
Published: October 2019

Objective

To evaluate the availability of information regarding patient access to investigational treatments through clinical trials and non-trial pre-approval access pathways from a sample of patient advocacy organization (PAO) websites in the United States.

Results

We systematically analyzed the content of 118 randomly selected PAO websites to assess whether they contained information on clinical trials and non-trial pathways—e.g., the U.S. Food and Drug Administration (FDA) expanded access (EA) program and right to try—over the course of two months from February to March 2019. A majority (81%, n = 96) of PAOs provided a link to ClinicalTrials.gov, and 73% (n = 86) had their own clinical trial finder or list of relevant trials. 23% (n = 27) mentioned EA, with 8% (n = 9) providing specific resources for FDA’s EA program. 8% (n = 10) provided a statement on the passage of the federal right to try law. A majority of PAO websites contained information on clinical trials, but a minority discussed non-trial pre-approval access. The lack of information on the latter highlights an area in need of improvement.
Prevalence of intestinal parasitic infections in Hawassa University students’ clinic, Southern Ethiopia: a 10-year retrospective study
Authors: Menjetta Tadesse , Simion Teketel , Anjulo Wondimu , Ayele Kidist , Haile Mekides , Tafesse Tewodros , Asnake Solomon
Published: October 2019

Objective

The purpose of this study was to determine the prevalence of intestinal parasitic infections among patients who had attended Hawassa University students’ clinic, Southern Ethiopia.

Result

Over the 10 years period, a total of 13,679 patients visiting Hawassa University students’ clinic were included in the study. A total of 6553 (47.9%) patients were positive for at least one intestinal parasite. The overall prevalence of intestinal helminth and protozoan infections was 20.3% and 27.6% respectively. There were four dual infections and one triple infection. E. histolytica/E. dispar trophozoite was the most common identified parasite, which was seen in 18% of the patients while Enterobius vermicularis (0.1%) was the least reported parasite. Other parasites identified were Ascaris lumbricoides (15.0%), Hookworm species (2.0%), Taenia species (1.8%), Hymenolepis nana (0.7%), Strongyloides stercoralis (0.3%), Trichuris trichuria (0.2%), and Shistosoma mansoni (0.2%). The prevalence of helminthes was higher in females (23.3%) than in males (19.5%) (P < 0.00001) while that of protozoan infections was 28.5% in males than females (23.8%) (574/2414) (P < 0.00001).
Influence of pig gut microbiota on Mycoplasma hyopneumoniae susceptibility
Authors: Surendran Nair Meera , Eucker Tyson , Martinson Brian , Neubauer Axel , Victoria Joseph , Nicholson Bryon , Pieters Maria
Published: October 2019

This study investigated the influence of gut microbiome composition in modulating susceptibility toMycoplasma hyopneumoniaein pigs. Thirty-two conventionalM. hyopneumoniaefree piglets were randomly selected from six different litters at 3 weeks of age and were experimentally inoculated withM. hyopneumoniaeat 8 weeks of age. Lung lesion scores (LS) were recorded 4 weeks post-inoculation (12 weeks of age) from piglet lungs at necropsy. Fecal bacterial community composition of piglets at 3, 8 and 12 weeks of age were targeted by amplifying the V3–V4 region of the 16S rRNA gene. The LS ranged from 0.3 to 43% with an evident clustering of the scores observed in piglets within litters. There were significant differences in species richness and alpha diversity in fecal microbiomes among piglets within litters at different time points (p < 0.05). The dissimilarity matrices indicated that at 3 weeks of age, the fecal microbiota of piglets was more dissimilar compared to those from 8 to 12 weeks of age. Specific groups of bacteria in the gut that might predict the decreased severity ofM. hyopneumoniaeassociated lesions were identified. The microbial shift at 3 weeks of age was observed to be driven by the increase in abundance of the indicator family, Ruminococcaceae in piglets with low LS (p < 0.05). The taxa,Ruminococcus_2 having the highest richness scores, correlated significantly between litters showing stronger associations with the lowest LS (r = −0.49,p = 0.005). These findings suggest that early life gut microbiota can be a potential determinant forM. hyopneumoniaesusceptibility in pigs.
Risk of major bleeding during extended oral anticoagulation in patients with first unprovoked venous thromboembolism: a systematic review and meta-analysis protocol
Authors: Khan Faizan , Kimpton Miriam , Tritschler Tobias , Le Gal Grégoire , Hutton Brian , Fergusson Dean A. , Rodger Marc A.
Published: October 2019

Background

The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE.

Methods

Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis.

Discussion

The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE.

Systematic review registration

PROSPERO CRD42019128597.
Histopathological and genetic changes proved the anti-cancer potential of free and nano-capsulated sinapic acid
Authors: Badr Doaa A. , Amer Mohamed E. , Abd-Elhay Wagih M. , Nasr Mohamed S. M. , Abuamara Tamer M. M. , Ali Harbi , Mohamed Aly F. , Youssef Maha A. , Awwad Nasser S. , Ju Yi-Hsu , Fazary Ahmed E.
Published: October 2019

Cancer is known to be a fierce disease that causes a large percentage of the deaths worldwide. The common cancer treatments; chemotherapy, radiotherapy and surgery are known for their severe side effects; therefore scientists are working on finding solutions to reduce these drawbacks. One of these treatment systems is the sustained released drugs formulations, these systems depend on the encapsulation of the chemotherapy within an emulsifying agent, in order to obtain a slow drug release of low doses over long time intervals. In this study, the anti-cancer effects of free and encapsulated sinapic acid was tested against lung (A549), and colon (CaCo2) cancer cell lines, along with normal fibroblast cells (HFB4) as a negative control. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed for IC50 evaluation, also cell cycle assay was performed to detect cell cycle arrest status and related anti-apoptotic and pro-apoptotic; Blc-2, BAX, and P53 gene profile fold changes post cellular treatment. Data recorded revealed that encapsulated SA showed a lower toxicity than the free form to both cell lines and also to the normal cells. The cell cycle analysis showed a cell cycle arrest at the G2/M phase post cell treatment with the free and encapsulated sinapic acid accompanied with up regulation of Bax and P53 and a down regulation of Blc-2 genes in both cell lines. The data suggest a promising anti-cancer and anti-proliferative potential of free and encapsulated sinapic acid. Also they show that the anti-cancer effect of free and encapsulated sinapic acid is quite close.
Tropical cyclones alter short-term activity patterns of a coastal seabird
Authors: Wilkinson Bradley P. , Satgé Yvan G. , Lamb Juliet S. , Jodice Patrick G. R.
Published: October 2019

Background

Mobile organisms in marine environments are expected to modify their behavior in response to external stressors. Among environmental drivers of animal movement are long-term climatic indices influencing organism distribution and short-term meteorological events anticipated to alter acute movement behavior. However, few studies exist documenting the response of vagile species to meteorological anomalies in coastal and marine systems.

Methods

Here we examined the movements of Eastern brown pelicans (Pelecanus occidentalis carolinensis) in the South Atlantic Bight in response to the passage of three separate hurricane events in 2 years. Pelicans (n = 32) were tracked with GPS satellite transmitters from four colonies in coastal South Carolina, USA, for the entirety of at least one storm event. An Expectation Maximization binary Clustering algorithm was used to discretize pelican behavioral states, which were pooled into ‘active’ versus ‘inactive’ states. Multinomial logistic regression was used to assess behavioral state probabilities in relation to changes in barometric pressure and wind velocity.

Results

Individual pelicans were more likely to remain inactive during tropical cyclone passage compared to baseline conditions generally, although responses varied by hurricane. When inactive, pelicans tended to seek shelter using local geomorphological features along the coastline such as barrier islands and estuarine systems.

Conclusions

Our telemetry data showed that large subtropical seabirds such as pelicans may mitigate risk associated with spatially-extensive meteorological events by decreasing daily movements. Sheltering may be related to changes in barometric pressure and wind velocity, and represents a strategy common to several other classes of marine vertebrate predators for increasing survival probabilities.
Sarm1 deletion suppresses TDP-43-linked motor neuron degeneration and cortical spine loss
Authors: White Matthew A. , Lin Ziqiang , Kim Eugene , Henstridge Christopher M. , Pena Altamira Emiliano , Hunt Camille K. , Burchill Ella , Callaghan Isobel , Loreto Andrea , Brown-Wright Heledd , Mead Richard , Simmons Camilla , Cash Diana , Coleman Michael P. , Sreedharan Jemeen
Published: October 2019

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition that primarily affects the motor system and shares many features with frontotemporal dementia (FTD). Evidence suggests that ALS is a ‘dying-back’ disease, with peripheral denervation and axonal degeneration occurring before loss of motor neuron cell bodies. Distal to a nerve injury, a similar pattern of axonal degeneration can be seen, which is mediated by an active axon destruction mechanism called Wallerian degeneration. Sterile alpha and TIR motif-containing 1 (Sarm1) is a key gene in the Wallerian pathway and its deletion provides long-term protection against both Wallerian degeneration and Wallerian-like, non-injury induced axonopathy, a retrograde degenerative process that occurs in many neurodegenerative diseases where axonal transport is impaired. Here, we explored whether Sarm1 signalling could be a therapeutic target for ALS by deletingSarm1from a mouse model of ALS-FTD, a TDP-43Q331K, YFP-H double transgenic mouse.Sarm1deletion attenuated motor axon degeneration and neuromuscular junction denervation. Motor neuron cell bodies were also significantly protected. Deletion ofSarm1also attenuated loss of layer V pyramidal neuronal dendritic spines in the primary motor cortex. Structural MRI identified the entorhinal cortex as the most significantly atrophic region, and histological studies confirmed a greater loss of neurons in the entorhinal cortex than in the motor cortex, suggesting a prominent FTD-like pattern of neurodegeneration in this transgenic mouse model. Despite the reduction in neuronal degeneration,Sarm1deletion did not attenuate age-related behavioural deficits caused by TDP-43Q331K. However,Sarm1deletion was associated with a significant increase in the viability of male TDP-43Q331Kmice, suggesting a detrimental role of Wallerian-like pathways in the earliest stages of TDP-43Q331K-mediated neurodegeneration. Collectively, these results indicate that anti-SARM1 strategies have therapeutic potential in ALS-FTD.
Modelling clay materials used in artworks: an infrared spectroscopic investigation
Authors: Stuart B. H. , Thomas P. S. , Barrett M. , Head K.
Published: October 2019

Modelling clays are utilised by artists for their malleable properties. One of the challenges in managing collections containing such materials is the variety of commercial compositions available and, therefore, the variation in the requirements for storage and maintenance of such artefacts. The Art Gallery of New South Wales in Australia is responsible for the care of a range of artworks that contain modelling materials, some of which show detrimental property changes and there is concern for the longevity of such works. The aim of the current research is to determine the compositions of the modelling materials utilised in works produced by different artists in the gallery’s collection. Infrared spectroscopy was used to identify the main constituents of samples collected from the works of four different artists and a variety of material types were determined. Oil-based, air-hardening and polymer clays of varying composition were identified in the survey of artworks. Signs of deterioration in particular artworks were able to be characterised using spectroscopy, with the mechanisms identified including loss and oxidation of the oil component. Where a polymer clay was chosen by one artist, the distortion of the artwork was due to flow of the material over time and demonstrates the need for an understanding of the long term properties of the materials being used. The study has highlighted the need for conservators to have a detailed understanding of modelling materials to ensure the longevity of artworks containing this class of materials.
A fine-scale assessment of the ecosystem service-disservice dichotomy in the context of urban ecosystems affected by alien plant invasions
Authors: Potgieter Luke J. , Gaertner Mirijam , O’Farrell Patrick J. , Richardson David M.
Published: October 2019

Background

Natural resources within and around urban landscapes are under increasing pressure from ongoing urbanisation, and management efforts aimed at ensuring the sustainable provision of ecosystem services (ES) are an important response. Given the limited resources available for assessing urban ES in many cities, practical approaches for integrating ES in decision-making process are needed.

Methods

We apply remote sensing techniques (integrating LiDAR data with high-resolution multispectral imagery) and combined these with supplementary spatial data to develop a replicable approach for assessing the role of urban vegetation (including invasive alien plants) in providing ES and ecosystem disservices (EDS). We identify areas denoting potential management trade-offs based on the spatial distribution of ES and EDS using a local-scale case study in the city of Cape Town, South Africa. Situated within a global biodiversity hotspot, Cape Town must contend with widespread invasions of alien plants (especially trees and shrubs) along with complex socio-political challenges. This represents a useful system to examine the challenges in managing ES and EDS in the context of urban plant invasions.

Results

Areas of high ES provision (for example carbon sequestration, shade and visual amenity) are characterized by the presence of large trees. However, many of these areas also result in numerous EDS due to invasions of alien trees and shrubs – particularly along rivers, in wetlands and along the urban edge where tall alien trees have established and spread into the natural vegetation (for example increased water consumption, increased fire risk and reduced soil quality). This suggests significant trade-offs regarding the management of species and the ES and EDS they provide.

Conclusions

The approach applied here can be used to provide recommendations and to guide city planners and managers to fine-tune management interventions at local scales to maximise the provision of ES.
Citizenship acquisition of Turkish immigrants in Canada and Germany: a comparative analysis
Authors: Yetkin Aker Deniz
Published: October 2019

This study aims to shed light on how high-skilled and business Turkish immigrants (HSBTI) decide to acquire host country’s citizenship and why some of them choose not to seek naturalization. With this in mind, a comparative case study of Canada and Germany was designed. It is proposed that host country citizenship and migration policy, social, economic and political costs and benefits of host country’s citizenship and individuals’ conceptualization of citizenship impact the decision-making process of HSBTI. Based on the data results, the study argues that social, economic and political opportunities in host countries (such as the right to vote), multicultural migration and citizenship policies of those countries and valuing citizenship as a commodity positively influence the naturalization decisions of HSBTI interviewees, while restricted policies, economic costs of citizenship and seeing citizenship as a sense of belonging adversely affect their decisions.
Laparoscopic versus open pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a propensity score matching analysis
Authors: Zhou Wentao , Jin Weiwei , Wang Dansong , Lu Chao , Xu Xuefeng , Zhang Renchao , Kuang Tiantao , Zhou Yucheng , Wu Wenchuan , Jin Dayong , Mou Yiping , Lou Wenhui
Published: October 2019

Background

A growing body of evidence supports the use of laparoscopic pancreaticoduodenectomy (LPD) as an efficient and feasible surgical technique. However, few studies have investigated its applicability in pancreatic ductal adenocarcinoma (PDAC), and the long‐term efficacy of LPD on PDAC remains unclear. This study aimed to compare the short‐ and long‐term outcomes between LPD and open pancreaticoduodenectomy (OPD) for PDAC.

Methods

The data of patients who had OPD or LPD for PDAC between January 2013 and September 2017 were retrieved. Their postoperative outcomes and survival were compared after propensity score matching.

Results

A total of 309 patients were included. After a 2:1 matching, 93 cases in the OPD group and 55 in the LPD group were identified. Delayed gastric emptying (DGE), particularly grade B/C DGE, occurred less frequently in the LPD group than in the OPD group (1.8% vs. 36.6%, P < 0.001; 1.8% vs. 22.6%, P = 0.001). The overall complication rates were significantly lower in the LPD group than in the OPD group (49.1% vs. 71.0%, P = 0.008), whereas the rates of major complications were similar (10.9% vs. 14.0%, P = 0.590). In addition, the median overall survival was comparable between the two groups (20.0 vs. 18.7 months, P = 0.293).

Conclusion

LPD was found to be technically feasible with efficacy similar to OPD for patients with PDAC.
Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children’s Oncology Group
Authors:   for the Children’s Oncology Group, Kopp Lisa M. , Womer Richard B. , Schwartz Cindy L. , Ebb David H. , Franco Vivian I. , Hall David , Barkauskas Donald A. , Krailo Mark D. , Grier Holcombe E. , Meyers Paul A. , Wexler Leonard H. , Marina Neyssa M. , Janeway Katherine A. , Gorlick Richard , Bernstein Mark L. , Lipshultz Steven E.
Published: October 2019

Background

Dexrazoxane protects from lower-cumulative-dose doxorubicin cardiotoxicity, but the effect of dexrazoxane in children with sarcoma treated with higher-cumulative-dose doxorubicin is unknown.

Methods

We evaluated children with osteosarcoma (OS) on two Children’s Oncology Group trials with higher dose doxorubicin (375–600 mg/m2) preceded by dexrazoxane (10:1 dexrazoxane:doxorubicin dosing). They were evaluated after the minimum expected treatment time (METT), defined as 28 weeks. Cardiotoxicity was identified by echocardiography and serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Second malignant neoplasm (SMN) data was collected.

Results

All children had normal left ventricular (LV) systolic function as measured by LV fractional shortening and no heart failure. The end-diastolic septal thickness Z-scores (P < 0.01) and LV mass Z-scores (P < 0.01) were significantly smaller than normal for body-surface area in both sexes. The average LV mass Z-scores were significantly smaller for girls (P < 0.01) and marginally smaller for boys (P = 0.06). Girls had significantly smaller LV end-diastolic dimension Z-scores normalized to BSA (P < 0.01) compared to healthy controls and had significant increases in NT-proBNP. Four children developed SMNs as first events, a rate similar to historical controls.

Conclusions

Dexrazoxane prevented LV dysfunction and heart failure in children with OS receiving higher dose doxorubicin. However, LV structural changes were not fully prevented, especially in girls. As a result, hearts become abnormally small for body size, resulting in higher LV stress. Dexrazoxane did not increase the risk of SMN. Dexrazoxane should be used in this population, particularly for girls, to mitigate anthracycline-induced cardiotoxicity.

Trial registrations

ClinicalTrials.gov: NCT00003937 (P9754) registered 1 Nov 1999, and NCT00023998 (AOST0121) registered 13 Sept 2001.
Synthesis and analysis of separation processes for extracellular chemicals generated from microbial conversions
Authors: Wu Wenzhao , Yenkie Kirti M , Maravelias Christos T.
Published: October 2019

Recent advances in metabolic engineering have enabled the production of chemicals via bio-conversion using microbes. However, downstream separation accounts for 60–80% of the total production cost in many cases. Previous work on microbial production of extracellular chemicals has been mainly restricted to microbiology, biochemistry, metabolomics, or techno-economic analysis for specific product examples such as succinic acid, xanthan gum, lycopene, etc. In these studies, microbial production and separation technologies were selected apriori without considering any competing alternatives. However, technology selection in downstream separation and purification processes can have a major impact on the overall costs, product recovery, and purity. To this end, we apply a superstructure optimization based framework that enables the identification of critical technologies and their associated parameters in the synthesis and analysis of separation processes for extracellular chemicals generated from microbial conversions. We divide extracellular chemicals into three categories based on their physical properties, such as water solubility, physical state, relative density, volatility, etc. We analyze three major extracellular product categories (insoluble light, insoluble heavy and soluble) in detail and provide suggestions for additional product categories through extension of our analysis framework. The proposed analysis and results provide significant insights for technology selection and enable streamlined decision making when faced with any microbial product that is released extracellularly. The parameter variability analysis for the product as well as the associated technologies and comparison with novel alternatives is a key feature which forms the basis for designing better bioseparation strategies that have potential for commercial scalability and can compete with traditional chemical production methods.
Biliptysis
Authors: Elbahr Osama
Published: October 2019

Background

Biliptysis means coughing of bile which is a presenting symptom of a rare condition called bronchobiliary fistula (BBF). BBF is a connection between the biliary tract and bronchial tree. BBF mostly occurs secondary to malignancy, liver abscess, and trauma. Surgical approach in BBF management was the main management strategy, then endoscopic approach.

Case presentation

We managed our first encountered case of biliptysis endoscopically by endoscopic retrograde cholangiopancreatography (ERCP).

Conclusion

ERCP management seems to be effective in management of biliptysis.
Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial
Authors: Sharma Priyanka , Barlow William E. , Godwin Andrew K. , Parkes Eileen E. , Knight Laura A. , Walker Steven M. , Kennedy Richard D. , Harkin Denis P. , Logan Gemma E. , Steele Christopher J. , Lambe Shauna M. , Badve Sunil , Gökmen-Polar Yesim , Pathak Harsh B. , Isakova Kamilla , Linden Hannah M. , Porter Peggy , Pusztai Lajos , Thompson Alastair M. , Tripathy Debu , Hortobagyi Gabriel N. , Hayes Daniel F.
Published: October 2019

PURPOSE

To independently validate two biomarkers, a 44-gene DNA damage immune response (DDIR) signature and stromal tumor-infiltrating lymphocytes (sTILs), as prognostic markers in patients with triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin (A) and cyclophosphamide (C) in SWOG 9313.

METHODS

Four hundred twenty-five centrally determined patient cases with TNBC from S9313 were identified. DDIR signature was performed on RNA isolated from formalin-fixed paraffin-embedded tumor tissue, and samples were classified as DDIR negative or positive using predefined cutoffs. Evaluation of sTILs was performed as described previously. Markers were tested for prognostic value for disease-free survival (DFS) and overall survival (OS) using Cox regression models adjusted for treatment assignment, nodal status, and tumor size.

RESULTS

Among 425 patients with TNBC, 33% were node positive. DDIR was tested successfully in 90% of patients (381 of 425), 62% of which were DDIR signature positive. DDIR signature positivity was associated with improved DFS (hazard ratio [HR], 0.67; 95% CI, 0.48 to 0.92; P = .015) and OS (HR, 0.61; 95% CI, 0.43 to 0.89; P = .010). sTILs density assessment was available in 99% of patients and was associated with improved DFS (HR, 0.70; 95% CI, 0.51 to 0.96; P = .026 for sTILs density ≥ 20% v < 20%) and OS (HR, 0.59; 95% CI, 0.41 to 0.85; P = .004 for sTILs density ≥ 20% v < 20%). DDIR signature score and sTILs density were moderately correlated ( r = 0.60), which precluded statistical significance for DFS in a joint model. Three-year DFS and OS in a subgroup of patients with DDIR positivity and T1c/T2N0 disease were 88% and 94%, respectively.

CONCLUSION

The prognostic role of sTILs and DDIR in early-stage TNBC was confirmed. DDIR signature conferred improved prognosis in two thirds of patients with TNBC treated with adjuvant AC. DDIR signature has the potential to stratify outcome and to identify patients with less projected benefit after AC chemotherapy.
Teamwork as a Self-Disciplining Device
Authors: Fahn Matthias , Hakenes Hendrik
Published: October 2019

We show that team formation can serve as an implicit commitment device to overcome problems of self-control. If individuals have present-biased preferences, effort that is costly today but rewarded at some later point in time is too low from the perspective of an individual’s long-run self. If agents interact repeatedly and can monitor each other, a relational contract involving teamwork can help to improve performance. The mutual promise to work harder is credible because the team breaks up after an agent has not kept this promise, which leads to individual underproduction in the future, reducing future utility. (JEL D11, D71, D86, M54)
Trust the Police? Self-Selection of Motivated Agents into the German Police Force
Authors: Friebel Guido , Kosfeld Michael , Thielmann Gerd
Published: October 2019

We conduct experimental games with police applicants in Germany to investigate whether intrinsically motivated agents self-select into this type of public service. Our focus is on trustworthiness and the willingness to enforce norms of cooperation as key dimensions of intrinsic motivation in the police context. We find that police applicants are more trustworthy than non-applicants, i.e., they return higher shares as second-movers in a trust game. Furthermore, they invest more in rewards and punishment when they can enforce cooperation as a third party. Our results provide clear evidence for self-selection of motivated agents into the German police force, documenting an important mechanism that influences the match between jobs and agents in public service. (JEL C91, D73, J41, J45)
Peripheral nerve magnetic resonance imaging
Authors: Chen Yongsheng , Haacke E. Mark , Li Jun
Published: October 2019

Magnetic resonance imaging (MRI) has been used extensively in revealing pathological changes in the central nervous system. However, to date, MRI is very much underutilized in evaluating the peripheral nervous system (PNS). This underutilization is generally due to two perceived weaknesses in MRI: first, the need for very high resolution to image the small structures within the peripheral nerves to visualize morphological changes; second, the lack of normative data in MRI of the PNS and this makes reliable interpretation of the data difficult. This article reviews current state-of-the-art capabilities in in vivo MRI of human peripheral nerves. It aims to identify areas where progress has been made and those that still require further improvement. In particular, with many new therapies on the horizon, this review addresses how MRI can be used to provide non-invasive and objective biomarkers in the evaluation of peripheral neuropathies. Although a number of techniques are available in diagnosing and tracking pathologies in the PNS, those techniques typically target the distal peripheral nerves, and distal nerves may be completely degenerated during the patient’s first clinic visit. These techniques may also not be able to access the proximal nerves deeply embedded in the tissue. Peripheral nerve MRI would be an alternative to circumvent these problems. In order to address the pressing clinical needs, this review closes with a clinical protocol at 3T that will allow high-resolution, high-contrast, quantitative MRI of the proximal peripheral nerves.
What factors indicate prognosis for adults with depression in primary care? A protocol for meta-analyses of individual patient data using the Dep-GP database
Authors: Buckman Joshua E.J. , Saunders Rob , Cohen Zachary D. , Clarke Katherine , Ambler Gareth , DeRubeis Robert J. , Gilbody Simon , Hollon Steven D. , Kendrick Tony , Watkins Edward , White Ian R. , Lewis Glyn , Pilling Stephen
Published: October 2019

Background: Pre-treatment severity is a key indicator of prognosis for those with depression. Knowledge is limited on how best to encompass severity of disorders. A number of non-severity related factors such as social support and life events are also indicators of prognosis. It is not clear whether this holds true after adjusting for pre-treatment severity as a) a depressive symptom scale score, and b) a broader construct encompassing symptom severity and related indicators: “disorder severity”. In order to investigate this, data from the individual participants of clinical trials which have measured a breadth of “disorder severity” related factors are needed.

Aims: 1) To assess the association between outcomes for adults seeking treatment for depression and the severity of depression pre-treatment, considered both as i) depressive symptom severity only and ii) “disorder severity” which includes depressive symptom severity and comorbid anxiety, chronicity, history of depression, history of previous treatment, functional impairment and health-related quality of life.

2) To determine whether i) social support, ii) life events, iii) alcohol misuse, and iv) demographic factors (sex, age, ethnicity, marital status, employment status, level of educational attainment, and financial wellbeing) are prognostic indicators of outcomes, independent of baseline “disorder severity” and the type of treatment received.

Methods: Databases were searched for randomised clinical trials (RCTs) that recruited adults seeking treatment for depression from their general practitioners and used the same diagnostic and screening instrument to measure severity at baseline – the Revised Clinical Interview Schedule; outcome measures could differ between studies. Chief investigators of all studies meeting inclusion criteria were contacted and individual patient data (IPD) were requested.

Conclusions: In total 15 RCTs met inclusion criteria. The Dep-GP database will include the 6271 participants from the 13 studies that provided IPD. This protocol outlines how these data will be analysed.

Registration: PROSPERO CRD42019129512 (01/04/2019)
UKMenCar4: A cross-sectional survey of asymptomatic meningococcal carriage amongst UK adolescents at a period of low invasive meningococcal disease incidence
Authors: Bratcher Holly B. , Rodrigues Charlene M. C. , Finn Adam , Wootton Mandy , Cameron J. Claire , Smith Andrew , Heath Paul , Ladhani Shamez , Snape Matthew D. , Pollard Andrew J. , Cunningham Richard , Borrow Raymond , Trotter Caroline , Gray Stephen J. , Maiden Martin C. J. , MacLennan Jenny M.
Published: October 2019

Carriage of Neisseria meningitidis, the meningococcus, is a prerequisite for invasive meningococcal disease (IMD), a potentially devastating infection that disproportionately afflicts infants and children. Humans are the sole known reservoir for the meningococcus, and it is carried asymptomatically in the nasopharynx of ~10% of the population. Rates of carriage are dependent on age of the host and social and behavioural factors. In the UK, meningococcal carriage has been studied through large, multi-centre carriage surveys of adolescents in 1999, 2000, and 2001, demonstrating carriage can be affected by immunisation with the capsular group C meningococcal conjugate vaccine, inducing population immunity against carriage. Fifteen years after these surveys were carried out, invasive meningococcal disease incidence had declined from a peak in 1999.  The UKMenCar4 study was conducted in 2014/15 to investigate rates of carriage amongst the adolescent population during a period of low disease incidence. The protocols and methodology used to perform UKMenCar4, a large carriage survey, are described here.