bluuebunny/crossref_metadata_2025 huggingface dataset:
The 68Ga/177Lu-theragnostic concept in PSMA-targeting of metastatic castration–resistant prostate cancer: impact of post-therapeutic whole-body scintigraphy in the follow-up
Authors: Maffey-Steffan Johanna , Scarpa Lorenza , Svirydenka Anna , Nilica Bernhard , Mair Christian , Buxbaum Sabine , Bektic Jasmin , von Guggenberg Elisabeth , Uprimny Christian , Horninger Wolfgang , Virgolini Irene
Published: November 2019

Introduction

A new therapeutic option for metastatic castration–resistant prostate cancer (mCRPC) of heavily pre-treated patients lies in 177Lu-PSMA-617 radioligand therapy.

Methods

On the basis of PSMA-targeted 68Ga-PSMA-11 PET/CT, 32 consecutive mCRPC patients were selected for 177Lu-PSMA-617 therapy (6 GBq/cycle, 2 to 6 cycles, 6–10 weeks apart) and followed until death. Post-therapy whole-body (WB) dosimetry and 68Ga-PSMA-11 PET/CT data were compared and related to progression free and overall survival.

Results

177Lu-PSMA-617 dosimetry after the first cycle indicated high tumor doses for skeletal (4.01 ± 2.64; range 1.10–13.00 Gy/GBq), lymph node (3.12 ± 2.07; range 0.70–8.70 Gy/GBq), and liver (2.97 ± 1.38; range 0.76–5.00 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 24 GBq. Any PSA decrease after the first cycle was found in 23/32 (72%), after the second cycle in 22/32 (69%), after the third cycle in 16/28 (57%), and after the fourth cycle in 8/18 (44%) patients. Post-therapy 24 h WB scintigraphy showed decreased tumor-to-background ratios in 24/32 (75%) after the first therapy cycle, after the second cycle in 17/29 (59%), and after the third cycle in 13/21 (62%) patients. The median PFS was 7 months and the median OS 12 months. In the group of PSA responders (n = 22) the median OS was 17 months versus 11 months in the group of non-responders (n = 10), p < 0.05. Decreasing SUVmax values were found for parotid (15.93 ± 6.23 versus 12.33 ± 4.07) and submandibular glands (17.65 ± 7.34 versus 13.12 ± 4.62) following treatment, along with transient (n = 6) or permanent (n = 2) xerostomia in 8/32 (25%) patients. In 3/32 patients, nephrotoxicity changed from Grade 2 to 3, whereas neither Grade 4 nephrotoxicity nor hematotoxicity was found. In most patients a good agreement was observed for the visual interpretation of the tracer accumulation between 24 h WB and PET/CT scans. However, no significance could be calculated for baseline-absorbed tumor doses and SUVmax values of tumor lesions. 5/32 (16%) patients showed a mixed response pattern, which resulted in disease progression over time.

Conclusion

Serial PSA measurements and post-therapy 24 h WB scintigraphy seems to allow a sufficiently accurate follow-up of 177Lu-PSMA-617-treated mCRPC patients whereas 68Ga-PSMA-11 PET/CT should be performed for patient selection and final response assessment.
Historical reviews of the assessment of human cardiovascular function: interrogation and understanding of the control of skin blood flow
Authors: Low David. A. , Jones Helen , Cable N. Tim , Alexander Lacy M. , Kenney W. Larry
Published: November 2019

Several techniques exist for the determination of skin blood flow that have historically been used in the investigation of thermoregulatory control of skin blood flow, and more recently, in clinical assessments or as an index of global vascular function. Skin blood flow measurement techniques differ in their methodology and their strengths and limitations. To examine the historical development of techniques for assessing skin blood flow by describing the origin, basic principles, and important aspects of each procedure and to provide recommendations for best practise. Venous occlusion plethysmography was one of the earliest techniques to intermittently index a limb’s skin blood flow under conditions in which local muscle blood flow does not change. The introduction of laser Doppler flowmetry provided a method that continuously records an index of skin blood flow (red cell flux) (albeit from a relatively small skin area) that requires normalisation due to high site-to-site variability. The subsequent development of laser Doppler and laser speckle imaging techniques allows the mapping of skin blood flow from larger surface areas and the visualisation of capillary filling from the dermal plexus in two dimensions. The use of iontophoresis or intradermal microdialysis in conjunction with laser Doppler methods allows for the local delivery of pharmacological agents to interrogate the local and neural control of skin blood flow. The recent development of optical coherence tomography promises further advances in assessment of the skin circulation via three-dimensional imaging of the skin microvasculature for quantification of vessel diameter and vessel recruitment.
Sex-specific regulation of neuronal functions in Caenorhabditis elegans: the sex-determining protein TRA-1 represses goa-1/Gα(i/o)
Authors: Kutnyánszky Vera , Hargitai Balázs , Hotzi Bernadette , Kosztelnik Mónika , Ortutay Csaba , Kovács Tibor , Győry Eszter , Bördén Kincső , Princz Andrea , Tavernarakis Nektarios , Vellai Tibor
Published: November 2019

Females and males differ substantially in various neuronal functions in divergent, sexually dimorphic animal species, including humans. Despite its developmental, physiological and medical significance, understanding the molecular mechanisms by which sex-specific differences in the anatomy and operation of the nervous system are established remains a fundamental problem in biology. Here, we show that inCaenorhabditis elegans(nematodes), the global sex-determining factor TRA-1 regulates food leaving (mate searching), male mating and adaptation to odorants in a sex-specific manner by repressing the expression ofgoa-1gene, which encodes the Gα(i/o)subunit of heterotrimeric G (guanine–nucleotide binding) proteins triggering physiological responses elicited by diverse neurotransmitters and sensory stimuli. Mutations intra-1andgoa-1decouple behavioural patterns from the number of X chromosomes. TRA-1 binds to a conserved binding site located in thegoa-1coding region, and downregulatesgoa-1expression in hermaphrodites, particularly during embryogenesis when neuronal development largely occurs. These data suggest that the sex-determination machinery is an important modulator of heterotrimeric G protein-mediated signalling and thereby various neuronal functions in this organism and perhaps in other animal phyla.
Size-class structure of the forests of Finland during 1921–2013: a recovery from centuries of exploitation, guided by forest policies
Authors: Henttonen Helena M. , Nöjd Pekka , Suvanto Susanne , Heikkinen Juha , Mäkinen Harri
Published: November 2019

Frequency distributions of tree diameters are a powerful tool for analyzing changes of tree populations in large areas. We analyzed the densities and mean volume estimates of trees in different size classes for the Finnish forests over the time-span of the National Forest Inventories (1921–2013). The results display a general increase in trees in all size classes, species group and geographical area, mainly after the 1970s. The densities of medium- and large-sized conifers showed large increases in the southern boreal subzone, spruces even more than pines. Small- to medium-sized pines have increased in the middle and northern boreal subzones. The shifts in growing stock are related to changing land use, resulting from the development of the society. The low quantities of both growing stock and large trees during the 1920s reflect a poor initial state of forests. Several land use forms of the former agriculture-based society were detrimental to forests, including slash and burn agriculture, cattle grazing and tar production. The pressure from alternative land use forms was stronger in southern Finland, where the population density (people per km2) is much higher. Between 1971 and 2013, the changes in size-class structure can be attributed mainly to intensified silviculture boosted by actions of the Finnish governments, including both legislation and financial support for management activities. Not only the development of growing stock has exceeded expectations, but the increase has also concentrated in the economically valuable trees in the large size classes.
Correction to: Web-Based Intervention and Email‑Counseling for Problem Gamblers: Results of a Randomized Controlled Trial
Authors: Jonas Benjamin , Leuschner Fabian , Eiling Anna , Schoelen Christine , Soellner Renate , Tossmann Peter
Published: November 2019

The article “Web-Based Intervention and Email-Counseling for Problem Gamblers: Results of a Randomized Controlled Trial” was written by Benjamin Jonas, Fabian Leuschner, Anna Eiling, Christine Schoelen, Renate Soellner and Peter Tossmann.
Enzymatic Degradation and Pilot-Scale Composting of Cellulose-Based Films with Different Chemical Structures
Authors: Leppänen Ilona , Vikman Minna , Harlin Ali , Orelma Hannes
Published: November 2019

In this study, we investigated the enzymatical degradability and pilot-scale composting of 14 cellulose-based materials. The materials analyzed here were cellulose regenerated from ionic liquid (EMIM[OAc]), carboxymethyl cellulose (CMC) crosslinked by aluminum salt (Al-salt), methyl cellulose, cellulose acetate, butylated hemicellulose: DS: 1, DS: 0.4, and DS: 0.2, cellophane, wet strength paper, nanocellulose, paper partially dissolved by IL, cellulose carbamate, cellulose palmitate, and cellulose octanoate. The aim of the study was to show how chemical substituting and the substituent itself influence the biodegradability of cellulose materials. The enzymatic degradation and pilot-scale composting of these films shows the correlation between the hydrolysis rate and degree of substitution. The enzymatic hydrolysis of cellulose-based films decreased exponentially as the degree of substitution increased. Modifying cellulose to the extent that it gains the strength needed to obtain good mechanical properties, while retaining its natural biodegradability is an important factor when preparing alternatives for plastic films.

Graphic Abstract
Panlongcheng, Zhengzhou and the Movement of Metal in Early Bronze Age China
Authors: Liu Ruiliang , Pollard A. Mark , Rawson Jessica , Tang Xiaojia , Bray Peter , Zhang Changping
Published: November 2019

The role of Panlongcheng—a walled settlement on the Yangtze River with obvious links to the Erligang capital at Zhengzhou, ~ 500 km to the north—in early Bronze Age China has been the subject of much debate. Panlongcheng is a typical Erligang site (~ 1500–1300 BC), with evidence for people of elite status, unlike any other site apart from Zhengzhou itself. The tombs and bronzes at Panlongcheng, as well as other materials, closely resemble those at Zhengzhou. Why was Panlongcheng established along the Yangtze River, and what were the Erligang elites doing there? Considering the rich copper deposits in this area, it is widely assumed that the major function of Panlongcheng was to ship metal to Zhengzhou, and in return to receive bronze vessels from Zhengzhou. The purpose of this paper is to revisit this discussion through a re-evaluation of the scientific data on the bronzes from each site. A series of differences and similarities in the chemical and isotopic compositions of the metal objects at Panlongcheng and Zhengzhou are identified, suggesting that the relationship was more complex than was previously thought. In this light, despite a close social and presumably political affiliation with Zhengzhou, Panlongcheng appears likely to have had its own metal-casting capability, rather than having to rely completely on finished objects imported from Zhengzhou. This discovery encourages scholars to re-consider the metal supply network and the underlying political landscape in early dynastic China, shifting from a linear model to a complex but probably more realistic one.
Model-Based Geostatistics from a Bayesian Perspective: Investigating Area-to-Point Kriging with Small Data Sets
Authors: Steinbuch Luc , Orton Thomas G. , Brus Dick J.
Published: November 2019

Area-to-point kriging (ATPK) is a geostatistical method for creating high-resolution raster maps using data of the variable of interest with a much lower resolution. The data set of areal means is often considerably smaller ($$<\,50 $$<50 observations) than data sets conventionally dealt with in geostatistical analyses. In contemporary ATPK methods, uncertainty in the variogram parameters is not accounted for in the prediction; this issue can be overcome by applying ATPK in a Bayesian framework. Commonly in Bayesian statistics, posterior distributions of model parameters and posterior predictive distributions are approximated by Markov chain Monte Carlo sampling from the posterior, which can be computationally expensive. Therefore, a partly analytical solution is implemented in this paper, in order to (i) explore the impact of the prior distribution on predictions and prediction variances, (ii) investigate whether certain aspects of uncertainty can be disregarded, simplifying the necessary computations, and (iii) test the impact of various model misspecifications. Several approaches using simulated data, aggregated real-world point data, and a case study on aggregated crop yields in Burkina Faso are compared. The prior distribution is found to have minimal impact on the disaggregated predictions. In most cases with known short-range behaviour, an approach that disregards uncertainty in the variogram distance parameter gives a reasonable assessment of prediction uncertainty. However, some severe effects of model misspecification in terms of overly conservative or optimistic prediction uncertainties are found, highlighting the importance of model choice or integration into ATPK.
The True Story on Deficiencies After Sleeve Gastrectomy: Results of a Double-Blind RCT
Authors: Heusschen Laura , Schijns Wendy , Ploeger Nadine , Deden Laura N. , Hazebroek Eric J. , Berends Frits J. , Aarts Edo O.
Published: November 2019

Background

Since a few years, the laparoscopic sleeve gastrectomy (SG) has become the most performed bariatric operation worldwide. However, as with all bariatric procedures, SG also leads to vitamin and mineral deficiencies post-operatively and standard multivitamin supplements are probably not sufficient.

Objective

The present study evaluates the effectiveness of a specialized multivitamin supplement for SG patients (WLS Optimum 1.0, FitForMe, Rotterdam, the Netherlands), compared to a standard multivitamin supplement (sMVS).

Design

A double-blind randomized controlled trial was performed. For 12 months, patients in the intervention group received WLS Optimum, containing elevated doses of multiple vitamins and minerals. Patients in the control group were provided with sMVS, containing 100% of the recommended dietary allowance.

Results

In total, 139 patients were available for analysis (WLS Optimum, n = 69; sMVS, n = 70). Intention-to-treat analyses revealed more folic acid deficiencies and higher serum vitamin B1 levels in the WLS Optimum group. Per protocol analyses showed that in patients using WLS Optimum, serum folic acid and vitamin B1 levels were higher, serum PTH levels were lower, and only one patient (2.6%) was anemic compared to 11 patients (17.5%) using a sMVS (p < 0.05 for all). No differences were found in prevalence of deficiencies for iron, vitamin B12, vitamin D, and other vitamins and minerals.

Conclusions

This optimized multivitamin supplement only affected serum levels of folic acid, PTH and vitamin B1, and anemia rates compared to a sMVS. There is a clear need to further optimize multivitamin supplementation for SG patients. Besides, non-compliance with multivitamin supplements remains an important issue that should be dealt with.

Clinical Trial Registry

The study protocol was registered at the clinical trials registry of the National Institutes of Health (ClinicalTrials.gov; identifier NCT01609387).
Detrusor Underactivity and Underactive Bladder in Women: What Is New?
Authors:   EAU Young Academic Urologists (YAU) Functional Urology Working Group, Osman N. I. , Pang K. H. , Martens F. , Atunes-Lopes T. , Geavlete B. , Husch T. , Tutolo M. , Rahnama’i M. S. , Marcelissen T.
Published: November 2019

Purpose of Review

Detrusor underactivity (DU) and its symptom-based correlation, the underactive bladder (UAB), are common problems encountered in urological practice. Whilst DU has been defined for many years, only recently has UAB received a formal definition and there is now accumulating literature based on this condition. In this article, we reviewed the recent literature on the aetiology, pathogenesis, diagnosis and management of DU/UAB in women.

Recent Findings

Detrusor underactivity is diagnosed on urodynamic studies but there still remains a lack of widely recognised and accepted diagnostic criteria. Commencing treatment based on the diagnosis of UAB, with or without a PVR measurement, is perhaps feasible due to the lower occurrence of BOO in women and specific clinical features that may distinguish this group. Prospective studies attempting to correlate UAB with the underlying DU are needed before this approach could be considered.

Detrusor underactivity/UAB in women requires a separate consideration from men due to the anatomical and functional differences in the lower urinary tracts between both genders and consequent differences in pathologies affecting them. The aetiology of DU remains largely unknown, but is probably multifactorial, including myogenic, neurogenic and vasculogenic factors. There remains a lack of any simple effective drug treatments, whilst apart from sacral neuromodulation for the specific subgroup with non-obstructive urinary retention, no safe and effective surgical treatment is currently available. Often, permanent or intermittent bladder drainage with a catheter is the final solution.
Thiazolidinediones: the Forgotten Diabetes Medications
Authors: Lebovitz Harold E.
Published: November 2019

Purpose of Review

Thiazolidinediones (TZDs) are the only pharmacologic agents that specifically treat insulin resistance. The beneficial effects of TZDs on the cardiovascular risk factors associated with insulin resistance have been well documented. TZD use has been limited because of concern about safety issues and side effects.

Recent Findings

Recent studies indicate that cardiovascular toxicity with rosiglitazone and increase in bladder cancer with pioglitazone are no longer significant issues. There are new data which show that pioglitazone treatment reduces myocardial infarctions and ischemic strokes. New data concerning TZD-mediated edema, congestive heart failure, and bone fractures improves the clinician’s ability to select patients that will have minimal significant side effects.

Thiazolidinediones are now generic and less costly than pharmaceutical company–promoted therapies. Better understanding of the side effects coupled with clear benefits on the components of the insulin resistance syndrome should promote TZD use in treating patients with type 2 diabetes.
Maternal mortality due to cardiovascular disease in the Netherlands: a 21-year experience
Authors:   Dutch Maternal Mortality and Morbidity Committee, Lameijer H. , Schutte J. M. , Schuitemaker N. W. E. , van Roosmalen J. J. M. , Pieper P. G.
Published: November 2019

Objective

Cardiovascular disorders are the leading cause of indirect maternal mortality in Europe. The aim of this study is to present an extensive overview concerning the specific cardiovascular causes of maternal death and to identify avoidable contributing care factors related to these deaths.

Methods

We assessed all cases of maternal death due to cardiovascular disorders collected by a systematic national confidential enquiry of maternal deaths published by the Dutch Maternal Mortality and Morbidity Committee on behalf of the Netherlands Society of Obstetrics and Gynaecology over a 21-year period (1993–2013) in the Netherlands.

Results

There were 96 maternal cardiovascular deaths (maternal mortality rate due to cardiovascular diseases 2.4/100,000 liveborn children). Causes were aortic dissection (n = 20, 21%), ischaemic heart disease (n = 17, 18%), cardiomyopathies (including peripartum cardiomyopathy and myocarditis, n = 20, 21%) and (unexplained) sudden death (n = 27, 28%). Fifty-five percent of the deaths occurred postpartum (n = 55, 55%). Care factors that may have contributed to the adverse outcome were identified in 27 cases (28%). These factors were patient-related in 40% (pregnancy against medical advice, underestimation of symptoms) and healthcare-provider-related in 60% (symptoms not recognised, delay in diagnosis, delay in referral).

Conclusion

The maternal cardiovascular mortality ratio is low in the Netherlands and the main causes of maternal cardiovascular mortality are in line with other European reports. In a minority of cases, care factors that were possibly preventable were identified. Women with cardiovascular disease should be properly counselled about the risks of pregnancy and the symptoms of complications. Education of care providers regarding the incidence, presentation and diagnosis of cardiovascular disease during pregnancy is recommended.
Biological age estimation using an eHealth system based on wearable sensors
Authors: Pierleoni Paola , Belli Alberto , Concetti Roberto , Palma Lorenzo , Pinti Federica , Raggiunto Sara , Sabbatini Luisiana , Valenti Simone , Monteriù Andrea
Published: November 2019

The rapid worldwide aging makes necessary the development of advanced technologies for the objective identification of diseases and disabilities onset. Accordingly, we need to regard the biological age as an alternative and more reliable indicator of the physiological decline of individuals, respect to the simple chronological age. In this paper, we present an eHealth system for estimate the biological age of elderly people starting from the assessment of the frailty phenotype. The frailty phenotype evaluation is made possible using a standard protocol for data acquisition and a cloud application for processing and storing data. The proposed eHealth system is also equipped with wireless, small and non-invasive wearable sensors for an objective evaluation of the mobility of a subject. The eHealth system is tested on a reference population in order to have an amount of data necessary for defining a model to estimate the biological age. The use of the presented system on a reference population, and the availability of data regarding their mobility, allow the validation of the proposed model for the computation of the biological age via simple and objective frailty phenotype assessment.
Seismic reflection pattern and attribute analysis as a tool for defining reservoir architecture in ‘SABALO’ field, deepwater Niger Delta
Authors: Fashagba Imoleayo , Enikanselu Pius , Lanisa Ademola , Matthew Olabode
Published: November 2019

An accurate definition of environment of sediment deposition is a sine qua non for characterizing and providing measures for enhancing hydrocarbon reservoirs. Consequently, this study is aimed at determining the sub-environment of deposition and architecture of two reservoirs: S1000 and S2000 reservoirs, in ‘SABALO’ field, deep offshore Niger Delta. In addition, the study is imperative in order to assess reservoir properties such as: geometry, connectivity and continuity, which are important for exploration and reservoir management. In this study, we integrated well logs from six (6) wells and 3D-seismic data (near and far angle stack) for seismic stratigraphic studies. Four major seismic sequences with their corresponding facies units were recognized by analysis of reflection terminations, seismic parameters and external geometry. The reservoirs of interest are within the seismic sequence one containing facies units: SF1A and SF1B. Both reservoirs were delineated to be structurally and stratigraphically controlled. This implies a combinational trapping system at the reservoir level. Also, hydrocarbons in the reservoir were confirmed to be down to reservoir base. Integrated study of the seismic and well logs shows that the two identified reservoirs, S1000 and S2000, were defined to be weakly confined channel complex with an area of 50 km2 and 78 km2, respectively. Their connectivity was defined to be loosely amalgamated and highly amalgamated, respectively. The results of this paper are essential to develop the reservoirs by utilizing the information of their geometry, connectivity and continuity.
What Do Students Perceive as Ethical Problems? A Comparative Study of Dutch and Indonesian Medical Students in Clinical Training
Authors: Muhaimin Amalia , Willems Derk Ludolf , Utarini Adi , Hoogsteyns Maartje
Published: November 2019

Previous studies show that medical students in clinical training face ethical problems that are not often discussed in the literature. In order to make teaching timely and relevant for them, it is important to understand what medical students perceive as ethical problems, as various factors may influence their perception, including cultural differences and working environment. The purpose of this qualitative study was to explore students’ perceptions of what an ethical problem is, during their clinical training in the hospital, and compare the results from two different countries. We observed a total of eighteen ethics group discussions and interviewed fifteen medical students at two medical schools, in Indonesia and the Netherlands. Data were interpreted and analyzed using content analysis. We found that students in both settings encounter problems which are closer to their daily work and responsibilities as medical students and perceive these problems as ethical problems. Indonesian students perceived substandard care and inequity in healthcare as ethical problems, while Dutch students perceived that cases which are not matters of life and death are less worthy to discuss. Our study suggests that there might be a gap between ethical problems that are discussed in class with teachers, and problems that students actually encounter in practice. Teachers should be aware of the everyday situations in clinical training which may be perceived by students as ethically problematic and should acknowledge and discuss these ethical problems with students as part of the learning processes in ethics education.
Assessing parental awareness and attitudes toward leaving children unattended inside locked cars and the risk of vehicular heat strokes
Authors: Alowirdi Fatimah S. , Al-harbi Shaikhah A. , Abid Omer , Aldibasi Omar S. , Jamil Syed F.
Published: November 2019

Background:

Vehicular heat stroke is considered as one of the preventable causes of non-crash, vehicle- related deaths among children. The prevalence of parents and caregivers leaving children unattended in enclosed vehicles is non-negligible.

Objective:

This paper aims to assess parents' knowledge and beliefs about vehicular heat strokes among children in addition to the prevalence and associated factors of leaving children inside locked cars.

Methods:

A cross-sectional study was carried out at King Abdullah Specialist Children's Hospital in Riyadh. Two hundred nine parents completed a self-administered questionnaire addressing vehicular heat strokes.

Results:

Among the participants, 24.88% have left at least one of their children unattended inside locked cars during a sunny day; 78.85% of parents have heard about accidental deaths secondary to leaving children in locked vehicles. When assessing parental knowledge of increased sensitivity to heat in in- fants/children, 81.34% of them knew the correct information. Older age (P = .0150), less paternal education (P = .0157), and increased number of children (P = .0020) were associated with increased incidences of leaving children unattended in enclosed cars.

Conclusion:

Considering the high temperatures in the Gulf region, the prevalence of vehicular heat stroke secondary to locking children inside vehicles is nontrivial. Awareness programs for parents and caregivers are strongly encouraged.
Ontario Pension Policy Making and the Politics of CPP Reform, 1963–2016
Authors: Christensen Benjamin
Published: November 2019

After years of pension policy drift in a broader context of global austerity, the Canada Pension Plan (CPP) was enhanced for the first time in 2016 to expand benefits for Canadian workers. This article examines Ontario's central role in these reforms. The deteriorating condition of workplace plans, coupled with rising retirement income insecurity across the province's labour force, generated new sources of negative feedback at the provincial level, fuelling Ontario's campaign for CPP reform beginning in the late 2000s. The political limits of policy drift and layering at the provincial level is considered in relationship to policy making at the national level. As shown, a new period of pension politics emerged in Canada after 2009, in which the historical legacy of CPP's joint governance structure led to a dynamic of “collusive benchmarking,” shaped in large part by political efforts of the Ontario government, leading to CPP enhancement.
Effects of nasal lavage with and without mupirocin after endoscopic endonasal skull base surgery: a randomised, controlled study
Authors: Ng B H K , Tang I P , Narayanan P , Raman R , Carrau R L
Published: November 2019

Background

Nasal lavage with mupirocin has the potential to reduce sinonasal morbidity in endoscopic endonasal approaches for skull base surgery.

Objective

To evaluate the effects of nasal lavage with and without mupirocin after endoscopic endonasal skull base surgery.

Methods

A pilot randomised, controlled trial was conducted on 20 adult patients who had undergone endoscopic endonasal approaches for skull base lesions. These patients were randomly assigned to cohorts using nasal lavages with mupirocin or without mupirocin. Patients were assessed in the out-patient clinic, one week and one month after surgery, using the 22-item Sino-Nasal Outcome Test questionnaire and nasal endoscopy.

Results

Patients in the mupirocin nasal lavage group had lower nasal endoscopy scores post-operatively, and a statistically significant larger difference in nasal endoscopy scores at one month compared to one week. The mupirocin nasal lavage group also showed better Sino-Nasal Outcome Test scores at one month compared to the group without mupirocin.

Conclusion

Nasal lavage with mupirocin seems to yield better outcomes regarding patients’ symptoms and endoscopic findings.
Right-Wing Moderation, Left-Wing Inertia and Political Cartelisation in Post-Transition Chile
Authors: Madariaga Aldo , Rovira Kaltwasser Cristóbal
Published: November 2019

By examining the Manifesto Project data for post-transition Chile, we show growing convergence in the electoral competition strategies between the centre-left and centre-right coalitions. While the former is characterised by inertia, the latter is marked by gradual yet relentless programmatic moderation. To interpret these results, we rely not only on theories of salience and party adaptation, but also on the cartel party thesis. This contribution reinforces the findings of increasing literature on post-transition Chile that reveals growing collusion between the mainstream left-wing and right-wing coalitions, which have increasing difficulties channelling demands emanating from below and therefore providing adequate political representation.
Terms of empowerment: of conservation or communities?
Authors: Petriello Michael A. , Redmore Lauren , Sène-Harper Aby , Katju Dhananjaya
Published: November 2019

In this era of socially-oriented biodiversity conservation and resource management, practitioners and scholars all too often invoke unclear and imprecise claims of empowerment to describe changing relations between people and resources. Empowerment is an important indicator of conservation success and social transformation. Yet, when scholars and practitioners fail to adequately conceptualize empowerment, they run the risk of undermining the importance of local involvement and capacity building to achieve biodiversity conservation. Here we explore the many ways empowerment has been conceptualized in conservation. We root our commentary in the history of the use of empowerment in conservation from these diverse perspectives. We then present examples of different meanings, measurements and outcomes ascribed to empowerment. We conclude with suggestions for harnessing empowerment for the benefit of conservationists and communities alike. Because empowerment has the potential to improve resource management outcomes and local livelihoods, we recommend building an adaptive empowerment assessment framework to assist with its deployment where it is most needed. Although empowerment goals in conservation can guide practitioners and scholars to engage with communities in transparent, meaningful and lasting ways, conservation needs a critical approach that builds from an appreciation of the nuances underlying the purpose and power of empowerment for conservation.
Implementing health technology assessment in Kuwait: a qualitative study of perceived barriers and facilitators
Authors: Darawsheh Basshar , Germeni Evi
Published: November 2019

Objectives

This study sought to explore main barriers and facilitators to implementing health technology assessment (HTA) in Kuwait from the perspective of key stakeholders.

Methods

Semi-structured qualitative interviews were conducted with ten key stakeholders: seven healthcare providers working at various departments of the Kuwaiti Ministry of Health (MOH), and three academics with substantial experience in teaching HTA or related fields. Interviews were conducted face-to-face, audio-recorded, and transcribed verbatim. Data were analyzed using an inductive thematic approach.

Results

Participating stakeholders reported several factors that might act as a barrier to building HTA in Kuwait: minimal awareness of HTA, lack of institutional and human capacity, a fragmented healthcare system, poor communication between researchers and policy makers, the country's wealth, politics, as well as data quality, availability, and sharing. Institutionalizing HTA as a politically empowered body, enforcing its recommendation by law, and benefiting from neighboring countries' experiences were suggested as possible ways to move forward.

Conclusion

Studies exploring the unique challenges that high-income developing countries may face in implementing HTA are still scarce. The results of this study are consistent with evidence coming from other developing countries, while also suggesting that the abundance of financial resources in the country is a double-edged sword; it has the potential to facilitate the development of HTA capacity, but also hinders recognizing the need for it.
Heart failure biomarker levels correlate with invasive haemodynamics in pulmonary valve replacement
Authors: Zegelbone Phillip M. , Ringel Richard E. , Coulson John D. , Nies Melanie K. , Stabler Meagan E. , Brown Jeremiah R. , Everett Allen D.
Published: November 2019

Background:

Although widely used in cardiology, relation of heart failure biomarkers to cardiac haemodynamics in patients with CHD (and in particular with pulmonary insufficiency undergoing pulmonary valve replacement) remains unclear. We hypothesised that the cardiac function biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity 2, and galectin-3 would have significant associations to right ventricular haemodynamic derangements.

Methods:

Consecutive patients ( n = 16) undergoing cardiac catheterisation for transcatheter pulmonary valve replacement were studied. NT-proBNP, soluble suppressor of tumorigenicity 2, and galectin-3 levels were measured using a multiplex enzyme-linked immunosorbent assay from a pre-intervention blood sample obtained after sheath placement. Spearman correlation was used to identify significant correlations (p ≤ 0.05) of biomarkers with baseline cardiac haemodynamics. Cardiac MRI data (indexed right ventricular and left ventricular end-diastolic volumes and ejection fraction) prior to device placement were also compared to biomarker levels.

Results:

NT-proBNP and soluble suppressor of tumorigenicity 2 were significantly correlated (p < 0.01) with baseline mean right atrial pressure and right ventricular end-diastolic pressure. Only NT-proBNP was significantly correlated with age. Galectin-3 did not have significant associations in this cohort. Cardiac MRI measures of right ventricular function and volume were not correlated to biomarker levels or right heart haemodynamics.

Conclusions:

NT-proBNP and soluble suppressor of tumorigenicity 2, biomarkers of myocardial strain, significantly correlated to invasive pressure haemodynamics in transcatheter pulmonary valve replacement patients. Serial determination of soluble suppressor of tumorigenicity 2, as it was not associated with age, may be superior to serial measurement of NT-proBNP as an indicator for timing of pulmonary valve replacement.
The Road Ahead…
Authors: Goss Heather
Published: November 2019

We’re closing out our Centennial year by celebrating all that our community has accomplished together and getting inspired for what comes next.
Machine Fault
Authors: Pratt Sara
Published: November 2019

Applying machine learning to subtle acoustic signals from an earthquake machine has revealed big clues about fault behavior in the lab.
A New Method for Distinguishing Unactivated Particles in Cloud Condensation Nuclei Measurements: Implications for Aerosol Indirect Effect Evaluation
Authors: Wang Yuan , Niu Shengjie , Lv Jingjing , Lu Chunsong , Xu Xiaoqi , Wang Yuying , Ding Jie , Zhang Hongwei , Wang Tianshu , Kang Boshi
Published: November 2019

An ongoing challenge for cloud condensation nuclei (CCN) measurements is the inclusion of unactivated particles, which affects droplet activation parameterizations and aerosol indirect effects in models. For the first time, a reciprocal relationship between the critical diameter and critical supersaturation of activated droplets from the κ‐Köhler theory is derived to accurately count unactivated particles in CCN measurements. We conducted 4‐day continuous observations to simultaneously measure the number concentration of CCN (NCCN) and aerosol. The results show that as supersaturation (SS) decreases from 0.186% at 25 °C, the proportion of the unactivated particles in the CCN measurements increases, reaching 88% at SS of 0.07%. Owing to the NCCN overestimation caused by NCCN‐SS parameterizations with uncorrected NCCN, there is significant overestimation of aerosol indirect effects, especially under low SS conditions. After removing unactivated particles, NCCN‐SS parameterizations are adjusted accordingly, which can improve simulations of aerosol‐cloud‐radiation interactions in models.
Paleoenvironmental Changes at ODP Site 702 (South Atlantic): Anatomy of the Middle Eocene Climatic Optimum
Authors: Rivero‐Cuesta L. , Westerhold T. , Agnini C. , Dallanave E. , Wilkens R. H. , Alegret L.
Published: November 2019

The Middle Eocene Climatic Optimum (MECO) was an unusual global warming event that interrupted the long‐term Eocene cooling trend ca. 40 Ma. Here we present new high‐resolution bulk and benthic isotope records from South Atlantic ODP Site 702 to characterize the MECO at a high latitude setting. The MECO event, including early and peak warming as well as recovery to background levels, had an estimated ~300 Kyr duration (~40.51 to ~40.21 Ma). Cross‐plots (δ18O vs. δ13C) suggest that the mechanisms driving coupled changes in O and C isotope values across the MECO were weaker or absent before the event. The paleoecological response has been evaluated by quantitative analysis of calcareous nannofossils and benthic foraminifera assemblages. We document a shift in the biogeographical distribution of warm and temperate calcareous nannoplankton taxa, which migrated toward higher latitudes due to increased temperatures during the MECO. Conversely, changes in the organic matter flux to the seafloor appear to have controlled benthic foraminifera dynamics at Site 702. Benthic phytodetritus exploiting taxa increased in abundance coinciding with a positive δ13C excursion, ~150 Kyr before the start of the δ18O negative excursion that marks the start of MECO warming. Our data suggest that paleoecological disturbance in the deep sea predates MECO δ18O excursion and that it was driven by changes in the type and/or amount of organic matter reaching the seafloor rather than by increased temperature.
Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment
Authors: Caye Aurélie , Rouault-Pierre Kevin , Strullu Marion , Lainey Elodie , Abarrategi Ander , Fenneteau Odile , Arfeuille Chloé , Osman Jennifer , Cassinat Bruno , Pereira Sabrina , Anjos-Afonso Fernando , Currie Erin , Ariza-McNaughton Linda , Barlogis Vincent , Dalle Jean-Hugues , Baruchel André , Chomienne Christine , Cavé Hélène , Bonnet Dominique
Published: November 2019

Juvenile myelomonocytic leukemia (JMML) is a rare aggressive myelodysplastic/myeloproliferative neoplasm of early childhood, initiated by RAS-activating mutations. Genomic analyses have recently described JMML mutational landscape; however, the nature of JMML-propagating cells (JMML-PCs) and the clonal architecture of the disease remained until now elusive. Combining genomic (exome, RNA-seq), Colony forming assay and xenograft studies, we detect the presence of JMML-PCs that faithfully reproduce JMML features including the complex/nonlinear organization of dominant/minor clones, both at diagnosis and relapse. Further integrated analysis also reveals that although the mutations are acquired in hematopoietic stem cells, JMML-PCs are not always restricted to this compartment, highlighting the heterogeneity of the disease during the initiation steps. We show that the hematopoietic stem/progenitor cell phenotype is globally maintained in JMML despite overexpression of CD90/THY-1 in a subset of patients. This study shed new lights into the ontogeny of JMML, and the identity of JMML-PCs, and provides robust models to monitor the disease and test novel therapeutic approaches.
Protrudin modulates seizure activity through GABAA receptor regulation
Authors: Lu Xi , Yang Yong , Zhou Ruijiao , Li Yun , Yang Yi , Wang Xuefeng
Published: November 2019

Epilepsy is a serious neurological disease characterized by recurrent unprovoked seizures. The exact etiology of epilepsy is not fully understood. Protrudin is a neural membrane protein and is found to be mutated in hereditary spastic paraplegia that characterized by symptoms like seizures. Here, we reported that the expression of protrudin was downregulated in the temporal neocortex of epileptic patients and in the hippocampus and cortex of pentylenetetrazol and kainic acid-kindled epileptic mouse models. Behavioral and electroencephalogram analyses indicated that overexpression of protrudin in the mouse hippocampus increased the latency of the seizure and decreased the frequency and duration of seizure activity. Using whole-cell patch clamp, overexpression of protrudin in the mouse hippocampus resulted in a reduction in action potential frequency and an increase in gamma-aminobutyric acid (GABA)ergic inhibitory current amplitude. Moreover, western blot analysis showed that the membrane expression of the GABA A receptor β2/3 subunit was also upregulated after protrudin overexpression, and coimmunoprecipitation resulted in a protein–protein interaction between protrudin, GABAARβ2/3 and GABA receptor-associated protein in the hippocampus of epileptic mice. These findings suggest that protrudin probably inhibits the occurrence and development of epilepsy through the regulation of GABAA receptor-mediated synaptic transmission, and protrudin might be a promising target for the treatment of epilepsy.
The preponderance of nonsynonymous A-to-I RNA editing in coleoids is nonadaptive
Authors: Jiang Daohan , Zhang Jianzhi
Published: November 2019

A-to-I editing enzymatically converts the base adenosine (A) in RNA molecules to inosine (I), which is recognized as guanine (G) in translation. Exceptionally abundant A-to-I editing was recently discovered in the neural tissues of coleoids (octopuses, squids, and cuttlefishes), with a greater fraction of nonsynonymous sites than synonymous sites subject to high levels of editing. Although this phenomenon is thought to indicate widespread adaptive editing, its potential advantage is unknown. Here we propose an alternative, nonadaptive explanation. Specifically, increasing the cellular editing activity permits some otherwise harmful G-to-A nonsynonymous substitutions, because the As are edited to Is at sufficiently high levels. These high editing levels are constrained upon substitutions, resulting in the predominance of nonsynonymous editing at highly edited sites. Our evidence for this explanation suggests that the prevalent nonsynonymous editing in coleoids is generally nonadaptive, as in species with much lower editing activities.
Cytoplasmic glycoengineering enables biosynthesis of nanoscale glycoprotein assemblies
Authors: Tytgat Hanne L. P. , Lin Chia-wei , Levasseur Mikail D. , Tomek Markus B. , Rutschmann Christoph , Mock Jacqueline , Liebscher Nora , Terasaka Naohiro , Azuma Yusuke , Wetter Michael , Bachmann Martin F. , Hilvert Donald , Aebi Markus , Keys Timothy G.
Published: November 2019

Glycosylation of proteins profoundly impacts their physical and biological properties. Yet our ability to engineer novel glycoprotein structures remains limited. Established bacterial glycoengineering platforms require secretion of the acceptor protein to the periplasmic space and preassembly of the oligosaccharide substrate as a lipid-linked precursor, limiting access to protein and glycan substrates respectively. Here, we circumvent these bottlenecks by developing a facile glycoengineering platform that operates in the bacterial cytoplasm. The Glycoli platform leverages a recently discovered site-specific polypeptide glycosyltransferase together with variable glycosyltransferase modules to synthesize defined glycans, of bacterial or mammalian origin, directly onto recombinant proteins in the E. coli cytoplasm. We exploit the cytoplasmic localization of this glycoengineering platform to generate a variety of multivalent glycostructures, including self-assembling nanomaterials bearing hundreds of copies of the glycan epitope. This work establishes cytoplasmic glycoengineering as a powerful platform for producing glycoprotein structures with diverse future biomedical applications.
Engineering dendritic cell vaccines to improve cancer immunotherapy
Authors: Perez Caleb R. , De Palma Michele
Published: November 2019

At the interface between the innate and adaptive immune system, dendritic cells (DCs) play key roles in tumour immunity and hold a hitherto unrealized potential for cancer immunotherapy. Here we review the role of distinct DC subsets in the tumour microenvironment, with special emphasis on conventional type 1 DCs. Integrating new knowledge of DC biology and advancements in cell engineering, we provide a blueprint for the rational design of optimized DC vaccines for personalized cancer medicine.