bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracking pyrethroid toxicity in surface water samples: Exposure dynamics and toxicity identification tools for laboratory tests with Hyalella azteca (Amphipoda)
Authors: Deanovic Linda A. , Stillway Marie , Hammock Bruce G. , Fong Stephanie , Werner Inge
Published: September 2017

Pyrethroid insecticides are commonly used in pest control and are present at toxic concentrations in surface waters of agricultural and urban areas worldwide. Monitoring is challenging as a result of their high hydrophobicity and low toxicity thresholds, which often fall below the analytical methods detection limits (MDLs). Standard daphnid bioassays used in surface water monitoring are not sensitive enough to protect more susceptible invertebrate species such as the amphipod Hyalella azteca and chemical loss during toxicity testing is of concern. In the present study, we quantified toxicity loss during storage and testing, using both natural and synthetic water, and presented a tool to enhance toxic signal strength for improved sensitivity of H. azteca toxicity tests. The average half-life during storage in low-density polyethylene (LDPE) cubitainers (Fisher Scientific) at 4 °C of 5 pyrethroids (permethrin, bifenthrin, lambda-cyhalothrin, cyfluthrin, and esfenvalerate) and one organophosphate (chlorpyrifos; used as reference) was 1.4 d, and piperonyl butoxide (PBO) proved an effective tool to potentiate toxicity. We conclude that toxicity tests on ambient water samples containing these hydrophobic insecticides are likely to underestimate toxicity present in the field, and mimic short pulse rather than continuous exposures. Where these chemicals are of concern, the addition of PBO during testing can yield valuable information on their presence or absence. Environ Toxicol Chem 2018;37:462–472. © 2017 SETAC
Evaluation and hydrologic validation of TMPA satellite precipitation product downstream of the Pearl River Basin, China
Authors: Wang Zhaoli , Zhong Ruida , Lai Chengguang
Published: September 2017

With high spatio‐temporal resolution and wide coverage, satellite‐based precipitation products can potentially fill the deficiencies of traditional in situ gauge precipitation observations and provide an alternative data source for ungauged areas. However, due to the relatively poor accuracy and high uncertainty of satellite‐based precipitation products, it remains necessary to assess the quality and applicability of the products for each investigated area. This study evaluated the accuracy and error of the latest Tropical Rainfall Measuring Mission Multi‐satellites Precipitation Analysis 3B42‐V7 satellite‐based precipitation product and validated the applicability of the product for the Beijiang and Dongjiang River Basins, downstream of the Pearl River Basin in China. The study first evaluated the accuracy, error, and bias of the 3B42‐V7 product during 1998–2006 at daily and monthly scale via comparison with in situ observations. The study further validated the applicability of the product via hydrologic simulation using the variable infiltration capacity hydrological model for three hydrological stations in the Beijiang River Basin, considering two scenarios: a streamflow simulation with gauge‐calibrated parameters (Scenario I) and a simulation after recalibration with the 3B42‐V7 product (Scenario II). The results revealed that (a) the 3B42‐V7 product produced acceptable accuracy both at the daily scale and high accuracy at the monthly scale while generally tending to overestimate precipitation; (b) the product clearly overestimated the frequency of no rainfall events at the grid cell scale and light rainfall (<1 mm/day) events at the region scale and also overestimated the amount of heavy rain (25–50 mm/day) and hard rain (≥50 mm/day) events; (c) under Scenario I, the 3B42‐V7 product performed poorly at three stations with gauge‐calibrated parameters; under Scenario II, the recalibrated model provided significantly improved performance of streamflow simulation with the 3B42‐V7 product; (d) the variable infiltration capacity model has the ability to reveal the hydrological characteristics of the karst landform in the Beijiang Basin when using the 3B42‐V7 product.
A Monte Carlo evaluation of masked visual analysis in response‐guided versus fixed‐criteria multiple‐baseline designs
Authors: Ferron John M. , Joo Seang‐Hwane , Levin Joel R.
Published: September 2017

We developed masked visual analysis (MVA) as a structured complement to traditional visual analysis. The purpose of the present investigation was to compare the effects of computer‐simulated MVA of a four‐case multiple‐baseline (MB) design in which the phase lengths are determined by an ongoing visual analysis (i.e., response‐guided) versus those in which the phase lengths are established a priori (i.e., fixed criteria). We observed an acceptably low probability (less than .05) of false detection of treatment effects. The probability of correctly detecting a true effect frequently exceeded .80 and was higher when: (a) the masked visual analyst extended phases based on an ongoing visual analysis, (b) the effects were larger, (c) the effects were more immediate and abrupt, and (d) the effects of random and extraneous error factors were simpler. Our findings indicate that MVA is a valuable combined methodological and data‐analysis tool for single‐case intervention researchers.
The effect of ventricular assist device‐associated biomaterials on human blood leukocytes
Authors: Radley Gemma , Pieper Ina Laura , Thornton Catherine A.
Published: September 2017

Ventricular assist devices (VADs) are an effective bridging or destination therapy for patients with advanced stage heart failure. These devices remain susceptible to adverse events including infection, bleeding, and thrombus; events linked to the foreign body response. Therefore, the biocompatibility of all biomaterials used is crucial to the success of medical devices. Biomaterials common in VADs—DLC: diamond‐like carbon coated stainless steel; Sap: single‐crystal sapphire; SiN: silicon nitride; Ti: titanium alloy; and ZTA: zirconia‐toughened alumina—were tested for their biocompatibility through incubation with whole human blood for 2 h with mild agitation. Blood was then removed and used for: complete cell counts; leukocyte activation and death, and the production of key inflammatory cytokines. All were compared to time 0 and an un‐exposed 2 h sample. Monocyte numbers were lower after exposure to DLC, SiN, and ZTA and monocytes showed evidence of activation with DLC, Sap, and SiN. Neutrophils and lymphocytes were unaffected. This approach allows comprehensive analysis of the potential blood damaging effects of biomaterials. Monocyte activation by DLC, Sap, ZTA, and SiN warrants further investigation linking effects on this cell type to unfavorable inflammatory/thrombogenic responses to VADs and other blood handling devices. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1730–1738, 2018.
Injectable thermosensitive alginate/β‐tricalcium phosphate/aspirin hydrogels for bone augmentation
Authors: Fang Xiaoqian , Lei Lei , Jiang Ting , Chen Ying , Kang Yunqing
Published: September 2017

In this study, an injectable and thermo‐sensitive alginate/β‐tricalcium phosphate hydrogel (TSAH/β‐TCP) was prepared for aspirin release to a bone defect. Aspirin was dissolved into a mixture of poly(N‐isopropylacrylamide) (PNIPAAm), an aminated alginate‐g‐PNIPAAm co‐polymer, and β‐TCP powders. Scanning electron microscopy showed that TSAH/β‐TCP had an interconnected porous microstructure with a porosity of 86.78%. The cross‐linked hydrogel released approximately 40% of the aspirin in the first 3 days and then slowly released the remainder. At a low concentration (≤100 μg/mL), aspirin did not promote cell proliferation, but enhanced the alkaline phosphatase activity, and osteocalcin (OCN) and collagen I expression of human bone marrow‐derived mesenchymal stem cells. The TSAH/β‐TCP/aspirin hydrogel was injected into the periosteum of the rat cranial bone, and its in vivo bone‐forming ability was evaluated at 12 weeks. A bone morphogenetic protein 2 (BMP‐2)‐loaded TSAH/β‐TCP hydrogel was injected as a control. Micro‐computed tomography showed that the percentage of mineralized tissue in the TSAH/β‐TCP/BMP‐2 and TSAH/β‐TCP/aspirin groups were similar and significantly higher than that in the TSAH/β‐TCP group. Immunohistochemical staining showed considerable expression of OCN, especially in the TSAH/β‐TCP/BMP‐2 and TSAH/β‐TCP/aspirin groups. These results suggest that the injectable TSAH/β‐TCP/aspirin hydrogel has great potential for bone regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1739–1751, 2018.
Exploring the interaction between Mycobacterium tuberculosis enolase and human plasminogen using computational methods and experimental techniques
Authors: Rahi Amit , Dhiman Alisha , Singh Damini , Lynn Andrew M. , Rehan Mohd , Bhatnagar Rakesh
Published: September 2017

Surface localized microbial enolases’ binding with human plasminogen has been increasingly proven to have an important role in initial infection cycle of several human pathogens. Likewise, surface localized Mycobacterium tuberculosis (Mtb) enolase also binds to human plasminogen, and this interaction may entail crucial consequences for granuloma stability. The current study is the first attempt to explore the plasminogen interacting residues of enolase from Mtb. Beginning with the structural modeling of Mtb enolase, the binding pose of Mtb enolase and human plasminogen was predicted using protein‐protein docking simulations. The binding pose revealed the interface region with interacting residues and molecular interactions. Next, the interacting residues were refined and ranked by using various criteria. Finally, the selected interacting residues were tested experimentally for their involvement in plasminogen binding. The two consecutive lysine residues, Lys‐193 and Lys‐194, turned out to be active residues for plasminogen binding. These residues when substituted for alanine along with the most active residue Lys‐429, that is, the triple mutant (K193A + K194A + K429A) Mtb enolase, exhibited 40% reduction in plasminogen binding. It is worth noting that Mtb enolase lost nearly half of the plasminogen binding activity with only three simultaneous substitutions, without any significant secondary structure perturbation. Further, the sequence comparison between Mtb and human enolase isoforms suggests the possibility of selective targeting of Mtb enolase to obstruct binding of human plasminogen.
SIRT1 deacetylates KLF4 to activate Claudin‐5 transcription in ovarian cancer cells
Authors: Zhang Xinjian , Chen Junliang , Sun Lina , Xu Yong
Published: September 2017

Malignant cancers are distinguished from more benign forms of cancers by enhanced ability to disseminate. A number of factors aid the migration and invasion of malignant cancer cells. Epithelial‐to‐mesenchymal transition (EMT), which greatly facilitates the dissemination of cancer cells, is characterized by the loss of epithelial markers and the acquisition of mesenchymal markers thereby rendering the cells more migratory and invasive. We have previously shown that the class III lysine deacetylase SIRT1 plays a critical role curbing the metastasis of ovarian cancer cells partly by blocking EMT. Here we investigated the mechanism by which SIRT1 regulates the transcription of Claudin 5 (CLDN5), an epithelial marker gene, in ovarian cancer cells. SIRT1 activation or over‐expression up‐regulated CLDN5 expression while SIRT1 inhibition or depletion down‐regulated CLDN5 expression. SIRT1 interacted with and deacetylated Kruppel‐like factor 4 (KLF4), a known transcriptional activator for CLDN5. Deacetylation by SIRT1 promoted nuclear accumulation of KLF4 and enhanced the binding of KLF4 to the CLDN5 promoter in the nucleus. SIRT1‐mediated up‐regulation of CLDN5 was abrogated in the absence of KLF4. In accordance, KLF4 depletion by siRNA rendered ovarian cancer cells more migratory and invasive despite of SIRT1 activation or over‐expression. In conclusion, our data suggest that SIRT1 activates CLDN5 transcription by deacetylating and potentiating KLF4.
Children's experiences and perceptions of street culture, parental supervision, and parental mediation in an urban neighborhood
Authors: van Dijken Maartje , Stams Geert‐Jan , de Winter Micha
Published: September 2017

Local street cultures may appear more or less “extreme,” depending on several contextual factors. Using focus groups, the current study aimed to explore what children, aged 7 to 12 years, think of the assumption that parents play an important role on the street to increase safety in the public domain. Involvement of parents can either be helpful or contribute to escalation of the conflict. Children's biggest concern was that parents are not able to be neutral or that children did not know the parent who intervened. They can imagine intervening being helpful when the intervening parents are known and trusted. We expect that when the public environment is safe and social cohesion is strong, the amount of conflicts will reduce and the help of parents will be generally accepted. We expect that increasing public familiarity and strengthening social control in disadvantaged neighborhoods can further limit the negative influences of street culture.
Understanding the influence of resilience for people with a lived experience of mental illness: A self‐determination theory perspective
Authors: Perlman Dana , Patterson Christopher , Moxham Lorna , Taylor Ellie K. , Brighton Renee , Sumskis Susan , Heffernan Tim
Published: September 2017

Behaviors associated with resilience can be seen as tantamount to coping with stress and vulnerability. This is important for people who live with mental illness. This study aimed to determine whether key basic psychological needs influence resilience among people with a lived experience of mental illness. A total of 159 consumers with a lived experience of mental illness completed self‐report surveys measuring resilience and the basic psychological needs (autonomy, competence, and relatedness) espoused in self‐determination theory. A 2‐step analysis was conducted, including Pearson product correlations and stepwise multiple regression. Higher levels of relatedness significantly predicted resilience. Competence and autonomy did not have a significant influence on resilience. Reconnecting or establishing social relationships within ones community is important for people living with mental illness. The link between resilience and relatedness ought to be considered in treatment plans.
Involvement of nutrients and nutritional mediators in mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA synthase gene expression
Authors: Rescigno Tania , Capasso Anna , Tecce Mario Felice
Published: September 2017

Mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA (HMG‐CoA) synthase (HMGCS2) catalyses the first step of ketogenesis and is critical in various metabolic conditions. Several nutrient molecules were able to differentially modulate HMGCS2 expression levels. Docosahexaenoic acid (DHA, C22:6, n‐3), eicosapentaenoic acid (EPA, C20:5, n‐3), arachidonic acid (AA, C20:4, n‐6), and glucose increased HMGCS2 mRNA and protein levels in HepG2 hepatoma cells, while fructose decreased them. The effect of n‐6 AA resulted significantly higher than that of n‐3 PUFA, but when combined all these molecules were far less efficient. Insulin reduced HMGCS2 mRNA and protein levels in HepG2 cells, even when treated with PUFA and monosaccharides. Several nuclear receptors and transcription factors are involved in HMGCS2 expression regulation. While peroxysome proliferator activated receptor α (PPAR‐α) agonist WY14643 increased HMGCS2 expression, this treatment was unable to affect PUFA‐mediated regulation of HMGCS2 expression. Forkhead box O1 (FoxO1) inhibitor AS1842856 reduced HMGCS2 expression and suppressed induction promoted by fatty acids. Cells treatment with liver X receptor alpha (LXRα) agonist T0901317 reduced HMGCS2 mRNA, indicating a role for this transcription factor as suppressor of HMGCS2 gene. Previous observations already indicated HMGCS2 expression as possible nutrition status reference: our results show that several nutrients as well as specific nutritional related hormonal conditions are able to affect significantly HMGCS2 gene expression, indicating a relevant role for PUFA, which are mostly derived from nutritional intake. These insights into mechanisms of its regulation, specifically through nutrients commonly associated with disease risk, indicate HMGCS2 expression as possible reference marker of metabolic and nutritional status.
Gap junctional intercellular communication in adipose‐derived stromal/stem cells is cell density‐dependent and positively impacts adipogenic differentiation
Authors: Wiesner Miriam , Berberich Oliver , Hoefner Christiane , Blunk Torsten , Bauer‐Kreisel Petra
Published: September 2017

Adipose‐derived stromal/stem cells (ASCs) represent a widely used cell source with multi‐lineage differentiation capacity in approaches for tissue engineering and regenerative medicine. Despite the multitude of literature on their differentiation capacity, little is reported about the physiological properties contributing to and controlling the process of lineage differentiation. Direct intercellular communication between adjacent cells via gap junctions has been shown to modulate differentiation processes in other cell types, with connexin 43 (Cx43) being the most abundant isoform of the gap junction‐forming connexins. Thus, in the present study we focused on the expression of Cx43 and gap junctional intercellular communication (GJIC) in human ASCs, and its significance for adipogenic differentiation of these cells. Cx43 expression in ASCs was demonstrated histologically and on the gene and protein expression level, and was shown to be greatly positively influenced by cell seeding density. Functionality of gap junctions was proven by dye transfer analysis in growth medium. Adipogenic differentiation of ASCs was shown to be also distinctly elevated at higher cell seeding densities. Inhibition of GJIC by 18α‐glycyrrhetinic acid (AGA) significantly compromised adipogenic differentiation, as demonstrated by histology, triglyceride quantification, and adipogenic marker gene expression. Flow cytometry analysis showed a lower proportion of cells undergoing adipogenesis when GJIC was inhibited, further indicating the importance of GJIC in the differentiation process. Altogether, this study demonstrates the impact of direct cell–cell communication via gap junctions on the adipogenic differentiation process of ASCs, and may contribute to further integrate direct intercellular crosstalk in rationales for tissue engineering approaches.
Blunting of estrogen modulation of cardiac cellular chymase/RAS activity and function in SHR
Authors: Ahmad Sarfaraz , Sun Xuming , Lin Marina , Varagic Jasmina , Zapata‐Sudo Gisele , Ferrario Carlos M. , Groban Leanne , Wang Hao
Published: September 2017

The relatively low efficacy of ACE‐inhibitors in the treatment of heart failure in women after estrogen loss may be due to their inability to reach the intracellular sites at which angiotensin (Ang) II is generated and/or the existence of cell‐specific mechanisms in which ACE is not the essential processing pathway for Ang II formation. We compared the metabolic pathway for Ang II formation in freshly isolated myocytes (CMs) and non‐myocytes (NCMs) in cardiac membranes extracted from hearts of gonadal‐intact and ovariectomized (OVX) adult WKY and SHR rats. Plasma Ang II levels were higher in WKY vs. SHR (strain effect: WKY: 62 ± 6 pg/ml vs. SHR: 42 ± 9 pg/ml; p < 0.01), independent of OVX. The enzymatic activities of chymase, ACE, and ACE2 were higher in NCMs versus CMs, irrespective of whether assays were performed in cardiac membranes from WKY or SHR or in the presence or absence of OVX. E2 depletion increased chymase activity, but not ACE activity, in both CMs and NCMs. Moreover, cardiac myocyte chymase activity associated with diastolic function in WKYs and cardiac structure in SHRs while no relevant functional and structural relationships between the classic enzymatic pathway of Ang II formation by ACE or the counter‐regulatory Ang‐(1‐7) forming path from Ang II via ACE2 were apparent. The significance of these novel findings is that targeted cell‐specific chymase rather than ACE inhibition may have a greater benefit in the management of HF in women after menopause.
In between mental evolution and unconscious memory: Lamarckism, Darwinism, and professionalism in late Victorian Britain
Authors: Turbil Cristiano
Published: September 2017

In 1884 Samuel Butler published a collection of essays entitledRemarks on George Romanes’ Mental Evolution, where he attempted to show how Romanes’ idea of mental evolution presented similarities with his theory of unconscious memory. By looking at Romanes’ work through Butler’s writing, this article will reevaluate some aspects of their works regarding the complex debate about memory, heredity, and instinct. This paper will explore the main differences and similarities between Romanes’ science and Butler’s writing on science both in terms of their ideas and contents. It will then look into their different professional relationships with Darwin and how this determined the professional and public reception of their theories.
Role of ALDH1 in the prognosis of esophageal cancer and its relationship with tumor microenvironment
Authors: Chen Miao‐Fen , Chen Ping‐Tsung , Lu Ming‐Shian , Chen Wen‐Cheng
Published: September 2017

Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and significantly increased in cancer stem‐like cells. In the present study, the role of ALDH1 in esophageal squamous cell carcinoma (ESCC) was investigated. We retrospectively analyzed the clinical outcomes of 148 ESCC and examined its correlation with ALDH1 levels. Furthermore, we preformed cellular and animal experiments to investigate the role of ALDH1 in tumor progression and microenvironment. Our data revealed that ALDH1 staining was positively linked to a higher clinical stage, higher loco‐regional failure rate, and shorter survival time. Furthermore, there was a positive link between ALDH1 expression and IL‐6 signaling according to the data of clinical specimens and cellular experiments. Using animal model, ALDH1‐positive tumors were associated with aggressive tumor growth, increased IL‐6, augmented epithelial‐mesenchymal transition (EMT), and activation of myeloid‐derived suppressor cells (MDSCs). Blockade of COX‐2 attenuated the aggressive tumor growth of ALDH1‐positive cancer cells. In conclusion, our findings suggested that ALDH1 played an important role in tumor aggressiveness and associated with a tumor‐promoting microenvironment in esophageal cancer. Directly targeting ALDH1 or using a COX‐2 inhibitor could be a promising strategy for the treatment of ESCC.
Tremor in Dystonia: A Cross‐sectional Study from India
Authors: Pandey Sanjay , Sarma Neelav
Published: September 2017

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Background

Tremor is an important phenotypic motor feature in dystonia, but there is limited literature regarding its prevalence and phenomenology.

Methods

This cross‐sectional study included 90 patients with adult‐onset, isolated dystonia from a tertiary care movement disorder center in India. Patients were assessed for tremor in the head and in different body parts. Surface electromyography studies of tremor were recorded of the involved limb in different positions.

Results

Tremor was present in 41 patients (45.55%) who had dystonia, including 21 of 41 patients (51.21%) with cervical dystonia, 15 of 34 (44.11%) with limb dystonia, and 5 of 15 (33.33%) with cranial dystonia. Significantly later age at presentation (47.19 ± 14.55 years vs. 40.39 ± 13.74 years; P = 0.012) and longer disease duration (5.11 ± 5.85 years vs. 2.60 ± 2.57 years; P = 0.004) were observed in patients with versus without tremor. Upper limb tremor was present in 33 patients, head tremor was present in 14, and leg tremor was present in 2. Tremor was present in 17 of 25 patients (68%) with segmental dystonia and in 6 of 9 (66.66%) with multifocal dystonia. Tremor was least frequent in patients with focal dystonia (18 of 56 patients; 32.14%).

Conclusions

Tremor was common (>45%) in patients with primary adult‐onset dystonia. Patients who had tremor were older and had a longer duration of symptoms. Patients with segmental and multifocal dystonia had more tremor than those with focal dystonia. In contrast to some other studies, the current patients had more upper limb tremor than head tremor, and a combination of dystonic tremor and tremor associated with dystonia was more common than isolated dystonic tremor.
Smartphone Apps Provide a Simple, Accurate Bedside Screening Tool for Orthostatic Tremor
Authors: Bhatti Danish , Thompson Rebecca , Hellman Amy , Penke Cynthia , Bertoni John M , Torres‐Russotto Diego
Published: September 2017

Background

Orthostatic Tremor (OT) is characterized by the presence of a sensation of instability while standing, associated with high frequency (13–18 Hz) lower extremity tremor. Diagnosis is confirmed with surface electromyography (EMG). An accurate screening tool that could be used in the routine clinical setting, without any specialized equipment, would be useful in earlier detection of OT and judicial use of additional testing.

Objective

The objective of this study was to evaluate OT diagnostic test characteristics at bedside using iPhone's built‐in accelerometer and available applications for tremor recordings.

Methods

We obtained recordings using iPhones (Model 5, 5s, and 6) and free Applications (“LiftPulse” by LiftLabs [App1] and “iSeismometer” by ObjectGraph LLC [App2]) at default settings.

Results

24 EMG‐confirmed OT subjects (mostly females, 22/24) and 15 age‐matched controls (mostly males, 11/15) were evaluated. App1 detected OT range tremor in 22/24 patients and none of the controls. (Sensitivity = 92%, Specificity = 100%, NPV = 88%). App2 detected OT range tremor in 21/24 patients and in 1/13 controls (Sensitivity = 88%, Specificity = 92%, NPV = 80%). When combined, 24/24 patients and 1/13 controls had OT range tremor (Sensitivity = 100%, Specificity = 92%, NPV = 100%).

Conclusions

Smartphone apps that use the built‐in accelerometer provide a simple, accurate and inexpensive bedside screening diagnostic tool for patients with OT.
Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy
Authors: Obeso J.A. , Stamelou M. , Goetz C.G. , Poewe W. , Lang A.E. , Weintraub D. , Burn D. , Halliday G.M. , Bezard E. , Przedborski S. , Lehericy S. , Brooks D.J. , Rothwell J.C. , Hallett M. , DeLong M.R. , Marras C. , Tanner C.M. , Ross G.W. , Langston J.W. , Klein C. , Bonifati V. , Jankovic J. , Lozano A.M. , Deuschl G. , Bergman H. , Tolosa E. , Rodriguez‐Violante M. , Fahn S. , Postuma R.B. , Berg D. , Marek K. , Standaert D.G. , Surmeier D.J. , Olanow C.W. , Kordower J.H. , Calabresi P. , Schapira A.H.V. , Stoessl A.J.
Published: September 2017

This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple‐author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state‐of‐the‐art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society
Characterization of Wild Blueberry Polyphenols Bioavailability and Kinetic Profile in Plasma over 24‐h Period in Human Subjects
Authors: Zhong Siqiong , Sandhu Amandeep , Edirisinghe Indika , Burton‐Freeman Britt
Published: September 2017

Scope

Understanding the metabolic fate of polyphenols from plant foods can aid in developing dietary recommendations that maximize their health benefits. Wild blueberries (WBB) provide a distinctive composition of dietary anthocyanins and chlorogenic acid (CGA).

Methods and results

This is a single blind, randomized, two‐arm crossover controlled study. Human subjects ingested a WBB beverage (25 g freeze dried WBB powder) or placebo beverage with a meal and plasma was collected over 24 h. Anthocyanins, CGA and their metabolites were characterized and quantified in beverages and in plasma using targeted and non‐targeted mass analyses. Bioavailability of WBB anthocyanins and 3‐CGA was 1.1 and 0.2%, respectively. Parent anthocyanins and 3‐CGA peaked ≈2 h post ingestion, while phase II metabolites, including glucuronide conjugates of peonidin, delphinidin, cyanidin and petunidin peaked ≈ 2.6, 6.3, 7 and 8.8 h, respectively. Phenolic acids (metabolites) peaked between 0.5 and 24 h. Biphasic responses were evident suggesting preferential enterohepatic recycling for some compounds.

Conclusion

The data indicate bioavailability of early and late phase WBB metabolites peaking at different times during the 24 h period, which may be important for maximizing their biological activity.
Characterization of proton pencil beam scanning and passive beam using a high spatial resolution solid‐state microdosimeter
Authors: Tran Linh T. , Chartier Lachlan , Bolst David , Pogossov Alex , Guatelli Susanna , Petasecca Marco , Lerch Michael L. F. , Prokopovich Dale A. , Reinhard Mark I. , Clasie Benjamin , Depauw Nicolas , Kooy Hanne , Flanz Jacob B. , McNamara Aimee , Paganetti Harald , Beltran Chris , Furutani Keith , Perevertaylo Vladimir L. , Jackson Michael , Rosenfeld Anatoly B.
Published: September 2017

Purpose

This work aims to characterize a proton pencil beam scanning (PBS) and passive double scattering (DS) systems as well as to measure parameters relevant to the relative biological effectiveness (RBE) of the beam using a silicon on insulator (SOI) microdosimeter with well‐defined 3D sensitive volumes (SV). The dose equivalent downstream and laterally outside of a clinical PBS treatment field was assessed and compared to that of a DS beam.

Methods

A novel silicon microdosimeter with well‐defined 3D SVs was used in this study. It was connected to low noise electronics, allowing for detection of lineal energies as low as 0.15 keV/μm. The microdosimeter was placed at various depths in a water phantom along the central axis of the proton beam, and at the distal part of the spread‐out Bragg peak (SOBP) in 0.5 mm increments. The RBE values of the pristine Bragg peak (BP) and SOBP were derived using the measured microdosimetric lineal energy spectra as inputs to the modified microdosimetric kinetic model (MKM). Geant4 simulations were performed in order to verify the calculated depth‐dose distribution from the treatment planning system (TPS) and to compare the simulated dose‐mean lineal energy to the experimental results.

Results

For a 131 MeV PBS spot (124.6 mm R90 range in water), the measured dose‐mean lineal energy increased from 2 keV/μm at the entrance to 8 keV/μm in the BP, with a maximum value of 10 keV/μm at the distal edge. The derived RBE distribution for the PBS beam slowly increased from 0.97 ± 0.14 at the entrance to 1.04 ± 0.09 proximal to the BP, then to 1.1 ± 0.08 in the BP, and steeply rose to 1.57 ± 0.19 at the distal part of the BP. The RBE distribution for the DS SOBP beam was approximately 0.96 ± 0.16 to 1.01 ± 0.16 at shallow depths, and 1.01 ± 0.16 to 1.28 ± 0.17 within the SOBP. The RBE significantly increased from 1.29 ± 0.17 to 1.43 ± 0.18 at the distal edge of the SOBP.

Conclusions

The SOI microdosimeter with its well‐defined 3D SV has applicability in characterizing proton radiation fields and can measure relevant physical parameters to model the RBE with submillimeter spatial resolution. It has been shown that for a physical dose of 1.82 Gy at the BP, the derived RBE based on the MKM model increased from 1.14 to 1.6 in the BP and its distal part. Good agreement was observed between the experimental and simulation results, confirming the potential application of SOI microdosimeter with 3D SV for quality assurance in proton therapy.
Iterative volume of interest based 4D cone‐beam CT
Authors: Martin Rachael , Ahmad Moiz , Hugo Geoffrey , Pan Tinsu
Published: September 2017

Purpose

4D cone‐beam CT (CBCT) has potential applications in soft tissue alignment and tumor motion verification at the time of radiation treatment. However, prominent streak artifacts with conventional image reconstructions have limited its clinical use and alternative reconstructions are generally too computationally expensive for the time available. We propose an iterative volume of interest based (I4D VOI) reconstruction technique, where 4D reconstruction is only performed within a VOI, to limit streak artifacts with limited added computation time.

Methods

The I4D VOI technique is compared to standard cone‐beam filtered back projection (FDK), an FDK VOI technique, and unconstrained total variation (TV) minimization by comparing tumor motion quantification errors and image quality. 14 long CBCT scans (6.5 to 12 min) of patients receiving radiation treatment for lung cancer were used for the comparison. Rigid registration between phase images of FDK reconstructions using all projections were used to quantify the gold standard motion. Projections were removed to simulate 2 minute scans and these new projection sets were used for each of the test reconstructions.

Results

Excluding two patients where registration failed, the average root mean square (RMS) error for each method was as follows: 1.5 ± 0.2 mm for FDK, 1.4 ± 0.2 mm for FDK VOI, 1.3 ± 0.2 mm for I4D VOI, 1.7 ± 0.4 mm for low regularization TV minimization, and 1.1 ± 0.2 mm for high regularization TV minimization. No significant difference was observed between RMS error for I4D VOI and the other methods, except for unsmoothed FDK VOI (P = 0.02). An increase in RMS error difference between I4D VOI and smoothed FDK VOI was observed going from 2 min to 1 min scans (0.1 mm to 0.3 mm, P = 0.20 to P = 0.09).

Conclusions

I4D VOI and FDK VOI reconstruction measured tumor trajectories with equivalent accuracy as TV minimization with improved bony anatomy image quality and computation time (I4D VOI was approximately 15 and 95 times faster than low and high regularization TV minimization, respectively). Within the VOI, streak artifact reduction compared to FDK VOI may be beneficial for tumor visualization and motion measurement, but requires further study.
Using Public Data for Comparative Proteome Analysis in Precision Medicine Programs
Authors: Hughes Christopher S. , Morin Gregg B.
Published: September 2017

Purpose

Maximizing the clinical utility of information obtained in longitudinal precision medicine programs would benefit from robust comparative analyses to known information to assess biological features of patient material toward identifying the underlying features driving their disease phenotype. Herein, the potential for utilizing publically deposited mass‐spectrometry‐based proteomics data to perform inter‐study comparisons of cell‐line or tumor‐tissue materials is investigated.

Experimental design

To investigate the robustness of comparison between MS‐based proteomics studies carried out with different methodologies, deposited data representative of label‐free (MS1) and isobaric tagging (MS2 and MS3 quantification) are utilized.

Results

In‐depth quantitative proteomics data acquired from analysis of ovarian cancer cell lines revealed the robust recapitulation of observable gene expression dynamics between individual studies carried out using significantly different methodologies. The observed signatures enable robust inter‐study clustering of cell line samples. In addition, the ability to classify and cluster tumor samples based on observed gene expression trends when using a single patient sample is established. With this analysis, relevant gene expression dynamics are obtained from a single patient tumor, in the context of a precision medicine analysis, by leveraging a large cohort of repository data as a comparator.

Conclusion and Clinical Relevance

Together, these data establish the potential for state‐of‐the‐art MS‐based proteomics data to serve as resources for robust comparative analyses in precision medicine applications.
The interactions between gut microbiota and entomopathogenic fungi: a potential approach for biological control of Blattella germanica (L.)
Authors: Zhang Fan , Sun Xiao X , Zhang Xian C , Zhang Shuo , Lu Jie , Xia Yong M , Huang Yan H , Wang Xue J
Published: September 2017

BACKGROUND

Metarhizium anisopliae and Beauveria bassiana mainly infect insects through the cuticle; gut infection occasionally occurs. Micro‐organisms existing in the gut may play a crucial role in the evolution and ecology of host defenses against fungal pathogens. To evaluate whether the gut bacteria participate in antifungal activity, and to determine their role in host protection, the interactions between gut bacteria and M. anisopliae and the diversity of gut microbiota in cockroaches were studied.

RESULTS

An oral feeding test showed that the mortality of conventional cockroaches was significantly lower than that of germ‐free cockroaches; both gut homogenates and aqueous fecal extracts showed antifungal activity, but the samples from germ‐free cockroaches did not. Twenty‐two bacterial strains with antifungal activity and siderophore‐producing ability were isolated from the gut and feces of cockroaches. Using high‐throughput sequencing techniques, a total of 23 different phyla and 212 genera were detected. The composition of the microbiota of the hindgut was vastly different from those of the foregut and midgut; higher diversity and abundance of Bacteroides and Pseudomonas were found in the hindgut.

CONCLUSION

The gut microbiota of German cockroaches may play a critical role in protecting cockroaches from fungal invasion and colonization. Removing certain bacteria from the B. germanica microbiota may facilitate microbial control using fungal pathogens. © 2017 Society of Chemical Industry
The impact of horizontal resolution and ensemble size for convective‐scale probabilistic forecasts
Authors: Raynaud Laure , Bouttier François
Published: September 2017

The relative benefits of ensemble size and model resolution are investigated within the AROME–France convective‐scale ensemble prediction system (EPS), which operationally runs 12 perturbed members at 2.5 km horizontal resolution. This baseline configuration is compared with two auxiliary ensemble experiments, which are run at resolutions of 2.5 and 1.3 km, with 34 and 12 members respectively. In addition, post‐processing techniques including neighbourhood approaches and time‐lagging are examined as potential alternatives to increase the sample size at a lower computational cost.

Probabilistic verification of the raw EPS outputs indicates that increasing model resolution is more beneficial at very short ranges, whereas increasing the ensemble size has a larger impact at longer forecast ranges, as predictability decreases and more members are required to sample the larger uncertainty better. The neighbourhood processing confirms these conclusions and is shown to improve precipitation forecasts of all EPS configurations significantly, especially the smaller‐size ensembles. Hence, it can be considered as a viable substitute to running additional AROME members for the first 24 h of forecasts.

Time‐lagging of three successive ensemble productions also appears to be a competitive approach to improve the ensemble forecast skill, particularly at very short ranges, where AROME‐EPS is known to be underdispersive. The performance of the time‐lagged 36 member ensemble is generally close to or even better than the performance of the single 34 member ensemble for the whole forecast range and for different surface weather variables.

Overall, given the relative costs and skills of the different EPS configurations, we suggest that resources should primarily be spent on increasing ensemble size, by combining both additional members and post‐processing methods. In addition, the performance of the 1.3 km ensemble should be examined further for explicit high‐impact weather and with an appropriate tuning of physics and surface perturbations.
Government Accountability and Natural Disasters: The Impact of Natural Hazard Events on Political Trust and Satisfaction With Governments in Europe
Authors: Albrecht Frederike
Published: September 2017

Do natural disasters generally affect individuals’ political trust and satisfaction with the government? To answer this question, 10 cases of minor and major disasters in Europe are examined using a quasi‐experimental quantitative design that is based on ordinary least squares regression models. The results indicate that alterations in satisfaction with the government are possible, but only occur in very specific instances, and that effects are small. Changes in political trust are even more unlikely. While it was expected that disasters and their management have at least some effect on how individuals perceive their government's performance because they hold incumbents accountable for their actions, generally speaking this effect hardly occurs in relation to natural disasters. Political attitudes among individuals appear largely unaffected and cases of disasters when incumbents benefit from or are blamed for the perceived management of disasters appear to be uncommon.
Toward a process theory of entrepreneurial ecosystems
Authors: Spigel Ben , Harrison Richard
Published: September 2017

Research Summary: Entrepreneurial ecosystems have recently emerged as a popular concept within entrepreneurship policy and practitioner communities. Specifically, they are seen as a regional economic development strategy that is based around creating supportive environments that foster innovative start‐ups. However, existing research on entrepreneurial ecosystems has been largely typological and atheoretical and has not yet explored how they influence the entrepreneurship process. This article critically examines the relationships between ecosystems and other existing literatures such as clusters and regional innovation systems. Drawing on this background, the article suggests that a process‐based view of ecosystems provides a better framework to understand their role in supporting new venture creation. This framework is used to explain the evolution and transformation of entrepreneurial ecosystems and to create a typology of different ecosystem structures.

Managerial Summary: Entrepreneurial ecosystems are a new buzzword within research and managerial circles. They represent the types of cultural, social, economic, and political environments within a region that support high‐growth entrepreneurship. But current research does little more than look at successful ecosystems to identify best practices. This article examines what we know about entrepreneurial ecosystems and links them with existing theories like clusters and regional innovation systems. We argue that successful and unsuccessful entrepreneurship within an ecosystem generates critical entrepreneurial resources like investment capital, skilled workers, and entrepreneurial knowledge. This, in turn, supports future high‐growth venture creation. The types of resources available in an ecosystem and the ability of these resources to flow through social networks helps separate strong, well‐functioning ecosystems from weak, poorly functioning ones.
On the relationship between inequality and entrepreneurship
Authors: Packard Mark D. , Bylund Per L.
Published: September 2017

Research Summary

We reexamine and explore the modern view of inequality against entrepreneurial market process theories, which leads us to three key assertions. First, we question the validity of income inequality as a proxy for true inequality (i.e., inequality of individual well‐being), observing nonlinearity between the two constructs. Second, we explore the entrepreneurial microfoundations of growing and shrinking inequality in market societies, arguing that individual inequality is primarily the outcome of abnormal gains from disequilibrating creative destructive processes. These shifts are temporary, however, as equilibrating (arbitraging) entrepreneurship competes away monopoly profits. Growing inequality trends, then, are seen primarily as the result of increasingly large, but also shorter, waves of creative destruction. Finally, we reconsider the issue of the injustice of inequality through this market process lens.

Managerial summary

We contribute three arguments to the debate over economic inequality. We are (or ought to be) concerned over differences in individual well‐being, not income. Studies of income inequality can be misleading. We argue that a key and so far overlooked source of economic inequality is entrepreneurship. Disruptive entrepreneurship (via innovation) redistributes economic resources away from the present industry, reallocating them in a more unequal redistribution, with the successful disruptor capturing an unequal share of resources. Imitative entrepreneurship, however, tends to mitigate this inequality, competing away abnormal profits while expanding new products’ diffusion among consumers. Finally, we observe that economic inequality may not be as unjust as previously thought, and we caution against corrective policy that might inhibit entrepreneurship.
Opportunity creation: Entrepreneurial agency, interaction, and affect
Authors: Goss David , Sadler‐Smith Eugene
Published: September 2017

Research Summary: This article addresses opportunity creation, with particular focus on the interplay between social context and individual agency. Using ideas grounded in contemporary micro‐sociology, we offer a conceptual framework that articulates opportunity‐creating agency as the outcome of socially situated subjectivity, supportive or challenging interactions, and the circulation of emotional energy. This dynamic process is illustrated with references to entrepreneur Sir Richard Branson (founder of Virgin). Our article contributes to opportunity creation research by: offering a conception of individual opportunity‐creating propensities rooted in social situations and consistent with constructionist assumptions; specifying the role played by affect/emotion in opportunity creation and positing a novel creative role for negative affect; and connecting opportunity creation with other areas of theoretical interest in entrepreneurship, such as creativity, frustration, and hubris.

Managerial summary: This article examines how social relationships and emotions can together influence the ways entrepreneurs initiate and shape opportunities. Using examples from the career of Sir Richard Branson (founder of Virgin), we suggest ways in which the emotional intensity of social interactions can motivate entrepreneurs to act decisively to initiate opportunities for business formation and development. We suggest how this may help us understand not just opportunity creation, but also key entrepreneurial issues, such as creativity, frustration, and hubris.