bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining the optimal human reliability analysis (HRA) method in healthcare systems using Fuzzy ANP and Fuzzy TOPSIS
Authors: Abbaspour Asghar , Saremi Mahnaz , Alibabaei Ahmad , Moghanlu Pedram S
Published: January 2020

Purpose

As one of the leading causes of deaths and injuries, medical errors constitute a veritable threat to patient safety. Despite this fact, no unique method has yet been established to identify and evaluate medical errors. This study was conducted to select an optimal human reliability analysis method compatible with healthcare systems from available methods. Design/methodology/approach: In order to select the optimal method for the identification and evaluation of medical errors, different criteria and sub-criteria were determined by reviewing the literature and based on experts’ opinions. Next, weights of criteria and sub-criteria were specified by using the fuzzy analytical network process (ANP). Finally, fuzzy technique for order preference by similarity to ideal solution method was used to prioritize the methods.

Findings

Six criteria and 21 sub-criteria for choosing the optimal method were determined. The utility, usability, and structure of a method had the highest influence with weights of 0.262, 0.191, and 0.187, respectively. Based on the results of fuzzy technique for order preference by similarity to ideal solution, the Human Error Assessment and Reduction Technique method with a closeness coefficient of 0.576 was selected as the optimal method for identifying medical errors. The Human Factors Analysis and Classification System and Systematic Human Error Reduction and Prediction Approach methods ranked second and third, respectively. Originality/value: To date, no studies have attempted to determine the optimal methods for identification and assessment of medical errors. This paper aimed to fill this gap by using fuzzy analytical network process and fuzzy technique for order preference by similarity to ideal solution techniques.
Avadomide monotherapy in relapsed/refractory DLBCL: safety, efficacy, and a predictive gene classifier
Authors: Carpio Cecilia , Bouabdallah Reda , Ysebaert Loïc , Sancho Juan-Manuel , Salles Gilles , Cordoba Raul , Pinto Antonio , Gharibo Mecide , Rasco Drew , Panizo Carlos , Lopez-Martin Jose A. , Santoro Armando , Salar Antonio , Damian Silvia , Martin Alejandro , Verhoef Gregor , Van den Neste Eric , Wang Maria , Couto Suzana , Carrancio Soraya , Weng Andrew , Wang Xuehai , Schmitz Frank , Wei Xin , Hege Kristen , Trotter Matthew W. B. , Risueño Alberto , Buchholz Tonia J. , Hagner Patrick R. , Gandhi Anita K. , Pourdehnad Michael , Ribrag Vincent
Published: January 2020

Treatment options for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are limited, with no standard of care; prognosis is poor, with 4- to 6-month median survival. Avadomide (CC-122) is a cereblon-modulating agent with immunomodulatory and direct antitumor activities. This phase 1 dose-expansion study assessed safety and clinical activity of avadomide monotherapy in patients with de novo R/R DLBCL and transformed lymphoma. Additionally, a novel gene expression classifier, which identifies tumors with a high immune cell infiltration, was shown to enrich for response to avadomide in R/R DLBCL. Ninety-seven patients with R/R DLBCL, including 12 patients with transformed lymphoma, received 3 to 5 mg avadomide administered on continuous or intermittent schedules until unacceptable toxicity, disease progression, or withdrawal. Eighty-two patients (85%) experienced ≥1 grade 3/4 treatment-emergent adverse events (AEs), most commonly neutropenia (51%), infections (24%), anemia (12%), and febrile neutropenia (10%). Discontinuations because of AEs occurred in 10% of patients. Introduction of an intermittent 5/7-day schedule improved tolerability and reduced frequency and severity of neutropenia, febrile neutropenia, and infections. Among 84 patients with de novo R/R DLBCL, overall response rate (ORR) was 29%, including 11% complete response (CR). Responses were cell-of-origin independent. Classifier-positive DLBCL patients (de novo) had an ORR of 44%, median progression-free survival (mPFS) of 6 months, and 16% CR vs an ORR of 19%, mPFS of 1.5 months, and 5% CR in classifier-negative patients (P = .0096). Avadomide is being evaluated in combination with other antilymphoma agents. This trial was registered at www.clinicaltrials.gov as #NCT01421524.
High total metabolic tumor volume at baseline predicts survival independent of response to therapy
Authors: Vercellino Laetitia , Cottereau Anne-Segolene , Casasnovas Olivier , Tilly Hervé , Feugier Pierre , Chartier Loic , Fruchart Christophe , Roulin Louise , Oberic Lucie , Pica Gian Matteo , Ribrag Vincent , Abraham Julie , Simon Marc , Gonzalez Hugo , Bouabdallah Reda , Fitoussi Olivier , Sebban Catherine , López-Guillermo Armando , Sanhes Laurence , Morschhauser Franck , Trotman Judith , Corront Bernadette , Choufi Bachra , Snauwaert Sylvia , Godmer Pascal , Briere Josette , Salles Gilles , Gaulard Philippe , Meignan Michel , Thieblemont Catherine
Published: January 2020

Early identification of ultra-risk diffuse large B-cell lymphoma (DLBCL) patients is needed to aid stratification to innovative treatment. Previous studies suggested high baseline total metabolic tumor volume (TMTV) negatively impacts survival of DLBCL patients. We analyzed the prognostic impact of TMTV and prognostic indices in DLBCL patients, aged 60 to 80 years, from the phase 3 REMARC study that randomized responding patients to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) into maintenance lenalidomide or placebo. TMTV was computed on baseline positron emission tomography/computed tomography using the 41% maximum standardized uptake value method; the optimal TMTV cutoff for progression-free (PFS) and overall survival (OS) was determined and confirmed by a training validation method. There were 301 out of 650 evaluable patients, including 192 patients classified as germinal center B-cell–like (GCB)/non-GCB and MYC/BCL2 expressor. Median baseline TMTV was 238 cm3; optimal TMTV cutoff was 220 cm3. Patients with high vs low TMTV showed worse/higher Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, stage III or IV disease, >1 extranodal site, elevated lactate dehydrogenase, International Prognostic Index (IPI) 3-5, and age-adjusted IPI 2-3. High vs low TMTV significantly impacted PFS and OS, independent of maintenance treatment. Although the GCB/non-GCB profile and MYC expression did not correlate with TMTV/survival, BCL2 >70% impacted PFS and could be stratified by TMTV. Multivariate analysis identified baseline TMTV and ECOG PS as independently associated with PFS and OS. Even in responding patients, after R-CHOP, high baseline TMTV was a strong prognosticator of inferior PFS and OS. Moreover, TMTV combined with ECOG PS may identify an ultra-risk DLBCL population. This trial was registered at www.clinicaltrials.gov as #NCT01122472.
Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study
Authors: Sanchorawala Vaishali , Sarosiek Shayna , Schulman Amanda , Mistark Meredith , Migre Mary Ellen , Cruz Ramon , Sloan J. Mark , Brauneis Dina , Shelton Anthony C.
Published: January 2020

Daratumumab, a monoclonal CD38 antibody, is approved in the treatment of myeloma, but its efficacy and safety in light-chain (AL) amyloidosis has not been formally studied. This prospective phase 2 trial of daratumumab monotherapy for the treatment of AL amyloidosis was designed to determine the safety, tolerability, and hematologic and clinical response. Daratumumab 16 mg/kg was administered by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter until progression or unacceptable toxicity, for up to 24 months. Twenty-two patients with previously treated AL amyloidosis were enrolled. The majority of the patients had received high-dose melphalan and stem cell transplantation and/or treatment with a proteasome inhibitor. The median time between prior therapy and trial enrollment was 9 months (range, 1-180 months). No grade 3-4 infusion-related reactions occurred. The most common grade ≥3 adverse events included respiratory infections (n = 4; 18%) and atrial fibrillation (n = 4, 18%). Hematologic complete and very-good-partial response occurred in 86% of patients. The median time to first and best hematologic response was 4 weeks and 3 months, respectively. Renal response occurred in 10 of 15 patients (67%) with renal involvement and cardiac response occurred in 7 of 14 patients (50%) with cardiac involvement. In summary, daratumumab is well tolerated in patients with relapsed AL amyloidosis and leads to rapid and deep hematologic responses and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT02841033.
Utility of serum free light chain ratio in response definition in patients with multiple myeloma
Authors: Abdallah Nadine , Kapoor Prashant , Murray David L. , Buadi Francis K. , Dingli David , Dispenzieri Angela , Gertz Morie A. , Go Ronald S. , Gonsalves Wilson I. , Hayman Suzanne R. , Kourelis Taxiarchis V. , Lacy Martha Q. , Leung Nelson , Lust John A. , Muchtar Eli , Warsame Rahma , Kyle Robert A. , Rajkumar S. Vincent , Kumar Shaji K.
Published: January 2020

Key Points

Patients with an abnormal sFLC ratio because of LC suppression have outcomes similar to those with a normal ratio. sFLC ratio has prognostic value in patients achieving CR who have an absence of clonal BMPCs assessed by MFC.
Comparative genomics of multidrug-resistant Enterococcus spp. isolated from wastewater treatment plants
Authors: Sanderson Haley , Ortega-Polo Rodrigo , Zaheer Rahat , Goji Noriko , Amoako Kingsley K. , Brown R. Stephen , Majury Anna , Liss Steven N. , McAllister Tim A.
Published: January 2020

Background

Wastewater treatment plants (WWTPs) are considered hotspots for the environmental dissemination of antimicrobial resistance (AMR) determinants. Vancomycin-Resistant Enterococcus (VRE) are candidates for gauging the degree of AMR bacteria in wastewater. Enterococcus faecalis and Enterococcus faecium are recognized indicators of fecal contamination in water. Comparative genomics of enterococci isolated from conventional activated sludge (CAS) and biological aerated filter (BAF) WWTPs was conducted.

Results

VRE isolates, including E. faecalis (n = 24), E. faecium (n = 11), E. casseliflavus (n = 2) and E. gallinarum (n = 2) were selected for sequencing based on WWTP source, species and AMR phenotype. The pangenomes of E. faecium and E. faecalis were both open. The genomic fraction related to the mobilome was positively correlated with genome size in E. faecium (p < 0.001) and E. faecalis (p < 0.001) and with the number of AMR genes in E. faecium (p = 0.005). Genes conferring vancomycin resistance, including vanA and vanM (E. faecium), vanG (E. faecalis), and vanC (E. casseliflavus/E. gallinarum), were detected in 20 genomes. The most prominent functional AMR genes were efflux pumps and transporters. A minimum of 16, 6, 5 and 3 virulence genes were detected in E. faecium, E. faecalis, E. casseliflavus and E. gallinarum, respectively. Virulence genes were more common in E. faecalis and E. faecium, than E. casseliflavus and E. gallinarum. A number of mobile genetic elements were shared among species. Functional CRISPR/Cas arrays were detected in 13 E. faecalis genomes, with all but one also containing a prophage. The lack of a functional CRISPR/Cas arrays was associated with multi-drug resistance in E. faecium. Phylogenetic analysis demonstrated differential clustering of isolates based on original source but not WWTP. Genes related to phage and CRISPR/Cas arrays could potentially serve as environmental biomarkers.

Conclusions

There was no discernible difference between enterococcal genomes from the CAS and BAF WWTPs. E. faecalis and E. faecium have smaller genomes and harbor more virulence, AMR, and mobile genetic elements than other Enterococcus spp.
Efficiency as a determinant of loyalty among users of a Community of Clinical Practice: a comparative study between the implementation and consolidation phases
Authors: Lacasta Tintorer David , Manresa Domínguez Josep Maria , Jiménez-Zarco Ana , Rodríguez-Blanco Teresa , Flayeh Beneyto Souhel , Torán-Monserrat Pere , Mundet Tuduri Xavier , Saigí-Rubió Francesc
Published: January 2020

Background

A community of clinical practice called the Online Communication Tool between Primary and Hospital Care (ECOPIH) was created to enable primary care and specialist care professionals to communicate with each other in order to resolve real clinical cases, thereby improving communication and coordination between care levels. The present work seeks to analyse whether ECOPIH makes it possible to reduce the number of referrals. To that end, the objectives are: (1) To find out the degree of loyalty among ECOPIH users, by comparing the medical professionals’ profiles in the tool’s implementation phase to those in its consolidation phase. (2) To evaluate the degree of fulfilment of users’ expectations, by establishing the determining factors that had an influence on the physicians’ intention to use ECOPIH in the implementation phase and observing whether its use had an effective, direct impact on the number of patient referrals that primary care physicians made to specialist care professionals.

Methods

Two studies were conducted. Based on a survey of all the physicians in a Primary Care area, Study 1 was a descriptive study in ECOPIH’s implementation phase. Study 2 was a randomised intervention study of ECOPIH users in the tool’s consolidation phase. The results from both studies were compared. Various bivariate and multivariate statistical techniques (exploratory factor analysis, cluster analysis, logistic regression analysis and ANOVA) were used in both studies, which were conducted on a sample of 111 and 178 physicians, respectively.

Results

We confirmed the existence of an ECOPIH user profile stable across both phases: under-50-year-old women. Regarding the second objective, there were two particular findings. First, the discriminant factors that had an influence on greater ECOPIH use were habitual Social media website and app use and Perceived usefulness for reducing costs. Second, PC professionals who were ECOPIH members made fewer referrals to SC professionals in Cardiology, Endocrinology and Gastroenterology than older PC professionals who were not ECOPIH members.

Conclusions

The use of a community of clinical practice by primary care and specialist care professionals helps to reduce the number of referrals among medical professionals.
Current status of integrating oncology and palliative care in Japan: a nationwide survey
Authors: Uneno Y. , Sato K. , Morita T. , Nishimura M. , Ito S. , Mori M. , Shimizu C. , Horie Y. , Hirakawa M. , Nakajima T. E. , Tsuneto S. , Muto M.
Published: January 2020

Background

Palliative care (PC) is increasingly recognized as essential for oncology care, and several academic societies strongly recommend integrating oncology and palliative care (IOP) in daily practice. Similarly, the Japanese government encouraged the implementation of IOP through the Cancer Control Act of 2007; however, its detailed progress remains unclear. Therefore, this cross-sectional nationwide survey was conducted to investigate the current status and hospital executive physicians’ perception of IOP.

Methods

The questionnaire was developed based on IOP indicators with international consensus. It was distributed to executive physicians at all government-designated cancer hospitals (DCHs, n = 399) and matched non-DCHs (n = 478) in November 2017 and the results were compared.

Results

In total, 269 (67.4%) DCHs and 259 (54.2%) non-DCHs responded. The number of PC resources in DCHs was significantly higher than those in non-DCHs (e.g., full-time PC physicians and nurses, 52.8% vs. 14.0%, p < 0.001; availability of outpatient PC service ≥3 days per week, 47.6% vs. 20.7%, p < 0.001). Routine symptom screening was more frequently performed in DCHs than in non-DCHs (65.1% vs. 34.7%, p < 0.001). Automatic trigger for PC referral availability was limited (e.g., referral using time trigger, 14.9% vs. 15.3%, p = 0.700). Education and research opportunities were seriously limited in both types of hospitals. Most executive physicians regarded IOP as beneficial for their patients (95.9% vs. 94.7%, p = 0.163) and were willing to facilitate an early referral to PC services (54.7% vs. 60.0%, p < 0.569); however, the majority faced challenges to increase the number of full-time PC staff, and < 30% were planning to increase the staff members.

Conclusions

This survey highlighted a considerable number of IOP indicators met, particularly in DCHs probably due to the government policy. Further efforts are needed to address the serious research/educational gaps.
The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial
Authors: Haidari Fatemeh , Banaei-Jahromi Nasrin , Zakerkish Mehrnoosh , Ahmadi Kambiz
Published: January 2020

Background

Polycystic Ovary Syndrome (PCOS) is known as the most common endocrine disorder of women in reproductive ages. With the increasing prevalence of PCOS in different countries, the use of herbal medicine as an alternative treatment is growing in these patients. This study aimed to evaluate the effects of flaxseed powder supplementation on metabolic biomarkers of patients with PCOS.

Methods

This randomized open-labeled controlled clinical trial was conducted on 41 patients with PCOS. The participants were randomized to take either flaxseed powder (30 g/day) plus lifestyle modification or only lifestyle modification for 12 weeks. Anthropometric and biochemical evaluations were performed for all patients at the beginning and end of the study.

Results

The flaxseed group showed a significant reduction in body weight, insulin concentration, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Triglycerides (TG), high-sensitivity C-Reactive Protein (hs-CRP), and leptin and an increase in Quantitative Insulin-Sensitivity Check Index (QUICKI), High Density Lipoprotein (HDL), and adiponectin compared to the baseline (p < 0.05). Flaxseed supplementation also led to a significant reduction in insulin concentration, HOMA-IR, TG, hs-CRP, Interleukin 6 (IL- 6), and leptin and an increase in QUICKI, HDL, and adiponectin compared to the control group (p < 0.05). No significant changes were observed in other parameters.

Conclusions

Flaxseed supplementation plus lifestyle modification was more effective compared to lifestyle modification alone in biochemical and anthropometric variables in patients with PCOS.

Trial registration

The trial protocol was approved by the Ethics Board at Ahvaz Jundishapur University of Medical Sciences and was registered at Iranian Registry of Clinical Trials (code:IRCT20120704010181N11).
Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy
Authors: Zhong Xiaoming , Zhang Hangtian , Zhu Ying , Liang Yuqing , Yuan Zhuolin , Li Jiachen , Li Jing , Li Xin , Jia Yifan , He Tian , Zhu Jiangyuan , Sun Yu , Jiang Wengting , Zhang Hui , Wang Cheng , Ke Zunfu
Published: January 2020

Cancer metastasis is the leading cause of cancer-related death. Circulating tumor cells (CTCs) are shed into the bloodstream from either primary or metastatic tumors during an intermediate stage of metastasis. In recent years, immunotherapy has also become an important focus of cancer research. Thus, to study the relationship between CTCs and immunotherapy is extremely necessary and valuable to improve the treatment of cancer. In this review, based on the advancements of CTC isolation technologies, we mainly discuss the clinical applications of CTCs in cancer immunotherapy and the related immune mechanisms of CTC formation. In order to fully understand CTC formation, sufficiently and completely understood molecular mechanism based on the different immune cells is critical. This understanding is a promising avenue for the development of effective immunotherapeutic strategies targeting CTCs.
Prognostic value and risk stratification of residual disease in patients with incidental gallbladder cancer
Authors: Ramos Emilio , Lluis Nuria , Llado Laura , Torras Jaume , Busquets Juli , Rafecas Antoni , Serrano Teresa , Mils Kristel , Leiva David , Fabregat Joan
Published: January 2020

Background and aim

Given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients.

Material and methods

A prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher’s exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis.

Results

RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041).

Conclusion

RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD.
Transvaginal ovarian drilling followed by controlled ovarian stimulation from the next day improves ovarian response for the poor responders with polycystic ovary syndrome during IVF treatment: a pilot study
Authors: Xu Bufang , Zhou Mingjuan , Cheng Meiyu , Zhang Dan , Wu Xian , Si Chenchen , Xia Lan , Xu Huihui , Li Jian , Chang Hsun-Ming , Leung Peter C. K. , Zhang Aijun
Published: January 2020

Background

Poor response patients with PCOS who are not susceptible to gonadotropin stimulation are more likely to have canceled cycles or poor clinical outcomes during IVF treatment. However, some limitations exist in the present therapies. In this study, we evaluated the effects of using the transvaginal ovarian drilling (TVOD) followed by controlled ovarian stimulation (COS) from the second day of these poor responders.

Methods

During IVF, 7 poor responders with PCOS and 28 PCOS patients (14 normal and 14 high responders) were recruited. All patients received COS with the gonadotropin-releasing hormone antagonist protocol. For the poor responders, after undergoing 10 to 14 days of ovulation induction with no response, the TVOD was applied and then ovarian stimulation was performed from the next day at the same gonadotropin dose. Serum samples during COS and follicular fluid samples from the dominant follicles on the oocyte pick-up (OPU) day in all three groups were collected. Besides, follicular fluid from small follicles (diameter < 1 cm) in the normal and high responders on the OPU day and those in the poor responders on the TVOD day were gathered. Hormonal levels were examined in all samples using immunometric assays.

Results

All the poor responders restored ovary response after receiving TVOD. There was no significant difference in the stimulation duration, total gonadotrophin dose used and the clinical outcomes among the three groups. The body mass index, serum and follicular levels of anti-Müllerian hormone (AMH) and testosterone in poor responders were higher than those in the other two groups, and the application of TVOD significantly decreased the levels of AMH and testosterone in both serum and follicular fluid.

Conclusions

TVOD followed by ovulation induction from the next day is effective and convenient for poor responders with PCOS. The decline of AMH and testosterone resulted from TVOD may be the main reason resulting in the recovery of ovary sensitivity to gonadotropins. The small sample size is the primary limitation of this study, future studies using a large population cohort and monitoring the long-term outcomes of this strategy will be required.

Trial registration

ChiCTR1900023612. Registered 04 June 2019-Retrospectively registered.
High-salt diet does not boost neuroinflammation and neurodegeneration in a model of α-synucleinopathy
Authors: Heras-Garvin Antonio , Refolo Violetta , Reindl Markus , Wenning Gregor K. , Stefanova Nadia
Published: January 2020

Aim

Pre-clinical studies in models of multiple sclerosis and other inflammatory disorders suggest that high-salt diet may induce activation of the immune system and potentiate inflammation. However, high-salt diet constitutes a common non-pharmacological intervention to treat autonomic problems in synucleinopathies such as Parkinson’s disease and multiple system atrophy. Since neuroinflammation plays an important pathogenic role in these neurodegenerative disorders, we asked here whether high-salt diet may aggravate the disease phenotype in a transgenic model of multiple system atrophy.

Methods

Nine-month-old PLP-hαSyn and matched wildtype mice received normal or high-salt diet for a period of 3 months. Behavioral, histological, and molecular analyses were performed to evaluate the effect of high-salt diet on motor decline, neuroinflammation, neurodegeneration, and α-synuclein accumulation in these mice.

Results

Brain subregion-specific molecular and histological analyses showed no deleterious effects of high-salt diet on the level of microglial activation. Moreover, neuroinflammation-related cytokines and chemokines, T cell recruitment or astrogliosis were unaffected by high-salt diet exposure. Behavioral testing showed no effect of diet on motor decline. High-salt diet was not related to the deterioration of neurodegeneration or α-synuclein accumulation in PLP-hαSyn mice.

Conclusions

Here, we demonstrate that high-salt diet does not aggravate neuroinflammation and neurodegeneration in PLP-hαSyn mice. Our findings discard a deleterious pro-neuroinflammatory effect of high-salt diet in multiple system atrophy.
Improved bioethanol productivity through gas flow rate-driven self-cycling fermentation
Authors: Wang Jie , Chae Michael , Bressler David C. , Sauvageau Dominic
Published: January 2020

Background

The growth of the cellulosic ethanol industry is currently impeded by high production costs. One possible solution is to improve the performance of fermentation itself, which has great potential to improve the economics of the entire production process. Here, we demonstrated significantly improved productivity through application of an advanced fermentation approach, named self-cycling fermentation (SCF), for cellulosic ethanol production.

Results

The flow rate of outlet gas from the fermenter was used as a real-time monitoring parameter to drive the cycling of the ethanol fermentation process. Then, long-term operation of SCF under anaerobic conditions was improved by the addition of ergosterol and fatty acids, which stabilized operation and reduced fermentation time. Finally, an automated SCF system was successfully operated for 21 cycles, with robust behavior and stable ethanol production. SCF maintained similar ethanol titers to batch operation while significantly reducing fermentation and down times. This led to significant improvements in ethanol volumetric productivity (the amount of ethanol produced by a cycle per working volume per cycle time)—ranging from 37.5 to 75.3%, depending on the cycle number, and in annual ethanol productivity (the amount of ethanol that can be produced each year at large scale)—reaching 75.8 ± 2.9%. Improved flocculation, with potential advantages for biomass removal and reduction in downstream costs, was also observed.

Conclusion

Our successful demonstration of SCF could help reduce production costs for the cellulosic ethanol industry through improved productivity and automated operation.
Temperature and pressure corrections applied to rock thermal conductivity: impact on subsurface temperature prognosis and heat-flow determination in geothermal exploration
Authors: Norden Ben , Förster Andrea , Förster Hans-Jürgen , Fuchs Sven
Published: January 2020

Precise knowledge of the subsurface thermal field plays a key role in the assessment of geothermal targets. Unfortunately, deep underground temperature data is generally scarce and a matter of research. To achieve first estimates for subsurface temperatures, steady-state conductive thermal modeling is commonly applied. Thereby the rock thermal conductivity is an essential parameter, which is usually determined under ambient laboratory conditions. To arrive with in situ thermal conductivity, the ambient values need to be corrected for in situ temperature and pressure. In this paper, we apply different conversion functions for the correction of thermal conductivity and study the impact on the resultant temperature and heat flow prognoses for a synthetic, upper crustal sedimentary and a magmatic scenario along 2-D geological cross sections. Application of the correction functions results in maximum temperature prognosis uncertainties of about 8 °C and 55 °C at 2 km depth and at 8 km depth, respectively. The effect positively correlates with the magnitude of the basal heat flow used in modeling. In contrast to the heat flow determined at depth, the resulting surface heat flow is only minor affected by the different correction functions applied. In addition, the modeled temperature at depth is strongly dependent on the type and sequence of application of the pressure and temperature correction equations.
Feasibility of Cancer Clinical Trial Enrollment Goals Based on Cancer Incidence
Authors: Tran George , Harker Matthew , Chiswell Karen , Unger Joseph M. , Fleury Mark E. , Hirsch Bradford , Miller Kimberly , d’Almada Philip , Tibbs Sheri , Zafar S. Yousuf
Published: January 2020

PURPOSE

More than 20% of US clinical trials fail to accrue sufficiently. Our purpose was to provide a benchmark for better understanding clinical trial enrollment feasibility and to assess relative levels of competition for patients by cancer diagnosis.

METHODS

The Database for Aggregate Analysis of ClinicalTrials.gov , up to date as of September 3, 2017, was used to identify actively recruiting, interventional oncology trials with US sites. Observational studies were excluded because not all are registered. Trials were categorized through Medical Subject Headings or free-text condition terms and sorted by cancer diagnosis. Trials that included more than one cancer diagnosis were included in the overall cohort but excluded when evaluating enrollment by cancer type. Trial enrollment slot availability was estimated between September 1, 2017, and August 31, 2018. Availability was estimated from total anticipated enrollment and duration, assuming a constant recruitment rate. Estimates for studies with both foreign and domestic sites were then prorated to calculate available enrollment in the United States alone. Ratios of the number of newly diagnosed patients in the United States available per trial slot were estimated using the American Cancer Society cancer incidence estimates for 2017.

RESULTS

A total of 4,598 interventional oncology trials were identified. Overall, the estimated ratio of newly diagnosed patients available per trial slot was 12.6. Estimated ratios of patients per trial slot for six cancer diagnoses with the highest potential of 12-month US enrollment were as follows: colorectal, 24.7; lung and bronchus, 20.1; prostate, 17.6; breast (female), 13.8; leukemia, 11.6; and brain and other nervous system, 6.0.

CONCLUSION

For all cancers, successfully accruing trials currently open would require that more than one in every 13 recently diagnosed patients (7.9%) enroll. This ratio and relative difficulty of accrual varies among cancers examined.
Relationship of Body Mass Index and Waist Circumference With Risk of New-Onset Proteinuria in Hypertensive Patients
Authors: Liu Mengyi , Zhang Zhuxian , Zhou Chun , He Panpan , Nie Jing , Liang Min , Liu Chengzhang , Xu Fanghua , Liao Guangzhou , Zhang Yan , Li Jianping , Wang Binyan , Wang Xiaobin , Huo Yong , Xu Xiping , Qin Xianhui
Published: January 2020

Context

The association of the combination of body mass index (BMI) and waist circumference (WC) with the risk of proteinuria has previously not been comprehensively investigated and results have been inconclusive.

Objective

To examine BMI and WC in relation to new-onset proteinuria in Chinese hypertensive patients.

Design and Setting

Post hoc analysis of the renal substudy of the China Stroke Primary Prevention Trial (CSPPT).

Patients

10 805 hypertensive patients without proteinuria at baseline.

Main Outcome Measure

The primary outcome was new-onset proteinuria, defined as a urine dipstick protein reading ≥ 1 + at the exit visit, after a median follow-up duration of 4.4 years.

Results

When analyzed separately, increased BMI (≥ 28 kg/m2, quartile 4; odds ratio [OR], 1.36; 95% confidence interval [CI], 1.08–1.72), or increased WC (≥ 91cm for females, quartile 4; OR, 1.35; 95% CI, 1.01–1.80; and ≥ 79 cm for males, quartile 2–4; OR, 1.60; 95% CI, 1.03–2.50) were each significantly associated with higher risk of new-onset proteinuria. When analyzed jointly, participants without increased BMI and increased WC had the lowest risk, while those with both increased BMI and increased WC had the highest risk of proteinuria (OR, 1.61; 95% CI, 1.21–2.13). Notably, participants with only increased WC also had significantly increased risk of proteinuria (OR, 1.39; 95% CI, 1.04–1.85).

Conclusion

In Chinese hypertensive patients, increased BMI and increased WC were individually and jointly associated with a higher risk of new-onset proteinuria, underscoring the value of monitoring both BMI and WC in assessing proteinuria risk.
Adding to the Denominator: A Case Report of Neuraxial Anesthesia for Cesarean Delivery in the Setting of Hemolysis, Elevated Liver Enzyme, Low Platelet, Thrombocytopenia, and Pulmonary Hypertension
Authors: Meng Marie-Louise , Bernstein Kyra , Hussey Patrick , Emeruwa Ukachi N. , Mourad Mirella , Haythe Jennifer , Landau Ruth
Published: January 2020

The acceptable platelet count for the safe provision of neuraxial anesthesia in obstetric patients is unknown. Comorbidities may sway a provider to perform neuraxial anesthesia, despite thrombocytopenia, as the putative risk of spinal–epidural hematoma may not outweigh the risks associated with general anesthesia. The case of a 22-year-old nulliparous woman undergoing a cesarean delivery with a new diagnosis of pulmonary hypertension and right heart failure, compounded with thrombocytopenia and possible Hemolysis, Elevated Liver Enzyme, and Low Platelet (HELLP) syndrome, is presented. Risks and benefits of general versus neuraxial anesthesia in this specific setting are reviewed.
More on the Missing Half Second
Authors: Makkar Jap-Nanak
Published: January 2020

This review essay compares two early and two recent texts by N. Katherine Hayles and Mark B. N. Hansen. Considering their recent work in the context of Ruth Leys’s critique of the turn to affect, I argue that Hayles and Hansen use neuroscientific conclusions on a “missing half second” to propose theories of technology’s impact. These critics neglect to provide explanations of a social or political kind, a trend that appears to be related to the lesser importance accorded to intention. I show the value of giving social explanations and of differentiating between humans and things in analyses.
Airpocalypse: Distributions of Life amidst Delhi’s Polluted Airs
Authors: Ghertner D. Asher
Published: January 2020

Extreme air pollution events have become a regular phenomenon in Delhi, triggering conjunctions of air pollution and death popularly referred to as airpocalypse. The city’s collective reckoning with bad air raises the question of how social justice is to be imagined when the source of death is diffuse and leaky. The Indian judiciary has taken up this question in earnest, dispersing the legal treatment of life away from its historical focus on individuated life-beings and toward a more atmospheric domain of biological abstractions and vital circulations: aggregate lung capacity, collective asthmatic risk, and distributed body parts. Life in law is now monitored through air quality indexes and climatological reports as much as X-rays or electrocardiograms, making it something not just shaped by the environment but itself an environmental condition. Following judicial discourse stemming from key pollution-related court cases, this article examines how these new distributions of life transform urban citizenship, which has been grounded in India in the right to life. It argues that multiple political potentialities unfold once citizenship is no longer anchored exclusively in the sovereign self, with emergent forms of atmospheric citizenship resting on a humanist principle of atmospheric sharing while simultaneously sustaining logics of atmospheric segregation.
The Work of Art in the Age of Digital Fragility
Authors: Rubio Fernando Domínguez , Wharton Glenn
Published: January 2020

Impermanence and fragility have become the defining conditions of the digital age. Technologies that were ubiquitous barely a decade ago, like floppy disks, now look like archaeological relics. It takes only a few years, if not months, before software environments are replaced by newer versions, often with limited backward compatibility. At the same time, digital technologies rely on hardware that has short life expectancy. The radical obsolescence of this new digital register raises a number of important questions. How are we going to prevent the fragile memories of contemporary digital cultures from receding into oblivion? This essay answers this question by looking at one of the institutions in which the problems associated with digital fragility are most especially felt, the Museum of Modern Art (MoMA), and by exploring the ontological displacements that digital objects are operating at the heart of the museum.
Pectin-Alginate Does Not Further Enhance Exogenous Carbohydrate Oxidation in Running
Authors: BARBER JAMES F. P. , THOMAS JOEL , NARANG BEN , HENGIST AARON , BETTS JAMES A. , WALLIS GARETH A. , GONZALEZ JAVIER T.
Published: January 2020

Purpose

Maximizing carbohydrate availability is important for many endurance events. Combining pectin and sodium alginate with ingested maltodextrin–fructose (MAL + FRU + PEC + ALG) has been suggested to enhance carbohydrate delivery via hydrogel formation, but the influence on exogenous carbohydrate oxidation remains unknown. The primary aim of this study was to assess the effects of MAL + FRU + PEC + ALG on exogenous carbohydrate oxidation during exercise compared with a maltodextrin–fructose mixture (MAL + FRU). MAL + FRU has been well established to increase exogenous carbohydrate oxidation during cycling compared with glucose-based carbohydrates (MAL + GLU). However, much evidence focuses on cycling, and direct evidence in running is lacking. Therefore, a secondary aim was to compare exogenous carbohydrate oxidation rates with MAL + FRU versus MAL + GLU during running.

Methods

Nine trained runners completed two trials (MAL + FRU and MAL + FRU + PEC + ALG) in a double-blind, randomized crossover design. A subset (n= 7) also completed a MAL + GLU trial to address the secondary aim, and a water trial to establish background expired13CO2enrichment. Participants ran at 60% V˙O2peak for 120 min while ingesting either water only or carbohydrate solutions at a rate of 1.5 g carbohydrate per minute.

Results

At the end of 120 min of exercise, exogenous carbohydrate oxidation rates were 0.9 (SD 0.5) g·min−1with MAL + GLU ingestion. MAL + FRU ingestion increased exogenous carbohydrate oxidation rates to 1.1 (SD 0.3) g·min−1(P= 0.038), with no further increase with MAL + FRU + PEC + ALG ingestion (1.1 (SD 0.3) g·min−1;P= 1.0). No time–treatment interaction effects were observed for plasma glucose, lactate, insulin, or nonesterified fatty acids, or for ratings of perceived exertion or gastrointestinal symptoms (all,P> 0.05).

Conclusion

To maximize exogenous carbohydrate oxidation during moderate-intensity running, athletes may benefit from consuming glucose(polymer)–fructose mixtures over glucose-based carbohydrates alone, but the addition of pectin and sodium alginate offers no further benefit.
Neck and Inspiratory Muscle Recruitment during Inspiratory Loading and Neck Flexion
Authors: DERBAKOVA ANASTASIA , KHUU STEVEN , HO KEVIN , LEWIS CHANTELLE , MA TIMOTHY , MELO LUANA T. , ZABJEK KARL F. , GOLIGHER EWAN C. , BROCHARD LAURENT , FREGONEZI GUILHERME , REID W. DARLENE
Published: January 2020

Purpose

This study aimed to compare muscle activation of the diaphragm (DIA), scalenes (SA), parasternal intercostals (PS), and sternomastoid (SM) during submaximal intermittent neck flexion (INF) versus submaximal inspiratory threshold loading (ITL) until task failure in healthy adults.

Methods

Twelve healthy adults performed submaximal ITL or INF tests in random order for 2 d. Surface electromyography was monitored to acquire root mean square (RMS) and median power frequency (MPF) from the SA, PS, SM, and DIA. Maximal inspiratory pressures and maximal voluntary contraction for neck flexion were determined. Next, participants performed the first submaximal test—ITL or INF—targeting 50% ± 5% of the maximal inspiratory pressure or maximal voluntary contraction, respectively, until task failure. After a rest, they performed the other test until task failure. Two days later, they performed ITL and INF but in the opposite order. The Borg scale assessed breathlessness and perceived exertion.

Results

Endurance times for ITL and INF were 38.1 and 26.3 min, respectively. INF activated three of four inspiratory muscles at higher average RMS (PS, SM, and SA) and at different MPF (PS, SM, and DIA but not SA) compared with ITL. During ITL, RMS did not change in the four inspiratory muscles over time, but MPF decreased in PS, SM, and SA (P < 0.04). In contrast, RMS increased in three of four inspiratory muscles (SM, PS, and SA) during INF, but MPF did not change throughout its duration. Borg rating was 3.9-fold greater than ITL compared with INF.

Conclusion

At a similar percentage of maximal load, INF evokes greater activation of primary muscles of inspiration (PS and SA) and a major accessory muscle of inspiration (SM) compared with ITL during a prolonged submaximal protocol.
High-Intensity Training and Saffron: Effects on Breast Cancer–related Gene Expression
Authors: NEZAMDOOST ZEYNAB , SAGHEBJOO MARZIYEH , HOSHYAR REYHANE , HEDAYATI MEHDI , KESKA ANNA
Published: January 2020

Purpose

Exercise training and some herbal components have an anticancer function and can suppress tumor growth. However, the role of these protective factors in altering breast cancer–related gene expression is still unknown. Thus, this study aimed to assess the effect of 4 wk of high-intensity interval training (HIIT) and saffron (Crocus sativus L.) aqueous extract (SAE) on Sirtuin-1 (SIRT1), human telomerase reverse transcriptase (hTERT), and p53 gene expression in female mice breast tumor tissue induced by 4T1 cell line.

Methods

This study was performed on female BALB/c mice. The 4T1 breast cancer cells were subcutaneously implanted, and mice were randomly sorted into the following groups: control, HIIT, SAE, HIIT + SAE (n = 10 mice per group), and sham (n = 4 mice per group). Mice were sacrificed at the end of the intervention period, and the expression of SIRT-1, hTERT, and p53 was determined by real-time polymerase chain reaction.

Results

The mRNA level of SIRT1 was increased in the HIIT + SAE group compared with the HIIT and control groups (P = 0.007 and P = 0.03, respectively). Moreover, the amount of mRNA of p53 was increased after a 4-wk HIIT compared with the control and HIIT + SAE groups in tumor tissue (P = 0.03 and P = 0.02, respectively). No change was found in the mRNA expression of hTERT between groups (P = 0.92).

Conclusions

These findings suggest that HIIT may reduce tumor burden through the upregulation of p53 associated with tumor suppression pathway. In contrast, the combination of HIIT and SAE did not alter p53 and SIRT1 expression levels and may suppress tumor growth by other mechanisms.
Activity Accumulation and Cardiometabolic Risk in Youth: A Latent Profile Approach
Authors: VERSWIJVEREN SIMONE J. J. M. , LAMB KAREN E. , LEECH REBECCA M. , SALMON JO , TIMPERIO ANNA , TELFORD ROHAN M. , MCNARRY MELITTA A. , MACKINTOSH KELLY A. , DALY ROBIN M. , DUNSTAN DAVID W. , HUME CLARE , CERIN ESTER , OLIVE LISA S. , RIDGERS NICOLA D.
Published: January 2020

Introduction

This cross-sectional study aimed to i) identify and characterize youth according to distinct physical activity (PA) and sedentary (SED) accumulation patterns, and ii) investigate associations of these derived patterns with cardiometabolic risk factors.

Methods

ActiGraph accelerometer data from 7- to 13-yr-olds from two studies were pooled (n = 1219; 843 (69%) with valid accelerometry included in analysis). Time accumulated in ≥5- and ≥10-min SED bouts, ≥1- and ≥5-min bouts of light, and ≥1-min bouts of moderate and vigorous PA was calculated. Frequency of breaks in SED was also obtained. Latent profile analysis was used to identify groups of participants based on their distinct accumulation patterns. Linear and logistic regression models were used to test associations of group accumulation patterns with cardiometabolic risk factors, including adiposity indicators, blood pressure, and lipids. Total PA and SED time were also compared between groups.

Results

Three distinct groups were identified: “prolonged sitters” had the most time in sustained SED bouts and the least time in vigorous PA bouts; “breakers” had the highest frequency of SED breaks and lowest engagement in sustained bouts across most PA intensities; and “prolonged movers” had the least time accumulated in SED bouts and the most in PA bouts across most intensities. Although breakers engaged in less time in PA bouts compared with other groups, they had the healthiest adiposity indicators. No associations with the remaining cardiometabolic risk factors were found.

Conclusion

Youth accumulate their daily activity in three distinct patterns (prolonged sitters, breakers, and prolonger movers), with those breaking up sitting and least time in prolonged PA bouts across the day having a lower adiposity risk. No relationships with other cardiometabolic risk factors were identified.