bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards a liquid healthcare: primary care organisational and management strategies during the COVID-19 pandemic - a qualitative study
Authors: Pulido-Fuentes Montserrat , González Luisa Abad , Reneo Isaac Aranda , Cipriano-Crespo Carmen , Flores-Martos Juan Antonio , Santos Ana Palmar
Published: May 2022

Background

The COVID-19 pandemic has changed the organisational and management strategies of healthcare institutions such as primary care centres. Organisational culture as well as leadership style are key issues for the success of these institutions. Due to the multidimensional nature of identity processes, it is necessary to explore the changes experienced by health professionals from these perspectives. This study explores health professionals’ organisational and management strategies in primary care settings during the COVID-19 pandemic.

Design

Qualitative, exploratory study based on the analysis of participants’ accounts within a hermeneutic phenomenologicaly approach.

Methods

Research was conducted in primary care settings in two neighbouring Spanish healthcare regions. The sample included participants with different demographics (gender, age), professional roles (practice managers, general practitioners, paediatricians), employment status (permanent, temporary, zero-hours), and years of experience (under or over ten years’ experience). Data were collected between July and December 2020 through focus groups and in-depth, semi-structured individual interviews.

Results

A total of 53 primary care workers participated in the study, of which 38 were individually interviewed and 15 participated in three focus groups. Of these, 78.4% were healthcare professionals, 49% were female nurses, and 70.5% had more than 10 years of work experience in primary care. Two main themes emerged: “liquid” healthcare and “the best healthcare system in the world”. During the first wave of the COVID-19 pandemic, new, more fluid organisational and management models were implemented in primary care settings, which have remained in place since. Primary care workers’ perceived a lack of appreciation and inclusion in decision-making that risked their alienation and disengagement.

Conclusion

Primary care workers’ professional identity became gradually blurred due to shifting perceptions of their professional roles in a context of increasing improvisation and flexible working practices. This affected their professional performance.

Trial Registration

The study was approved by the Clinical Research Ethical Committee of the Talavera de la Reina Integrated Management Area (CEIm del AGI de Talavera de la Reina in Spain, Hospital Nuestra Señora del Prado, ref: 23/2020).
Effect of hospital attributes on patient preference among outpatient attendants in Wolaita Zone, Southern Ethiopia: discrete choice experiment study
Authors: Lendado Tigabu Addisu , Bitew Shimelash , Elias Fikadu , Samuel Serawit , Assele Desalegn Dawit , Asefa Merid
Published: May 2022

Background

Patient preference has preceded the use of health care services, and it has been affected by different hospital attributes. Meanwhile, the number of patients receiving vital health intervention is particularly low in Ethiopia. Therefore, this study aimed to determine the effect of hospital attributes on patient preference for outpatients in the Wolaita area in September 2020.

Methods

A discrete choice experimental study was applied to determine the effect of hospital attributes on patient preference with a sample size of 1077. The experimental survey was conducted among outpatient attendants selected through a systematic random sampling approach. Six key attributes (competence of healthcare providers; availability of medical equipment and supplies; cost of service; wait time; distance; and hospital reputation) deduced from various hospital attributes were used to elicit the patient preferences. The data was collected from participants through the Open Data Kit application. A random effect probit model with marginal willingness to pay measure and partially log-likelihood analysis was applied to extract important attributes. We used STATA version 15 software for analysis, and the fitness of the model was verified by the calculated p-value for the Wald chi-square with a cut-point value of 0.05.

Result

One thousand forty-five patients who received outpatient care participated in the study. The random effect probit results have shown that all hospital attributes included in the study were significantly valued by patients while choosing the hospital (p-value < 0.001). Meanwhile, based on marginal willingness to pay and partial log-likelihood analysis, the competence of health care providers was identified as the most important attribute followed by the availability of medical equipment and supplies in hospitals.

Conclusion and recommendation

The results suggested that the quality of health care providers and availability of medical equipment and supply in hospitals would be primary interventional points for improving the patient preference of hospitals. Assessment, education, and training are recommended for enhancing the quality of health care providers. And stock balance checks, inspections, and accreditation are believed to be valuable for improving the availability of equipment and supply in hospitals.
Influences of post-implementation factors on the sustainability, sustainment, and intra-organizational spread of complex interventions
Authors: Song Yuting , MacEachern Lauren , Doupe Malcolm B. , Ginsburg Liane , Chamberlain Stephanie A. , Cranley Lisa , Easterbrook Adam , Hoben Matthias , Knopp-Sihota Jennifer , Reid R. Colin , Wagg Adrian , Estabrooks Carole A. , Keefe Janice M. , Rappon Tim , Berta Whitney B.
Published: May 2022

Background

Complex interventions are increasingly applied to healthcare problems. Understanding of post-implementation sustainment, sustainability, and spread of interventions is limited. We examine these phenomena for a complex quality improvement initiative led by care aides in 7 care homes (long-term care homes) in Manitoba, Canada. We report on factors influencing these phenomena two years after implementation.

Methods

Data were collected in 2019 via small group interviews with unit- and care home-level managers (n = 11) from 6 of the 7 homes using the intervention. Interview participants discussed post-implementation factors that influenced continuing or abandoning core intervention elements (processes, behaviors) and key intervention benefits (outcomes, impact). Interviews were audio-recorded, transcribed verbatim, and analyzed with thematic analysis.

Results

Sustainment of core elements and sustainability of key benefits were observed in 5 of the 6 participating care homes. Intra-unit intervention spread occurred in 3 of 6 homes. Factors influencing sustainment, sustainability, and spread related to intervention teams, unit and care home, and the long-term care system.

Conclusions

Our findings contribute understanding on the importance of micro-, meso-, and macro-level factors to sustainability of key benefits and sustainment of some core processes. Inter-unit spread relates exclusively to meso-level factors of observability and practice change institutionalization. Interventions should be developed with post-implementation sustainability in mind and measures taken to protect against influences such as workforce instability and competing internal and external demands. Design should anticipate need to adapt interventions to strengthen post-implementation traction.
Factors associated with deficiencies in packaging of surgical instrument by staff at a single center in China
Authors: Chen Yanhua , Yi Liangying , Hu Juan , Hu Ruixue
Published: May 2022

Background

Surgical instrument packaging quality directly affects the safety and performance of surgery. We aimed to investigate the factors causing defects in surgical instrument packaging and recommend strategies to prevent defects in surgical instrument packaging.

Methods

We collected surgical instrument packaging data regarding age, gender, length of service, educational background, number of staff dealing with packaging, time period of packaging, instrument specification, where the wrap was intact, whether the wrap reached the required quality of cleaning, and whether the instruments were satisfactorily cleaned in compliance with guidelines from 5000 surgical instrument packages during June-December 2018 at Central Sterile Supply Department of the West China Second University Hospital, Sichuan University. Meanwhile, a questionnaire survey completed by the operating room staff using surgical instruments was used to measure the level of their satisfaction with the instruments in the packages. We utilized single-factor analysis to investigate possible factors that might cause defects in surgical instrument packaging, and conducted multivariate logistic regression analysis of the factors associated with defects in packaging.

Results

Length of service, educational background, number of staff dealing with packaging, time period of packaging, instrument structure, whether the wrap was intact, whether the wrap reached the required quality of cleaning, and whether the surgical instruments were satisfactorily cleaned in compliance with guidelines were the factors significantly (P < 0.05) associated with defects in surgical instrument packaging.

Conclusion

This study reveals that various factors are associated with defects in surgical instrument packaging. Recommendations for reducing incidences of defects include improved scheduling of packaging workload, greater provision of training in packaging skills, and standardization of packaging procedure.
Improving care for immigrant women before, during, and after childbirth – what can we learn from regional interventions within a national program in Sweden?
Authors: Nyström M. E. , Larsson E. C. , Pukk Härenstam K. , Tolf S.
Published: May 2022

Background

Migration has increased the number of immigrant women in western countries, which has led to a need to adapt sexual and reproductive health (SRH) care to a larger variety of experiences. Examples of problems are poor access/utilization of SRH services among migrants and a comparatively higher rate of mortality and morbidity in relation to pregnancy, especially among those from low- and middle-income settings. Attempts to improve SHR care must consider the complexity of both the problem and the system. A national program to improve women’s health in Sweden provided opportunities to study interventions aimed at immigrant women, using a complexity theory lens. The purpose was to explore the characteristics and complexity of regional interventions aiming to improve care and health of immigrant women before, during and after childbirth, and provide knowledge on how regional healthcare actors perceive and address problems in these areas.

Methods

This archival research study is based on qualitative data from detailed yearly reports of all regional program interventions (n = 21 regions) performed between January 2017 and January 2019. The archival data consists of the regional actors’ answers to an extensive questionnaire-like template, where the same questions were to be filled in for each reported intervention. Data analyses were performed in several steps, combining classic and directive content analysis.

Results

Six problem categories were addressed by 54 regional interventions, 26 directed at immigrant women and their families, 11 at healthcare staff, and 17 at the organizational system. The simple level interventions (n = 23) were more unilateral and contained information campaigns, information material and translation, education, mapping e.g., of genital mutilation, and providing staff and/or financial resources. The complicated interventions (n = 10) concerned increasing communication diversity e.g., by adding iPads and out-reach visits. The complex interventions (n = 21), e.g., health schools, integration of care, contained development, adaptions, and flexibility with regards to the immigrant women’s situation, and more interaction among a diversity of actors, also from the wider welfare system.

Conclusions

It is important that complex problems, such as ensuring equal care and health among a diverse population, are addressed with a mix of simple, complicated, and complex interventions. To enhance intended change, we suggest that pre-requisites e.g., communication channels and knowledge on behalf of immigrant women and staff, are ensured before the launch of complex interventions. Alternatively, that simple level interventions are embedded in complex interventions.
Ocular complications with the use of radium-223: a case series
Authors: Bloom Julie R. , Castillejos Alexandra G. , Jones Brianna , Patel Nimesh , Rosenstein Barry S. , Stock Richard G.
Published: May 2022

Background

Radium-223 is used for the treatment of osseous metastases in castrate-resistant prostate cancer, and has been shown to increase time to the first skeletal-related event, reduce the rate of hospitalization, and improve quality of life. It is well tolerated, with hematologic toxicity as the main adverse event. Thus far, no ocular complication has been reported in the literature after initial administration of radium-223 with a single case reported of ocular complications after a patient’s second course of radium-223.

Case presentations

We present three cases of ocular complications after the use of radium-223 in patients with metastatic prostatic adenocarcinoma. Ocular complications presented as blurry vision, and formal diagnosis included uveitis and hyphema.

Conclusions

Documentation of adverse events is exceedingly important due to the high incidence of metastatic prostate cancer and increasing interest for the use of radium-223 in other osteoblastic disease. The authors postulate that these ocular complications may be a result of radiation’s potential effect on neovascularization, polypharmacy, or the biomolecular effects of radium-223 on integral signaling proteins, potentially coupled with poor underlying ocular health.
Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis
Authors: Qi Wenchuan , Li Xiang , Ren Yanrong , Liu Xueying , Fu Hongjuan , Wang Xiao , Li Xiao , Xiong Jian , Zheng Qianhua , Cai Dingjun , Liang Fanrong
Published: May 2022

Background

Myocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients’ lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a variety of regulatory functions in myocardial fibrosis, but whether electroacupuncture can inhibit myocardial fibrosis by regulating lncRNA has rarely been reported.

Methods

In this study, we constructed myocardial fibrosis rat models using isoproterenol (ISO) and treated rats with electroacupuncture at PC6 point and non-point as control. Hematoxylin–eosin, Masson and Sirius Red staining were performed to assess the pathological changes and collagen deposition. The expression of fibrosis-related markers in rat myocardial tissue were detected by RT-qPCR and Western blot. Miat, an important long non-coding RNA, was selected to study the regulation of myocardial fibrosis by electroacupuncture at the transcriptional and post-transcriptional levels. In post-transcriptional level, we explored the myocardial fibrosis regulation effect of Miat on the sponge effect of miR-133a-3p. At the transcriptional level, we studied the formation of heterodimer PPARG–RXRA complex and promotion of the TGF-β1 transcription.

Results

Miat was overexpressed by ISO injection in rats. We found that Miat can play a dual regulatory role in myocardial fibrosis. Miat can sponge miR-133a-3p in an Ago2-dependent manner, reduce the binding of miR-133a-3p target to the 3ʹUTR region of CTGF mRNA and improve the protein expression level of CTGF. In addition, it can also directly bind with PPARG protein, inhibit the formation of heterodimer PPARG–RXRA complex and then promote the transcription of TGF-β1. Electroacupuncture at PC6 point, but not at non-points, can reduce the expression of Miat, thus inhibiting the expression of CTGF and TGF-β1 and inhibiting myocardial fibrosis.

Conclusion

We revealed that electroacupuncture at PC6 point can inhibit the process of myocardial fibrosis by reducing the expression of lncRNA Miat, which is a potential therapeutic method for myocardial fibrosis.
Developing an artificial intelligence method for screening hepatotoxic compounds in traditional Chinese medicine and Western medicine combination
Authors: Chen Zhao , Zhao Mengzhu , You Liangzhen , Zheng Rui , Jiang Yin , Zhang Xiaoyu , Qiu Ruijin , Sun Yang , Pan Haie , He Tianmai , Wei Xuxu , Chen Zhineng , Zhao Chen , Shang Hongcai
Published: May 2022

Backgrounds

Traditional Chinese medicine and Western medicine combination (TCM-WMC) increased the complexity of compounds ingested.

Objective

To develop a method for screening hepatotoxic compounds in TCM-WMC based on chemical structures using artificial intelligence (AI) methods.

Methods

Drug-induced liver injury (DILI) data was collected from the public databases and published literatures. The total dataset formed by DILI data was randomly divided into training set and test set at a ratio of 3:1 approximately. Machine learning models of SGD (Stochastic Gradient Descent), kNN (k-Nearest Neighbor), SVM (Support Vector Machine), NB (Naive Bayes), DT (Decision Tree), RF (Random Forest), ANN (Artificial Neural Network), AdaBoost, LR (Logistic Regression) and one deep learning model (deep belief network, DBN) were adopted to construct models for screening hepatotoxic compounds.

Result

Dataset of 2035 hepatotoxic compounds was collected in this research, in which 1505 compounds were as training set and 530 compounds were as test set. Results showed that RF obtained 0.838 of classification accuracy (CA), 0.827 of F1-score, 0.832 of Precision, 0.838 of Recall, 0.814 of area under the curve (AUC) on the training set and 0.767 of CA, 0.731 of F1, 0.739 of Precision, 0.767 of Recall, 0.739 of AUC on the test set, which was better than other eight machine learning methods. The DBN obtained 82.2% accuracy on the test set, which was higher than any other machine learning models on the test set.

Conclusion

The DILI AI models were expected to effectively screen hepatotoxic compounds in TCM-WMC.
UPRmt activation improves pathological alterations in cellular models of mitochondrial diseases
Authors: Suárez-Rivero Juan M. , Pastor-Maldonado Carmen J. , Povea-Cabello Suleva , Álvarez-Córdoba Mónica , Villalón-García Irene , Talaverón-Rey Marta , Suárez-Carrillo Alejandra , Munuera-Cabeza Manuel , Reche-López Diana , Cilleros-Holgado Paula , Piñero-Perez Rocío , Sánchez-Alcázar José A.
Published: May 2022

Background

Mitochondrial diseases represent one of the most common groups of genetic diseases. With a prevalence greater than 1 in 5000 adults, such diseases still lack effective treatment. Current therapies are purely palliative and, in most cases, insufficient. Novel approaches to compensate and, if possible, revert mitochondrial dysfunction must be developed.

Results

In this study, we tackled the issue using as a model fibroblasts from a patient bearing a mutation in the GFM1 gene, which is involved in mitochondrial protein synthesis. Mutant GFM1 fibroblasts could not survive in galactose restrictive medium for more than 3 days, making them the perfect screening platform to test several compounds. Tetracycline enabled mutant GFM1 fibroblasts survival under nutritional stress. Here we demonstrate that tetracycline upregulates the mitochondrial Unfolded Protein Response (UPRmt), a compensatory pathway regulating mitochondrial proteostasis. We additionally report that activation of UPRmt improves mutant GFM1 cellular bioenergetics and partially restores mitochondrial protein expression.

Conclusions

Overall, we provide compelling evidence to propose the activation of intrinsic cellular compensatory mechanisms as promising therapeutic strategy for mitochondrial diseases.
The influence of maturation, fitness, and hormonal indices on minutes played in elite youth soccer players: a cross-sectional study
Authors: Eskandarifard Ebrahim , Nobari Hadi , Clemente Filipe Manuel , Silva Rui , Clark Cain C. T. , Sarmento Hugo , Figueiredo António José
Published: May 2022

Background

The main purpose of this study was to investigate the relationships between minutes played (MP) with maturity status, fitness, and hormonal levels, and to quantify their influence on minutes played.

Methods

Twenty-four elite youth soccer players under-16 years participated in this study, over a full-season period. Anthropometric measures, maturity status, hormonal and physical fitness levels were collected. Participants were monitored during the season. After the end-season, players were assessed in 6 different tests over a four-day period.

Results

The maximum oxygen consumption (V̇O2max) was strongly correlated with MP (r = 0.75), maturity offset (r = 0.52), and countermovement jump (r = 0.53). Multiple linear regression explained 76% of MP (F (8, 15) = 6.05, p = 0.001), with an R2 of 0.76. Moreover, Growth hormone (GH) and V̇O2max. were the most influential factors in MP (F (2, 21) = 17.92, p ≤ 0.001), with an R2 of 0.63.

Conclusion

High levels of GH and V̇O2max have a preponderant role in MP by elite youth soccer players, it appears to be more pragmatic to consider other contextual dimensions, as they can impact selection for competition and minutes of participation in a match.
Accuracy, inter- and intrarater reliability, and user-experience of high tibial osteotomy angle measurements for preoperative planning: manual planning PACS versus semi-automatic software programs
Authors: Laven Iris E. W. G. , Schröder Femke F. , de Graaff Feike , Rompen J. Christiaan , Hoogeslag Roy A. G. , van Houten Albert H.
Published: May 2022

Purpose

To compare the accuracy, inter- and intrarater reliability, and user-experience of manual and semi-automatic preoperative leg-alignment measurement planning software for high tibial osteotomy (HTO).

Methods

Thirty patients (31 lower limbs) who underwent a medial opening wedge HTO between 2017 and 2019 were retrospectively included. The mechanical lateral distal femur angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and planned correction angle were measured on preoperative long-leg full weight-bearing radiographs utilising PACS Jivex Review® v5.2 manual and TraumaCad® v2.4 semi-automatic planning software. Independent measurements were performed by four raters. Two raters repeated the measurements. Accuracy in the standard error of measurement (SEM), inter- and intrarater reliability, and user-experience were analysed. Additionally, measurements errors of more than 3° were remeasured and reanalysed.

Results

The SEMs of all measured varus malalignment angles and planned correction angle were within 0.8° of accuracy for both software programs. Measurements utilising the manual software demonstrated moderate interrater intraclass correlation coefficient (ICC)-values for the mLDFA and mMPTA, and an excellent interrater ICC-value for the correction angle (0.810, 0.779, and 0.981, respectively). Measurements utilising the semi-automatic software indicated excellent interrater ICC-values for the mLDFA, mMPTA, and correction angle (0.980, 0.909, and 0.989, respectively). The intrarater reliability varied substantially per angle, presenting excellent intrarater agreements by both raters (ICC >  0.900) for the correction angle in each software program as well as poor-to-excellent ICC-values for the mLDFA (0.282–0.951 and 0.316–0.926) and mMPTA (0.893–0.934 and 0.594–0.941) in both the manual planning and semi-automatic software. Regarding user-experience, semi-automatic software was preferred by two raters, while the other two raters had no distinctive preference. After remeasurement of five outliers, excellent interrater ICC-values were found for the mLDFA (0.913) and mMPTA (0.957).

Conclusions

Semi-automatic software outperforms the manual software when user-experience and outliers are considered. However, both software programs provide similar performance after remeasurement of the human-related erroneous outliers. For clinical practice, both programs can be utilised for HTO planning.

Level of evidence

Diagnostic study, Level III.
Predicting cash holdings using supervised machine learning algorithms
Authors: Özlem Şirin , Tan Omer Faruk
Published: May 2022

This study predicts the cash holdings policy of Turkish firms, given the 20 selected features with machine learning algorithm methods. 211 listed firms in the Borsa Istanbul are analyzed over the period between 2006 and 2019. Multiple linear regression (MLR), k-nearest neighbors (KNN), support vector regression (SVR), decision trees (DT), extreme gradient boosting algorithm (XGBoost) and multi-layer neural networks (MLNN) are used for prediction. Results reveal that MLR, KNN, and SVR provide high root mean square error (RMSE) and low R2values. Meanwhile, more complex algorithms, such as DT and especially XGBoost, derive higher accuracy with a 0.73 R2value. Therefore, using advanced machine learning algorithms, we may predict cash holdings considerably.
Out-of-the-classroom learning of English vocabulary by EFL learners: investigating the effectiveness of mobile assisted learning with digital flashcards
Authors: Zakian Maryam , Xodabande Ismail , Valizadeh Mohammadreza , Yousefvand Mohammad
Published: May 2022

The importance of vocabulary knowledge as one of the most challenging aspects of foreign language learning has been widely acknowledged. In order to facilitate learning vocabulary items in English by language learners, mobile assisted vocabulary learning attracted considerable attention in recent years. Nevertheless, the application of mobile devices for learning the most frequently used vocabulary items in core vocabulary lists received far less attention. To address this gap, the current study investigated the contribution of a digital flashcard application (i.e. NGSL builder) designed for smartphone devices in out-of-the-classroom learning of essential vocabulary in English among EFL learners. The participants were 86 university students in experimental and control groups. In addition to formal language education during a semester, the experimental group used the mobile application for studying vocabulary items outside the classroom, while the control group used traditional materials (i.e. word list) to study the same content. The participants’ vocabulary knowledge was measured in three times (pre, post, and delayed posttest), and the results revealed that the use of mobile applications contributed significantly to vocabulary knowledge development, and those in the experimental group outperformed their counterparts in the control group. The findings also provided empirical evidence for the long-term impacts of mobile-assisted vocabulary learning. The study highlights the significance of mobile technologies in helping L2 learners to acquire essential vocabulary in English and discusses the pedagogical implications of these findings.
Exploring Student Perspectives: How Graduate Students in a Life Science Department Define Success
Authors: Weatherton Maryrose , Schussler Elisabeth E.
Published: May 2022

This study explores how 10 life science graduate students define success and how they describe their experiences related to success. Results indicate that students have multiple, diverse components within their definitions of success. Connections between students’ definitions and their sense of belonging, well-being, and persistence are discussed.
Heterogeneous characteristics and controlling factors of oil bearing of the Chang 7 shale in the Ordos Basin
Authors: Li Peng , Liu Zhongbao , Bi He , Fan Jingjing , Zhang Rui , Huang Zhenkai , Bian Ruikang , Wang Pengwei
Published: May 2022

Oil-bearing evaluation is the key issue of shale oil geologic exploration, which affects the mobility and effective development of the remaining oil in the shale system. To study the oil content and its controlling factors of shale in Chang 7 member of the Yanchang Formation in the Ordos Basin, we take the core of well H317 as the main research object, analyze the oil-bearing characteristics of shale by conventional rock pyrolysis and multistep pyrolysis experimental methods, and analyze the change characteristics of the elements by handheld X-ray fluorescence. The results indicate that the organic heterogeneity of Chang 7 shale in well H317 is obvious. It can be divided into upper shale and lower shale with 2467 m as the boundary. The upper shale has low total organic carbon (TOC), poor kerogen type, and slightly low oil content, but strong mobility. The lower shale has high TOC, good kerogen type, and good oil content, but poor mobility. The content and type of organic carbon in shale have obvious control effect on oil bearing and mobility. Differences in paleosedimentary environment control the formation of original sedimentary organic matter. During the lower shale deposition period, the climate was humid and the terrigenous input was relatively weak, high paleoproductivity and strong reducing water effectively preserved the original sedimentary organic matter, and finally formed an organic-rich interval with high TOC. Early diagenesis further altered the abundance and type of original organic matter.
A Window of Opportunity to Overcome Therapeutic Failure in Neuro-Oncology
Authors: Vogelbaum Michael A. , Li Gongbo , Heimberger Amy B. , Lang Frederick F. , Fueyo Juan , Gomez-Manzano Candelaria , Sanai Nader
Published: May 2022

Glioblastoma is the most common primary malignant brain neoplasm and it remains one of the most difficult-to-treat human cancers despite decades of discovery and translational and clinical research. Many advances have been made in our understanding of the genetics and epigenetics of gliomas in general; yet, there remains an urgent need to develop novel agents that will improve the survival of patients with this deadly disease. What sets glioblastoma apart from all other cancers is that it develops and spreads within an organ that renders tumor cells inaccessible to most systemically administered agents because of the presence of the blood-brain barrier. Inadequate drug penetration into the central nervous system is often cited as the most common cause of trial failure in neuro-oncology, and even so-called brain-penetrant therapeutics may not reach biologically relevant concentrations in tumor cells. Evaluation of the pharmacokinetics and pharmacodynamics of a novel therapy is a cornerstone of drug development, but few trials for glioma therapeutics have incorporated these basic elements in an organ-specific manner. Window-of-opportunity clinical trial designs can provide early insight into the biological plausibility of a novel therapeutic strategy in the clinical setting. A variety of window-of-opportunity trial designs, which take into account the limited access to treated tissue and the challenges with obtaining pretreatment control tissues, have been used for the initial development of traditional and targeted small-molecule drugs and biologic therapies, including immunotherapies and oncolytic viral therapies. Early-stage development of glioma therapeutics should include a window-of-opportunity component whenever feasible.
Building Modern Cancer Care Services in Sub-Saharan Africa Based on a Clinical-Research Care Model
Authors: Orem Jackson
Published: May 2022

Cancer is as old as humankind; there are examples of cancer treatment in ancient Egyptian civilizations. Globally, there has been rapid evolution of oncologic practices over many decades using different modalities, their complexities notwithstanding. These developments have resulted in visible improvements in outcomes for a complex medical condition.
Patient Experience in Clinical Trials: Quality of Life, Financial Burden, and Perception of Care in Patients With Multiple Myeloma or Lymphoma Enrolled on Clinical Trials Compared With Standard Care
Authors: Sidana Surbhi , Allmer Cristine , Larson Melissa C. , Dueck Amylou , Yost Kathleen , Warsame Rahma , Thanarajasingam Gita , Cerhan James R. , Paludo Jonas , Rajkumar S. Vincent , Habermann Thomas M. , Nowakowski Grzegorz S. , Lin Yi , Gertz Morie A. , Witzig Thomas , Dispenzieri Angela , Gonsalves Wilson I. , Ansell Stephen M. , Thompson Carrie A. , Kumar Shaji K.
Published: May 2022

PURPOSE:

Patients' concerns regarding clinical trial (CT) participation include apprehension about side effects, quality of life (QoL), financial burden, and quality of care.

METHODS:

We prospectively evaluated the experience of patients with multiple myeloma or lymphoma who were treated on CTs (CT group, n = 35) versus patients treated with standard approaches (non-CT group, n = 88) focusing on QoL, financial burden of care, and patients' perception of quality of care over a 1-year period.

RESULTS:

There were no significant differences in any of the patient-reported outcomes in CT versus non-CT groups. We observed an initial decline in overall QoL in the first 3 months across both groups, driven primarily by physical and functional well-being. QoL gradually improved and was above baseline by month 12. Patients reported highest improvement in the functional well-being subdomain. Patients in both groups reported high satisfaction with the quality of care received, and there were no differences in overall satisfaction, communication with team, or access to care. At baseline, 16%-19% of patients reported financial burden, which increased to a peak of 33% in the CT group and to 49% in the non-CT group over the course of 1 year. There was no significant difference in financial burden in the two groups overall. Most of the patients reported getting all the care that was deemed medically necessary in both groups. However, a significant proportion of patients reported having to make other kinds of financial sacrifices because of their cancer (CT group: 33% of patients at baseline and 21%-40% over 1 year; non-CT group: 19% at baseline and 25%-36% over 1 year).

CONCLUSION:

Patients treated on CTs reported comparable QoL and quality of care with the non-CT group. A high proportion of patients reported financial burden over time in both groups. Our findings can serve as a guide to educate patients regarding CT participation and highlight the need to address the significant financial burden experienced by patients with cancer.
Effects of Conformation on Doping Efficiency in π-Extended Bipyranylidene Molecules: Relationship between Molecular Structure and Electron-Doping Ability for Developing n-Type Organic Thermoelectrics
Authors: Matsuo Takaya , Kawabata Kohsuke , Takimiya Kazuo
Published: May 2022

Electron doping is an essential process for developing n-type organic thermoelectric materials, and thus the search for efficient n-type dopants is critically important. By replacing the central 1-methylpyrrole ring in 2,5-bis((2,6-diphenyl-4H-pyran-4-ylidene)methyl)-1-methylpyrrole (1) with electron-rich 3,4-ethylenedioxythiophene and 2,2′-bis(3,4-ethylenedioxythiophene) moieties, we synthesized new candidate molecules (2 and 3, respectively) as n-type dopants. The single-crystal X-ray analyses of 1 and 3 elucidated that 3 has a totally planar π-conjugated structure over the whole molecule, whereas 1 has a non-planar structure. Although the energy levels of the highest occupied molecular orbitals of 1–3 evaluated by the electrochemical measurement in solution were not significantly different, the work function of 3 thin film evaluated by the Kelvin probe method was slightly higher than those of 1 and 2. Furthermore, 3 was capable of electron-doping to an n-type semiconducting polymer, poly(benzimidazobenzophenanthroline) (BBL), and the resulting doped BBL showed decent thermoelectric characteristics with the power factor of 1.25 × 10−3 µW m−1 K−2, which was higher by one order of magnitude than those of 1- and 2-doped BBL thin films. These results imply that the high planarity of 3 can contribute to electron-doping ability, which could be useful information for further development of n-type dopants for organic thermoelectric applications.
Calibration of K and alpha (α) for bulk commodities
Authors: Minnitt R. , Mukhopadhyay D. , Lautze L.
Published: May 2022

In order to minimise the sampling error and sampling bias associated with the sampling of metal bearing ores it is essential that the heterogeneity characteristics of the ores be fully appreciated. Heterogeneity tests were carried out on the significantly different manganiferous ores produced at Wessels and Mamatwan mines near Hotazel, South Africa, for the purpose of establishing an optimal sampling protocol for the ores. The method referred to as the Segregation Free Analysis (SFA) was used for the determination of the parameters K and Alpha by construction of calibration curves. The method involves crushing a sufficient amount of ore so that after passing it through a set of fifteen nested screens there is sufficient material to then be split into 32 samples of mass 2-5 kg, using a riffle splitter, and analysing each of the samples. Thus, for fifteen nested screens there are fifteen series each consisting of 32 samples, making a total of 480 samples for analysis. Of the eighteen elements that were analysed in each sample only %Mn3O4, %FeO, %K2O, %P, and
%SO2 were calibrated, the first two being the main paying elements and the last three being deleterious elements for the smelting processes in which the ores are used. Calibration curves indicate that for the coarse fraction, above 1 cm, manganese ores have alpha values close to 3, whereas those less than 1 cm in diameter have alpha values closer to 1. Reasons for this behaviour are uncertain but it could be related to the behaviour of the crystal structure in the very pure ores as the ores are progressively crushed and screened to finer size fractions. Separate nomograms were therefore prepared for the coarse and fine fractions. Net conclusions indicate that both Wessels and Mamatwan ores are relatively easy to sample and that simple two or three stage processing will suffice when preparing the final 2 g aliquot at 75 microns. Apart from minor modifications in the sample preparation protocols, there is no evidence to suggest that the Wessels and Mamatwan ores require different sample preparation protocols, or that they should be assayed differently. The calibration curves for manganese ore are compared with the calibration curves for gold bearing ores which generally have alpha values close to 1. The difference in alpha between the gold ores and bulk commodities is considered to be related to the primary distribution of the metals in nature, lognormal for gold and normal for manganese.
Monitoring the lot mean and uncertainty estimates by piecewise local modelling
Authors: Minkkinen P.
Published: May 2022

Variography is an excellent tool for monitoring the long-range trend of continuous processes. Pierre Gy has presented a method that can be used for estimating the measurement variance of a lot mean as function of sampling frequency for different sampling modes: random, stratified, and systematic sample selections. The method involves the estimation of the intercept (also called the nugget effect) of the variogram at the time point zero, and numerical integration of the variogram. The method can also be used for optimising sampling plans. At the time when variography was developed on-line analysers were not available. Samples were extracted from the process streams and analysed in laboratories. It was important to optimise the sampling plans to control the analytical costs and the reliability of the plans in estimating the estimation error. For a reliable variogram more than thirty to forty samples had to be analysed. Consequently, the results could not be used on-line.

Currently process analysers are widely used to monitor continuous processes. Like in variographic estimation of the lot mean this method is based on the theory of stratified sampling. If the lot is divided into N1 strata of equal sizes (or sublots) of which n1 are sampled the variance of the lot mean aL is
[EQN]
Here s21 is the variance between strata mean values and s22 the within-strata variance, N2 is the size of strata as the potential number of samples and n2 the number of samples taken from the stratum. The great advance of stratified sampling is that only the within-strata variance propagates into the lot average if samples are taken from every stratum. With current process analysers measurements can be taken at short time intervals and that is used in the current method to estimate the process average and its variance continuously. Within a short range (or stratum in this case) a continuous process can be locally modelled with a line. With systematic sampling after a minimum of three measurements a line can be fitted to this range and the mean and variance of the range mean calculated. That is the first stratum. When the process progresses, the calculations are repeated for the new strata and values. It is important that the quality of the final lot can be monitored on-line, especially if lots of certain sizes and demanding quality specifications are produced.

The method is tested with different kinds of simulated and real data sets. This method can be easily modified also for 2D and 3D sampling targets.
Challenges in quality assurance and quality control systems development
Authors: Sukha Neressa
Published: May 2022

Quality Assurance and Quality Control (QA/QC) is of critical interest in the mining industry. Over the years, Anglo American Platinum has adopted a sound strategy of Best Practice Principles (BPP) for mass measurement, sampling, sample preparation, analysis, and metal accounting. Often, much effort is focused on implementation and maintenance of quality control systems to provide quality assurance. Within the Anglo American Platinum business units, QA/QC data are deemed of significant value on a day-to-day basis and on a higher level also provides a means to prove or disprove evaluation and metal accounting disputes between various sites and/or opposing members of the Joint Evaluation Committee (JEC). Unfortunately, QA/QC data and associated QA/QC systems alone do not always provide the technical or tangible reasons to supplement explanations around anomalies in performance. It is sometimes necessary to go beyond monitoring and focus on interpreting the QA/QC data to comprehend the underlying issues. This paper aims to showcase a multitude of actual case studies pertaining to troubleshooting of challenges encountered throughout the Platinum processing pipeline (i.e., Concentrator to Smelter to Refinery). These challenges range from areas of mass measurement to sampling, to sample preparation and analytical as well as plant performance. Observations and learnings from these instances indicated that even though stringent QA/QC was adhered to, it was evident that complying to first principles of mass measurement and sampling theory, minimum sample mass and an ongoing understanding of individual material characteristics was crucial. It was also highlighted that the re-assessment of designs, methods and protocols are necessary per material stream and that a standardization approach across all Anglo American Platinum business units is perhaps sensible at one time but may not always be appropriate and/or relevant.
Differentiating analytical error from sampling errors in PAT methods through variographic analysis
Authors: Puche J. , Romañach R. , Vega N. , Méndez R.
Published: May 2022

In variographic analysis the nugget effect provides an estimate of the total process measurement system error. The value of variographic analysis can be further increased by differentiating the analytical error from the sampling errors. The ratio of the minimum practical error (MPE) to the analytical error provides an estimate of the suitability and performance of a sampling system since the analytical error would still remain even if sampling errors could be completely eliminated. The sampling and analytical errors for four systems used to obtain 1-D lots of pharmaceutical powder blends is presented. The first studies were conducted with blends moving over a conveyor belt and with the feed-frame of a tablet press. The researchers then developed and patented a new stream sampler and chute for sampling and analysis of pharmaceutical powder blends. Near Infrared or Raman spectra were obtained as the powder blends flowed or moved and used to determine the drug concentration in the blends. Even though these methods do not require sample extraction and sample preparation in a laboratory, they are still subject to sampling errors which were estimated through the variographic analysis. The MPE was compared to the analytical error for these four systems. The results obtained show that it is often possible to reduce sampling errors to less than ten times the analytical error. These studies represent the first efforts to estimate and reduce sampling errors in the analysis of the powder blends used to manufacture the tablets that many patients take daily.
Implementation of a QAQC program for in-situ grade control by pulsed fast and thermal neutron activation methods
Authors: Reichardt Henning , Grant Ashley , Koushan Soheil , Petrovic Snezana , Dominguez Oscar
Published: May 2022

Following years of development and testing, in-situ chemical assay by Pulsed Fast and Thermal Neutron Activation (PFTNA) has been implemented in mining grade control at BHP Western Australian Iron Ore as a world first. Demonstrating the technical capability and aptness of a new methodology, however, is not sufficient to ensure the sustained quality of reported assay data. The success of moving from testing stage to implementation in active mining grade control, is chiefly dependent on the robustness of ongoing quality control and quality management.

This paper shows the steps undertaken to achieve end to end monitoring of data acquired by Blasthole Assay Tools (BHAT) using PFTNA methods. The main challenge forin situ chemical assay by the BHAT is to design a quality assurance/quality control program (QA/QC) without a physical sample being collected, and in consequence, without the conventional separation into the focus areas sample collection, sample preparation and laboratory analysis. In this context, the BHAT combines all in one in-strument, and different ways to monitor data integrity, repeatability and accuracy need to be established as outlined below.

After the validity of a BHAT calibration has been verified and a tool is in operation, data is monitored on a daily basis to check that relevant operational parameters inside the tool are working within defined acceptance limits. Measurement error in the field is monitored with repeat logs in Blastholes, and inter-instrument error by replicate logs of different BHAT units in the same Blastholes. Accuracy and instrument drift over longer periods are monitored by repeated logs in Reverse Circulation (RC) drill holes. Operational parameters, such as neutron output and spectral resolution of the instrument detector are monitored by scheduled logs in dedicated testing facilities. Also, duplicate manual sampling in Blastholes isused to compare grade populations obtained by different sampling methods in mining pits to aid grade reconciliation from mining to production. By routine application of these QA/QC steps, in conjunction with close communication of results to mining teams, the new BHAT technology has been successfully embedded in day to day mining operations.