bluuebunny/crossref_metadata_2025 huggingface dataset:
Accounting and accountability practices in the obraje of San Ildefonso of Quito: An eighteenth century productive proto-capitalist model
Authors: Rossi Roberto , Sangster Alan
Published: August 2022

The Enlightenment brought a new mercantilist discourse that stimulated new technologies of management to optimise company performance, rendering workers and production phases visible and accountable. This spread to the colonies, including Ecuador. This article uses a governmentality framework to present a case study of the Hacienda of San Ildefonso (in present-day Ecuador). Within the Hacienda, an obraje (textile workshop) was established for textile manufacturing, replacing the previous putting-out system. The obraje was based on division of labour (skilled and unskilled) involving vertical integration of the business in a proto-capitalist model. The integration of these functions within the Hacienda required the adoption of new practices of accounting to obtain more accurate control of production and workers and facilitate control at a distance. This article contributes to the literature on accounting by examining the emergence of these new practices in a unique production system developed across all Spanish America from the beginnings of its colonisation.
Understanding the Mechanism of Drug Transfer and Retention of Drug-Coated Balloons
Authors: Villar-Matamoros Estefanny , Stokes Lauren , Lloret Alyssa , Todd Meagan , Tillman Bryan W. , Yazdani Saami K.
Published: August 2022

Objective:

The purpose of this study was to determine the impact of varying inflation parameters on paclitaxel delivery and retention using a commercially available DCB.

Background:

Drug-coated balloons (DCB) have become the standard treatment for peripheral artery disease. Clinical data suggest that varying DCB delivery parameters directly impact patient outcome. Differences in delivery parameters can potentially alter the retention of the drug coating on DCBs.

Methods:

Harvested porcine carotid arteries were utilized in an ex vivo pulsatile flow bioreactor system. The DCBs were then deployed at a DCB-to-artery ratio of 1:1 or 1.25:1, an inflation time of 30 seconds or 1 minute and transit time of 30 seconds or 3 minutes. The amount of drug retention in arterial tissue was evaluated by pharmacokinetic analysis at 1 hour and 1 day post DCB deployment.

Results:

Arterial paclitaxel levels were found to be less at an inflation ratio of 1:1 with 3-minute transit time as compared to 30 seconds of transit time at 1 hour (12.3 ± 1.6 ng/mg vs. 391 ± 139 ng/mg, P = .036). At 1-day, DCBs deployed at a ratio of 1:1 resulted in less drug retention as compared to 1.25:1 (61.3 ± 23.1 ng/mg vs. 404 ± 195 ng/mg, P = .013).

Conclusion:

Arterial paclitaxel retention is reduced with extended transit times and sub-optimal expansion of the balloon. Optimization of delivery parameters can serve as an effective strategy to enhance clinical DCB outcomes.
Socially Distanced Data Collection: Lessons Learned Using Electronic Bluetooth Scales to Assess Weight
Authors: Bernhart John A. , Fellers Ashley W. , Turner-McGrievy Gabrielle , Wilson Mary J. , Hutto Brent
Published: August 2022

Introduction. Electronic Bluetooth scales (e-scales) may be useful for remote weight assessment. This study analyzed predictors of engagement with e-scales and feasibility for remote weight assessment. Method. Due to COVID-19 restrictions, participants ( n = 150, 100% African American, 79% female, average age 48.2 ± 10.6 years) in an ongoing trial were invited to receive an e-scale. Participants had 1 month to complete a weigh-in. Email, text, and phone call reminders were sent. Data were analyzed using descriptive approaches and logistic regression. Results. Seventy-five participants (50% of sample) elected to receive an e-scale. Older participants ( t = −2.01, p = .05) and a greater proportion of females (χ2 = 7.8, p < .01) signed up to receive an e-scale. An average of 2.6 ± 1.3 reminders was required. Most participants who received an e-scale completed a weigh-in ( n = 70). Discussion. Half the sample elected to receive an e-scale. Strategies to increase willingness among men and younger adults to sign up to receive an e-scale are needed.
Construct Development and Validation in Three Practical Steps: Recommendations for Reviewers, Editors, and Authors
Authors: Lambert Lisa Schurer , Newman Daniel A.
Published: August 2022

We review contemporary best practice for developing and validating measures of constructs in the organizational sciences. The three basic steps in scale development are: (a) construct definition, (b) choosing operationalizations that match the construct definition, and (c) obtaining empirical evidence to confirm construct validity. While summarizing this 3-step process [i.e., Define-Operationalize-Confirm], we address many issues in establishing construct validity and provide a checklist for journal reviewers and authors when evaluating the validity of measures used in organizational research. Among other points, we pay special attention to construct conceptualization, acknowledging existing constructs, improving existing measures, multidimensional constructs, macro-level constructs, and the need for independent samples to confirm construct validity and measurement equivalence across subpopulations.
Effective range of base isolation design parameters to improve structural performance under far and near-fault earthquakes
Authors: Sadeghi Movahhed Ataallah , Shirkhani Amir , Zardari Saeid , Noroozinejad Farsangi Ehsan , Karimi Pour Arash
Published: August 2022

Triple Friction Pendulum Isolators (TFPIs) have been widely used to enhance the seismic capacity of structures in the recent decade. This study intends to measure the effect of different Ground Motion (GM) sets, including Far-Fault (FF) and Near-Fault (NF) records, on the seismic response of the Triple Friction Pendulum (TFP) isolated structures. For this aim, different Engineering Demand Parameters (EDP), including Inter-story Drift Ratio (IDR), absolute floor acceleration, base shear, residual displacement, and damage energy are measured using numerous Nonlinear Time History (NTH) analyses. A three-dimensional mid-rise special moment resisting frames (SMFs) steel building isolated with TFPIs has been designed as per ASCE 7-16. In addition, the separate and simultaneous effect of raising the damping ([Formula: see text]) and the period ([Formula: see text]) of the base isolation system on the seismic responses of the superstructure are measured to assess the structural performance and estimate the damage energy. The [Formula: see text] and the [Formula: see text] are amplified up to 30% and 4.5 times of the superstructure period in incremental steps, respectively. The results show that the damage energy of the superstructure in the Initial Design Parameters' Values (IDPVs) of the isolator under NF records with Forward-Directivity pulses (NF-FD-GMs) is more significant than damping energy, while an inverse trend has occurred for other GM sets. Increasing the IDPVs up to a certain level reduces most EDPs and consequently causes an improvement in the seismic performance of the superstructure. The novel developed empirical relationships can be utilized as useful tools to predict IDRs and the damage states of the superstructure. The variations of the EDPs with respect to simultaneous or separate increasing the IDPVs are also reported for different GM sets.
Dam safety assessment through data-level anomaly detection and information fusion
Authors: Zhou Yuhang , Shu Xiaosong , Bao Tengfei , Li Yangtao , Zhang Kang
Published: August 2022

The anomaly detection and safety assessment of dams have attracted increasing attentions. To assess the safety of dams, a novel dam safety assessment model is proposed. The safety assessment model consists of data-level anomaly detection and information fusion. In the anomaly detection, a novel model based on the generative adversarial network and variational autoencoder is proposed. Through the stepwise training, the anomaly scores with reconstruction and discrimination losses can be obtained. Considering the multi-source and complexity of information system, a two-step fusion model is proposed. In the multi-source and multi-attribute fusion, the neighborhood rough set model is employed to construct the neighborhood granular structure. Through the idea of granular computing, the uncertainty of these sources and attributes is measured. Then the Sup-Inf fusion functions and fusion weights are employed to integrate the information. Finally, the anomaly scores with interval form are obtained. For verification, an arch dam is taken as an example. Through the analysis of detection and fusion results, the proposed model can detect the abnormal signals accurately and have the comprehensive assessment of the dam.
How does the COVID-19 pandemic impact medication adherence of patients with chronic disease?: A systematic review
Authors: Ruksakulpiwat Suebsarn , Zhou Wendie , Niyomyart Atsadaporn , Wang Tongyao , Kudlowitz Aaron
Published: August 2022

Objective

To determine how the COVID-19 pandemic impacts patients with chronic disease medication adherence.

Methods

Four electronic databases, PubMed, MEDLINE, Web of Science, and CINAHL Plus Full Text, were searched for literature between 2019 and 2021. Abstracts and later full texts were independently screened by the authors of this review using inclusion and exclusion criteria to determine relevance to our study. Joanna Briggs Institute (JBI) critical appraisal tools were used to assess the quality of included texts. Relevant information and data from the included texts were extracted into tables for data synthesis and analysis.

Results

Ten studies met the study criteria, the most popular study design was cross-sectional design (n = 9, 90.0%), others were case series (n = 1, 10.0%). Barriers to medication adherence and facilitators of medication adherence were the major two themes that participants reported regarding the impact of COVID-19 on medication adherence. Moreover, these two main themes have been organized in sub-themes that are dealt with in-depth.

Discussion

Our results could heighten healthcare providers, stakeholders, and policy leaders’ awareness of providing appropriate support for chronic disease patients, especially regarding medication adherence. Future research incorporating programs that support patients’ needs is recommended.
Unintended pregnancy and associated factors during COVID-19 pandemic in Ethiopia: Community-based cross-sectional study
Authors: Molla Wondwosen , Hailemariam Shewangizaw , Mengistu Nebiyu , Madoro Derebe , Bayisa Yesuneh , Tilahun Ruth , Wudneh Aregahegn , Ayele Getnet Melaku
Published: August 2022

Introduction:

The term ‘unintended pregnancy’ refers to a pregnancy that occurred when no children were desired or occurred earlier than desired. Unintended births account for one out of every three births in Ethiopia, and they are the leading cause of maternal morbidity and mortality. During the coronavirus disease (COVID-19) pandemic, this could be useful. COVID-19 has a significant impact on maternal health care utilization, including family planning services. As a result, this study aimed to assess unintended pregnancy and associated factors in Ethiopia during the COVID-19 pandemic.

Method:

A community-based cross-sectional study was conducted in Gedeo zone, Ethiopia, from April 1 to May 30, 2021. A simple random sampling technique was utilized to get 383 pregnant women from their respective kebeles. A structured questionnaire was used to collect data during a face-to-face interview. The data were coded, cleaned, and entered into Epidemiological Data Version 3.1 before being exported to the Statistical Package for Social Science Version 23.0 for analysis. A bivariate and multivariable logistic regression model was used to identify statistically significant associations between dependent and independent variables. The odds ratio, with a 95% confidence interval and a P value of 0.05%, was considered statistically significant.

Result:

A total of 383 pregnant women participated in the study, giving a response rate of 90.8%. During the COVID-19 pandemic, 140 (36.6%) participants stated that their current pregnancy was unintended. Unintended pregnancy was significantly associated with respondents’ age (adjusted odds ratio (AOR) = 5.214 (1.449–18.762)), primary decision maker for family planning services (AOR = 9.510 (5.057–17.887)), and fear of COVID-19 to visit a health care facility (AOR = 7.061 (2.665–18.710)).

Conclusion:

During the COVID-19 era, more than one-third of women had unintended pregnancies. Unintended pregnancy was significantly associated with respondents’ age, autonomy to use contraceptive methods, and fear of COVID-19, which required them to attend a health care institution.
Optimal and suboptimal video instructions change movement execution in young talented basketball players
Authors: Nijmeijer Eline M. , Elferink-Gemser Marije T. , Otten Egbert , Benjaminse Anne
Published: August 2022

Observational learning is considered powerful to promote (implicit) motor learning. While it is a common tool in practice, little is known about the effects of video instructions on movement execution. The aim of this study was to investigate the effects of watching biomechanically optimal (OPT) and suboptimal (SUBOPT) sidestep cutting (SSC) video instructions on movement execution. Ten male basketball players (age 15.5 ± 1.2 years, height 189.9 ± 3.1 cm, mass 75.4 ± 7.1 kg) from a Regional Talent Center performed anticipated 45° SSC tasks in baseline (BASE) followed by two counterbalanced experimental conditions. Subjects watched expert videos (matched by sex and height) of OPT and SUBOPT movement executions and were asked to imitate this to the best of their ability. Kine(ma)tic data was captured with 21 reflective markers and 2 force plates. After watching the videos, subjects displayed smaller ankle dorsiflexion angles ( p < 0.001) and greater vertical ground reaction force (vGRF) ( p = 0.012) in SUBOPT compared to OPT condition during initial contact (IC). Greater knee flexion and ankle dorsiflexion angles in the expert compared to subjects in the OPT condition were found ( p < 0.001). Contrarily, subjects were able to imitate SUBOPT executions shown by the expert. This means that athletes worsen their movement execution when modelling a SUBOPT model. Coaches are advised to mainly use (1) OPT video instructions and (2) expert modelling with a relatively small gap in movement execution between the athlete and model.
Stromal vascular fraction therapy for knee osteoarthritis: a systematic review
Authors: Boada-Pladellorens Anna , Avellanet Mercè , Pages-Bolibar Esther , Veiga Anna
Published: August 2022

Background:

Regenerative cell therapies, such as adipose-derived stromal vascular fraction (SVF), have been postulated as potential treatments for knee osteoarthritis (KOA).

Objectives:

To assess the efficacy and safety of SVF treatment against placebo and other standard therapies for treating KOA in adult patients.

Design:

A systematic review.

Data sources and methods:

We searched the following databases: MEDLINE via PubMed, Epistemonikos, PEDro, DynaMed, TripDatabase, Elsevier via Clinicalkey and Cochrane Controlled Trials Register. We included prospective interventional studies where treatment with SVF in adults with KOA was compared against placebo or other standard therapies, and results were objectively measured with at least one widely recognised osteoarthritis scale.

Results:

Among 266 studies published until May 2021, nine met our inclusion criteria. A total of 239 patients (274 knees) were included in our study. The follow-up ranged from 6 to 24 months. Six studies had a control group (only one being placebo). All studies showed that SVF improved pain and functionality measured, in most cases, with the visual analogue scale and the Western Ontario and McMaster Universities Osteoarthritis Index. In addition, five studies reported an improvement in anatomical structures, as detected in MR images. However, the number of cells contained in SVF varied substantially between different studies, which could induce a comparison bias.

Conclusion:

Although based on a small number of dissimilar studies, SVF was considered a safe treatment for KOA and could be promising in terms of pain, functionality and anatomical structure improvement. However, SVF products need to be standardised, the number of cells homogenised and the use of concomitant treatments reduced to establish proper comparisons.

Registration:

PROSPERO registration number: CRD42021284187.
Feasibility and Preliminary Safety of Smartphone-Based Automated Insulin Delivery in Adolescents and Children With Type 1 Diabetes
Authors: Deshpande Sunil , Weinzimer Stuart A. , Gibbons Kathryn , Nally Laura M. , Weyman Kate , Carria Lori , Zgorski Melinda , Laffel Lori M. , Doyle Francis J. , Dassau Eyal
Published: August 2022

Background:

A smartphone-based automated insulin delivery (AID) controller device can facilitate use of interoperable components and acceptance in adolescents and children.

Methods:

Pediatric participants (N = 20, 8F) with type 1 diabetes were enrolled in three sequential age-based cohorts: adolescents (12-<18 years, n = 8, 5F), school-age (8-<12 years, n = 7, 2F), and young children (2-<8 years, n = 5, 1F). Participants used the interoperable artificial pancreas system (iAPS) and zone model predictive control (MPC) on an unlocked smartphone for 48 hours, consumed unrestricted meals of their choice, and engaged in various unannounced exercises. Primary outcomes and stopping criteria were defined using fingerstick blood glucose (BG) data; secondary outcomes compared continuous glucose monitoring (CGM) data with preceding sensor augmented pump (SAP) therapy.

Results:

During AID, there was no more than one BG <50 mg/dL except in one young child participant; no instance of more than two episodes of BG ≥300 mg/dL lasting longer than 2 hours; and no adverse events. Despite large meals (total of 404.9 grams of carbs) and unannounced exercise (total of 182 minutes), overall CGM percent time in range (TIR) of 70 to 180 mg/dL during AID was statistically similar to SAP (63.5% vs 57.3%, respectively, P = .145). Overnight glucose standard deviation was 43 mg/dL (vs SAP 57.9 mg/dL, P = .009) and coefficient of variation was 25.7% (vs SAP 34.9%, P < .001). The percent time in closed-loop mode and connected to the CGM was 92.7% and 99.6%, respectively. Surveys indicated that participants and parents/guardians were satisfied with the system.

Conclusions:

The smartphone-based AID was feasible and safe in sequentially younger cohorts of adolescents and children.

ClinicalTrials.gov:

NCT04255381 ( https://clinicaltrials.gov/ct2/show/NCT04255381 )
eHealth policy in Spain: A comparative study between general population and groups at risk of social exclusion in Spain
Authors: Fernández Da Silva Ángela , Buceta Bran Barral , Mahou-Lago Xosé María
Published: August 2022

Background

In recent years, the healthcare sector has experienced accelerated progress in terms of the inclusion of Information and Communication Technologies (ICTs) in its procedures and formalities. However, public administrations have been unable to adapt to the peculiarities of the most vulnerable groups. This leads to marginalization of at-risk groups within the healthcare system and contributes to the widening of the so-called digital divide.

Methods

Based on the analysis of the literature, three dimensions have been constructed to identify the level of inclusion of web portals: the perception of quality, the perception of usability, and the importance attributed to their content. In order to obtain data on each of these dimensions, a study was designed based on the user test methodology as a central element (identifying and evaluating 11 vulnerable groups) and, in parallel, a survey of the general population and heuristic tests.

Results

A high percentage of vulnerable people at risk of social exclusion are not receiving adequate healthcare due to the digitalization of the system and the implementation of scarcely inclusive health web portals, which pose significant barriers in service provision for the 11 selected collectives. Meanwhile, the general population is being introduced to eHealth benefits, although the latter did not have high levels of digitization or a broad portfolio of services.

Conclusions

The general population has a relatively positive perspective of eHealth services, but only a minority of them make intensive use of them, and they are not widespread in Spain as a whole. Meanwhile, the population at risk of exclusion lacks the skills and resources to make real use of eHealth, needing “digital intermediaries” from the social sphere to achieve results. eHealth policies are not taking into account people with higher levels of marginalization, aggravating their exclusion and the digital divide.
Iatrogenic Injury to the Suprascapular Nerve Following Reverse Shoulder Arthroplasty: A Case Report
Authors: Long Jason , Liles Jordan , Anakwenze Oke , Klifto Christopher
Published: August 2022

The location and course of the suprascapular nerve (SSN) to the glenohumeral joint places this nerve at risk when operating around the shoulder. Iatrogenic injury to the suprascapular nerve has been described in several different procedures including, rotator cuff repairs, posterior capsulorraphy, Bankart repairs, SLAP lesion repairs, Latarjet procedures, and shoulder arthroplasty. We present a case of iatrogenic suprascapular nerve injury due to superior glenoid baseplate screw placement following primary reverse shoulder arthroplasty (RSA), a novel approach to diagnosis of nerve injury, and treatment.
Regulation by impasse: Pesticide registration, capital and the state in Costa Rica
Authors: Castro-Vargas María Soledad , Werner Marion
Published: August 2022

Costa Rica's prodigious use of pesticides, as well as the burgeoning plantation sector that these agrochemicals support, exacerbates the tensions between extraction and preservation at the heart of the country's development model. We explore these tensions through a study of the country's pesticide registry, the regulatory process to approve active ingredients and formulations for use. After nearly two decades of reform efforts, the registry is widely recognized to be non-functioning: most of the country's pesticides exist in administrative limbo and relatively few new compounds have been approved. Based on extensive interviews and in-depth policy analysis, we construct four phases of reform and use a strategic-relational approach to the state to analyze this process. We conceptualize the registry's gridlock as a form of governance that we term regulation by impasse, an arrangement reproduced through disputes within and between the cognizant ministries, juridical bodies and other regulating authorities, in relation to the shifting strategies and contexts of political economic and wider social forces. We argue that hegemony is tenuously maintained through the registry dispute itself, while revealing the deeply frayed condition of the Costa Rican development model.
Technical reform or radical justice? Environmental discourse in non-governmental organizations
Authors: Ritter Ellie , Thaler Gregory M
Published: August 2022

Discourses integrate facts, frames, metaphors, and narratives to produce shared understandings of environmental problems, and these shared understandings structure environmental policy and outcomes. Recent scholarship uses new data and quantitative content analysis to identify Environmental Management, Climate Politics, Ecological Modernization, and Environmental Justice as the major discourses among global environmental non-governmental organizations (ENGOs). Such discourse classification can be intellectually and politically useful, but typologies elide variation. Understanding environmental discourse involves not only classifying major discourses, but also identifying nuances, tensions, and absences behind any typology. This study builds on recent quantitative research with a qualitative, small-N design. We selected two ENGOs identified as extreme representatives of each of the four major discourses, for a total of eight ENGOs, and we conducted qualitative content analysis of ENGO documents as the basis for critical discourse analysis (CDA), examining the principal ideas, frames, and narratives of each discourse and the relations between discourses. Our analysis identifies tensions in Climate Politics between climate justice and multi-stakeholder governance subdiscourses, and divergence in Environmental Management discourse between protection-based and market-based approaches. Linking discourse with organizational structure, we trace tensions in these categories to broader webs of power that transcend typological classifications. Qualitative case studies both deepen and challenge quantitative analyses, underlining the importance of multimethod research and enhancing our understanding of environmental discourse as a key sphere of environmental politics.
Safety and efficacy of classical complement pathway inhibition with sutimlimab in chronic immune thrombocytopenia
Authors: Broome Catherine M. , Röth Alexander , Kuter David J. , Scully Marie , Smith Roy , Wang Jennifer , Reuter Caroline , Hobbs William , Daak Ahmed
Published: August 2022

Chronic/refractory immune thrombocytopenia (ITP) is a rare and pathophysiologically heterogeneous disorder with variable responsiveness to available treatments. Sutimlimab, a first-in-class humanized monoclonal anti-C1s IgG4 antibody, selectively inhibits the classical pathway. This phase 1 study (NCT03275454) assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of biweekly sutimlimab in patients with chronic/refractory ITP with an inadequate response to ≥2 therapies (platelet count ≤ 30 × 109/L). Twelve patients (median age 42 years) received sutimlimab for a median of 20.5 weeks followed by a median 2-week washout period (part A). In part B, 7 of the 12 eligible patients received sutimlimab retreatment for a median of 113 weeks. In part A, the mean (standard deviation) platelet count increased from 25 × 109/L (17) to 54 × 109/L (60) 24 hours after starting sutimlimab, maintaining ≥50 × 109/L throughout part A. Five patients (42%) achieved durable platelet count responses (≥50 × 109/L in ≥50% of follow-up visits) and 4 achieved complete response (platelet count ≥100 × 109/L). The mean platelet count returned to baseline during washout and increased upon retreatment in part B. The mean platelet count improvements accompanied the rapid inhibition of the classical pathway. There were 74 treatment-emergent adverse events in part A (n = 10) and 70 in part B (n = 6). Five serious adverse events were observed; 1 event (migraine) was assessed by the investigator as related to sutimlimab. These results demonstrated that in some patients with ITP, autoantibodies activate the classical complement pathway, accelerating platelet destruction or impairing platelet production and contributing to treatment failure. Thus, C1s inhibition may be a safe and beneficial therapeutic approach for patients with chronic/refractory ITP.
Targeted therapy with the mutant IDH2 inhibitor enasidenib for high-risk IDH2-mutant myelodysplastic syndrome
Authors: DiNardo Courtney D. , Venugopal Sangeetha , Lachowiez Curtis , Takahashi Koichi , Loghavi Sanam , Montalban-Bravo Guillermo , Wang Xuemei , Carraway Hetty , Sekeres Mikkael , Sukkur Ameenah , Hammond Danielle , Chien Kelly , Maiti Abhishek , Masarova Lucia , Sasaki Koji , Alvarado Yesid , Kadia Tapan , Short Nicholas J. , Daver Naval , Borthakur Gautam , Ravandi Farhad , Kantarjian Hagop M. , Patel Bhumika , Dezern Amy , Roboz Gail , Garcia-Manero Guillermo
Published: August 2022

The isocitrate dehydrogenase enzyme 2 (IDH2) gene is mutated in ∼5% of patients with myelodysplastic syndrome (MDS). Enasidenib is an oral, selective, mutant IDH2 inhibitor approved for IDH2-mutated (mIDH2) relapsed/refractory acute myeloid leukemia. We designed a 2-arm multicenter study to evaluate safety and efficacy of (A) the combination of enasidenib with azacitidine for newly diagnosed mIDH2 MDS, and (B) enasidenib monotherapy for mIDH2 MDS after prior hypomethylating agent (HMA) therapy. Fifty patients with mIDH2 MDS enrolled: 27 in arm A and 23 in arm B. Median age of patients was 73 years. The most common adverse events were neutropenia (40%), nausea (36%), constipation (32%), and fatigue (26%). Hyperbilirubinemia from off-target UGT1A1 inhibition occurred in 14% of patients (8%; grades 3 and 4), and IDH-inhibitor–associated differentiation syndrome (IDH-DS) in 8 patients (16%). In the combination arm, the overall response rate (ORR: complete remission [CR] + marrow CR [mCR] + partial remission) was 74%, including 70% composite CR (CRc: CR + mCR). Median time to best response was 1 month (range, 1-4), and a median of 4 cycles was received (1-32). The median overall survival (OS) was 26 months (range, 14 to not reached). In the enasidenib monotherapy cohort after HMA failure, ORR and CRc were both 35% (n = 8), with 22% CR (n = 5). Median time to first response was 27 days, and time to best response was 4.6 months (2.7-7.6 months). A median of 7 cycles was received (range, 1-29), and the median OS was 20 months (range, 11 to not reached). Enasidenib is an effective treatment option for mIDH2 MDS, both in combination with azacitidine for treatment-naïve high-risk MDS, and as a single agent after prior HMA therapy. This trial is registered at www.clinicaltrials.gov as #NCT03383575.
Blood titanium levels in patients with large and sliding titanium implants
Authors: Tognini Martina , Hothi Harry , Tucker Stewart , Broomfield Edel , Shafafy Masood , Gikas Panos , Di Laura Anna , Henckel Johann , Hart Alister
Published: August 2022

Background

Titanium, which is known to be a highly biologically inert element, is one of the most commonly used metals in orthopaedic implants. While cobalt and chromium blood metal ion testing is routinely used in the clinical monitoring of patients with metal-on-metal hip implants, much less is known about the levels of titanium in patients with other implant types. The aim of this study was to better understand the normal ranges of blood titanium levels in patients implanted with large and sliding titanium constructs by comparison with reference levels from conventional titanium hips.

Methods

This study examined data collected from 136 patients. Over a period of 24 months, whole blood samples were collected from 41 patients implanted with large titanium implants: long (range 15 to 30 cm) spine rods with a sliding mechanism (“spine rods”, n = 18), long bone tumour implants (“tumour implants”, n = 13) and 3D-printed customised massive acetabular defect implants (“massive acetabular implants”, n = 10). This data was compared with standard, uncemented primary titanium hip implants (“standard hips”, 15 cm long) (n = 95). Clinical, imaging and blood titanium levels data were collected for all patients and compared statistically between the different groups.

Results

The median (range) of blood titanium levels of the standard hip, spine rods, femoral tumour implants and massive acetabular implants were 1.2 ppb (0.6–4.9), 9.7 ppb (4.0–25.4), 2.6 ppb (0.4–104.4) and 5.7 ppb (1.6–31.5) respectively. Spine rods and massive acetabular implants had significantly greater blood titanium levels compared to the standard hips group (p < 0.001).

Conclusion

This study showed that titanium orthopaedic implants that are large and/or have a sliding mechanism have higher blood titanium levels compared to well-functioning, conventionally sized titanium hips. Reassuringly, the increased levels did not appear to induce adverse metal reactions. This study provides useful baseline data for future studies aimed at assessing blood titanium levels as a biomarker for implant function.
The concept of vulnerability in aged care: a systematic review of argument-based ethics literature
Authors: Sanchini Virginia , Sala Roberta , Gastmans Chris
Published: August 2022

Background

Vulnerability is a key concept in traditional and contemporary bioethics. In the philosophical literature, vulnerability is understood not only to be an ontological condition of humanity, but also to be a consequence of contingent factors. Within bioethics debates, vulnerable populations are defined in relation to compromised capacity to consent, increased susceptibility to harm, and/or exploitation. Although vulnerability has historically been associated with older adults, to date, no comprehensive or systematic work exists on the meaning of their vulnerability. To fill this gap, we analysed the literature on aged care for the meaning, foundations, and uses of vulnerability as an ethical concept.

Methods

Using PRISMA guidelines, we conducted a systematic review of argument-based ethics literature in four major databases: PubMed, Embase®, Web of Science™, and Philosopher’s Index. These covered biomedical, philosophy, bioethical, and anthropological literature. Titles, abstracts, and full texts of identified papers were screened for relevance. The snowball technique and citation tracking were used to identify relevant publications. Data analysis and synthesis followed the preparatory steps of the coding process detailed in the QUAGOL methodology.

Results

Thirty-eight publications met our criteria and were included. Publication dates ranged from 1984 to 2020, with 17 publications appearing between 2015 and 2020. Publications originated from all five major continents, as indicated by the affiliation of the first author. Our analyses revealed that the concept of vulnerability could be distinguished in terms of basic human and situational vulnerability. Six dimensions of older adults’ vulnerability were identified: physical; psychological; relational/interpersonal; moral; sociocultural, political, and economic; and existential/spiritual. This analysis suggested three ways to relate to older adults’ vulnerability: understanding older adults’ vulnerability, taking care of vulnerable older adults, and intervening through socio-political-economic measures.

Conclusions

The way in which vulnerability was conceptualised in the included publications overlaps with distinctions used within contemporary bioethics literature. Dimensions of aged care vulnerability map onto defining features of humans, giving weight to the claim that vulnerability represents an inherent characteristic of humans. Vulnerability is mostly a value-laden concept, endowed with positive and negative connotations. Most publications focused on and promoted aged care, strengthening the idea that care is a defining practice of being human.
Management of human resources for health: implications for health systems efficiency in Kenya
Authors: Nyawira Lizah , Tsofa Benjamin , Musiega Anita , Munywoki Joshua , Njuguna Rebecca G. , Hanson Kara , Mulwa Andrew , Molyneux Sassy , Maina Isabel , Normand Charles , Jemutai Julie , Barasa Edwine
Published: August 2022

Background

Human resources for health consume a substantial share of healthcare resources and determine the efficiency and overall performance of health systems. Under Kenya’s devolved governance, human resources for health are managed by county governments. The aim of this study was to examine how the management of human resources for health influences the efficiency of county health systems in Kenya.

Methods

We conducted a case study using a mixed methods approach in two purposively selected counties in Kenya. We collected data through in-depth interviews (n = 46) with national and county level HRH stakeholders, and document and secondary data reviews. We analyzed qualitative data using a thematic approach, and quantitative data using descriptive analysis.

Results

Human resources for health in the selected counties was inadequately financed and there were an insufficient number of health workers, which compromised the input mix of the health system. The scarcity of medical specialists led to inappropriate task shifting where nonspecialized staff took on the roles of specialists with potential undesired impacts on quality of care and health outcomes. The maldistribution of staff in favor of higher-level facilities led to unnecessary referrals to higher level (referral) hospitals and compromised quality of primary healthcare. Delayed salaries, non-harmonized contractual terms and incentives reduced the motivation of health workers. All of these effects are likely to have negative effects on health system efficiency.

Conclusions

Human resources for health management in counties in Kenya could be reformed with likely positive implications for county health system efficiency by increasing the level of funding, resolving funding flow challenges to address the delay of salaries, addressing skill mix challenges, prioritizing the allocation of health workers to lower-level facilities, harmonizing the contractual terms and incentives of health workers, and strengthening monitoring and supervision.
SINFONIA study protocol: a phase II/III randomised controlled trial examining benefits of guided online group singing in people with chronic obstructive pulmonary disease and interstitial lung disease and their carers
Authors: Smallwood Natasha , Pascoe Amy , Vogrin Sara , Philip Jennifer
Published: August 2022

Background

Chronic obstructive pulmonary disease (COPD) and interstital lung disease (ILD) are incurable conditions characterised by airflow limitation, persisting respiratory symptoms, and progressive respiratory failure. People living with COPD or ILD often suffer from chronic and severe breathlessness, with limited treatment options and low engagement rates with current therapies. Group singing represents a potential community-based therapy to improve quality of life for patients with COPD or ILD and breathlessness.

Methods

This protocol papers describes SINFONIA, a parallel, double-arm, randomised, blinded-analysis, mixed-methods phase II/III trial of guided, online group singing that will be conducted over 24 months. Adults with confirmed COPD or ILD, on stable treatment for at least four weeks at time of recruitment, with a modified Medical Research Council (mMRC) dyspnoea score of two or greater, who are capable and willing to give consent, and not currently participating in pulmonary rehabilitation will be eligible to participate. Carers may optionally enrol in the trial. Data will be collected on quality of life, anxiety and depression, breathlessness, mastery of breathing, exercise tolerance, loneliness, healthcare utilisation, and carer quality of life (optional). Participants will be randomised 1:1 to intervention or control arms with intervention arm attending one 90 min, guided, online, group singing session per week for 12 weeks and control arm continuing routine care. Phase II of the trial aims to determine the feasibility and acceptability of guided, online group singing and will collect preliminary data on effectiveness. Phase III aims to determine whether guided, online group singing has an effect on quality of life with the primary outcome being a between arm difference in quality of life (36-item Short Form Survey) measured at 12 weeks.

Discussion

SINFONIA is the first study is the first of its kind in Australia and to our knowledge, the first to deliver the singing intervention program entirely online. Determining the feasibility, acceptability, and effectiveness of guided, online group singing is an important step towards improving low-cost, low-risk, community-based therapeutic options for patients living with COPD or ILD and breathlessness.

Trial registration: Phase II—ACTRN12621001274864, registered 20th September 2021; Phase III—ACTRN12621001280897, registered 22nd September 2021.
Netrin-1 induces the anti-apoptotic and pro-survival effects of B-ALL cells through the Unc5b-MAPK axis
Authors: Huang Lan , An Xizhou , Zhu Yao , Zhang Kainan , Xiao Li , Yao Xinyuan , Zeng Xing , Liang Shaoyan , Yu Jie
Published: August 2022

Background

B-cell acute lymphoblastic leukemia (B-ALL) comprises over 85% of all acute lymphoblastic leukemia (ALL) cases and is the most common childhood malignancy. Although the 5 year overall survival of patients with B-ALL exceeds 90%, patients with relapsed or refractory B-ALL may suffer from poor prognosis and adverse events. The axon guidance factor netrin-1 has been reported to be involved in the tumorigenesis of many types of cancers. However, the impact of netrin-1 on B-ALL remains unknown.

Methods

The expression level of netrin-1 in peripheral blood samples of children with B-ALL and children without neoplasia was measured by enzyme-linked immunosorbent assay (ELISA) kits. Then, CCK-8 cell proliferation assays and flow cytometric analysis were performed to detect the viability and apoptosis of B-ALL cells (Reh and Sup B15) treated with exogenous recombinant netrin-1 at concentrations of 0, 25, 50, and 100 ng/ml. Furthermore, co-immunoprecipitation(co-IP) was performed to detect the receptor of netrin-1. UNC5B expression interference was induced in B-ALL cells with recombinant lentivirus, and then CCK-8 assays, flow cytometry assays and western blotting assays were performed to verify that netrin-1 might act on B-ALL cells via the receptor Unc5b. Finally, western blotting and kinase inhibitor treatment were applied to detect the downstream signaling pathway.

Results

Netrin-1 expression was increased in B-ALL, and netrin-1 expression was upregulated in patients with high- and intermediate-risk stratification group of patients. Then, we found that netrin-1 induced an anti-apoptotic effect in B-ALL cells, implying that netrin-1 plays an oncogenic role in B-ALL. co-IP results showed that netrin-1 interacted with the receptor Unc5b in B-ALL cells. Interference with UNC5B was performed in B-ALL cells and abolished the antiapoptotic effects of netrin-1. Further western blotting was applied to detect the phosphorylation levels of key molecules in common signaling transduction pathways in B-ALL cells treated with recombinant netrin-1, and the FAK-MAPK signaling pathway was found to be activated. The anti-apoptotic effect of netrin-1 and FAK-MAPK phosphorylation was abrogated by UNC5B interference. FAK inhibitor treatment and ERK inhibitor treatment were applied and verified that the FAK-MAPK pathway may be downstream of Unc5b.

Conclusion

Taken together, our findings suggested that netrin-1 induced the anti-apoptotic effect of B-ALL cells through activation of the FAK-MAPK signaling pathway by binding to the receptor Unc5b.
Magnitude and determinants of suicide among overweight reproductive-age women, Chacha and Debre Berhan Town, Ethiopia: community based cross-sectional study
Authors: Engda Abayneh Shewangzaw , Belete Habte , Wubetu Abate Dargie , Engidaw Nigus Alemnew , Amogne Fetene Kasahun , Kitaw Tebabere Moltot , Bete Tilahun , Kebede Worku Misganaw , Atinafu Bantalem Tilaye , Demeke Solomon Moges
Published: August 2022

Background

The magnitude and impact of women's suicidal behaviors, like suicidal ideation and suicidal attempts, are an important public health problem in low and middle-income countries, including Ethiopia. Suicidal behavior and being overweight are typical complications of reproductive age with many undesired consequences. Despite both having a serious impact on women of reproductive age, they are neglected in Ethiopia. Accordingly, this study aimed to examine the magnitude and determinants of suicide among overweight reproductive-age women in Chacha and Debre Berhan towns, Ethiopia.

Methods

A community-based cross-sectional study design was once employed from April 1, 2020 to June 1, 2020. The Composite International Diagnostic Interview was used to measure suicidal attempts and ideation, and the data was collected by direct interview. All collected data were entered into Epi Data version 4.6 and analyzed with SPSS version 25. Bivariate and multivariable regression models were used to determine the factors associated with a suicidal attempt and ideation. A p-value of less than 0.05 was considered statistically significant.

Result

Of the total participants, 523 were included, with a response rate of 93.7%. The prevalence of suicidal ideation was 13.0% (95% CI 10.1–15.9), whereas suicidal attempt was 2.3% (95% CI 1.1–3.6). Based on multivariable regression analysis, the odds of suicidal ideation have been higher among overweight women with stressful life events, depression, and younger age groups.

Conclusion

Suicidal ideation was frequent in overweight reproductive-age women. Preventing, treating, and using coping mechanisms regarding identified factors is a good way to minimize the burden of suicide.
Genotype–phenotype associations within the Li-Fraumeni spectrum: a report from the German Registry
Authors: Penkert Judith , Strüwe Farina J. , Dutzmann Christina M. , Doergeloh Beate B. , Montellier Emilie , Freycon Claire , Keymling Myriam , Schlemmer Heinz-Peter , Sänger Birte , Hoffmann Beatrice , Gerasimov Tanja , Blattmann Claudia , Fetscher Sebastian , Frühwald Michael , Hettmer Simone , Kordes Uwe , Ridola Vita , Kroiss Benninger Sabine , Mastronuzzi Angela , Schott Sarah , Nees Juliane , Prokop Aram , Redlich Antje , Seidel Markus G. , Zimmermann Stefanie , Pajtler Kristian W. , Pfister Stefan M. , Hainaut Pierre , Kratz Christian P.
Published: August 2022

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by pathogenic TP53 variants. The condition represents one of the most relevant genetic causes of cancer in children and adults due to its frequency and high cancer risk. The term Li-Fraumeni spectrum reflects the evolving phenotypic variability of the condition. Within this spectrum, patients who meet specific LFS criteria are diagnosed with LFS, while patients who do not meet these criteria are diagnosed with attenuated LFS. To explore genotype–phenotype correlations we analyzed 141 individuals from 94 families with pathogenic TP53 variants registered in the German Cancer Predisposition Syndrome Registry. Twenty-one (22%) families had attenuated LFS and 73 (78%) families met the criteria of LFS. NULL variants occurred in 32 (44%) families with LFS and in two (9.5%) families with attenuated LFS (P value < 0.01). Kato partially functional variants were present in 10 out of 53 (19%) families without childhood cancer except adrenocortical carcinoma (ACC) versus 0 out of 41 families with childhood cancer other than ACC alone (P value < 0.01). Our study suggests genotype–phenotype correlations encouraging further analyses.