Terms Of Impact Research Articles

Implementation of a methodology to assess patient reported outcomes in lung cancer patients: The PeOpLe (Patient-reported Outcomes in Lung cancer) study protocol

ObjectiveThe purpose of this article is to describe the PeOpLe study protocol, developed to assess patient-reported health outcomes in advanced or metastatic non-small-cell lung cancer in routine clinical practice using the methodology provided by the International Consortium for Health Outcomes Measurement tool. MethodThe study envisaged will be multicenter, longitudinal, ambispective and observational. Two groups will be compared: a control group (followed up according to standard clinical practice) and an experimental group (followed up using the International Consortium for Health Outcomes Measurement methodology adapted to the Spanish setting for 6 months). The variables collected will be related to demography (age, sex, degree of family support), clinical factors (smoking, comorbidities, lung capacity), the neoplasm (histology, staging, mutations), pharmacotherapy (treatment schedule, modifications, and complications), health status (functional status, quality of life, satisfaction and overall survival) and resource consumption (emergency visits, hospital admissions and time spent by health providers). The PeOpLe study protocol has been approved by the Ethics Committee for Research into Medicinal Products of the Gregorio Marañón General University Hospital and will be conducted in compliance with prevailing ethical principles and standards. ConclusionsThe PeOpLe study will explore how patient-reported outcomes collection can be developed and integrated with the clinical processes used in the management of patients with locally advanced or metastatic non-small cell lung cancer what patient-reported outcomes can be measured with systems that can conveniently be used both by patients and by healthcare providers. Systematic evaluation of patient-reported outcomes will help determine their impact in terms of effectiveness (survival), safety (complications of systemic therapy), and quality of life and patient satisfaction. The multidisciplinary and multicenter nature of the study will facilitate a comprehensive view of the subject analyzed and allow external reproducibility.

Utility of Next-Generation Sequencing in the Detection of RNA Fusion Genes in Myeloid Malignancies in Singapore

Background Oncogenic fusion genes play an instrumental role in the pathogenesis of haematological malignancies and the identification of these genes is crucial for diagnosis, risk stratification and treatment decisions. Conventional diagnostic methods such as karyotyping and fluorescence in situ hybridization (FISH) are the current standard of care but are limited in the sensitivity and availability of different FISH probes for detection of fusion genes. In our institution, we have routinely integrated a targeted next-generation sequencing (NGS) panel in our diagnostic workflow for patients with suspected myeloid malignancies. Here we aim to review the cases with RNA fusion genes detected via NGS and compare these results with that of conventional diagnostic methods. Methods We analysed bone marrow samples from patients with suspected myeloid malignancies at the time of diagnosis in Singapore General Hospital (SGH). Extracted genomic DNA and RNA were amplified, and library preparation was performed with the Oncomine TM Myeloid Research assay (Thermo Fisher Scientific) to interrogate 40 DNA genes and 29 fusion driver genes. NGS libraries were sequenced on the Ion GeneStudio S5 System (Thermo Fisher Scientific) and analyzed using in-house bioinformatics pipelines and the Ion Reporter software. Limit of detection was determined as 3% allele frequency for DNA variants and 10 -2 for RNA fusions. RNA fusions detected by the NGS panel were consolidated and compared with cytogenetics (karyotyping and FISH) results. Results A total of 436 samples from adult patients with suspected myeloid malignancies were received for NGS testing from October 2021 to March 2023 in SGH, the largest tertiary hospital in Singapore. 306 had paired cytogenetics and NGS testing performed. 27 of the 306 cases (9%) had RNA fusions detected by NGS as summarized in Table 1 and Figure 1; their disease subgroups comprised of 16 acute myeloid leukaemia (AML), 5 chronic myeloid leukaemia (CML), 3 BCR-ABL1-negative myeloproliferative neoplasm (MPN), 2 acute promyelocytic leukaemia (APL) and 1 myelodysplastic syndrome (MDS). Eight AML cases had RUNX1-RUNX1T1.R3R3 fusions, with 6/8 (75%) harbouring additional DNA single nucleotide variants or indel mutations. Two AML cases had CBFB-MYH11 fusions, with 1 associated with KIT D419 deletion, and the other with U2AF1, NF1, and ASXL1 mutations. We also identified 2 adult AML cases (aged 49 and 65 years respectively) with DEK-NUP214.D9N18 fusions, both of which had associated FLT3-ITD mutations. There were 5 cases with KMT2A fusions, with a variety of partners including MLLT3.K9M6 (n=2), ELL.K9E2 (n=1), MLLT1.K8M4 (n=1), and MLLT6.K8M9 (n=1). Two patients with APL had PML-RARA detected for different variants: P3R3 and P6R3. Amongst the 8 MPN cases, 5 had BCR-ABL1 fusions consistent with diagnosis of CML. There was 1 case of MPN-Eo with FLP1L1-PDGFRA fusion, and the remaining 2 with ETV6-ABL1 and KMT2A-ELL.K9E2 rare fusions. The detected RNA fusions had clinical impact in establishing diagnosis (93%), prognosis (96%), and guidance of treatment decisions (89%). Out of the 27 cases with RNA fusions detected by NGS, 23 (85%) had concordant karyotype and FISH results. Four RNA fusions, namely KMT2A-ELL, CBFB-MYH11, FIP1L1-PDGFRA and ETV6-ABL1, were not detected by karyotyping or conventional FISH probes performed in our institution. It likely reflects the sensitivity of the NGS panel in detecting RNA fusions in cases of cryptic translocations. Conclusion We have demonstrated that NGS has a high sensitivity for identification of RNA fusion genes, is complementary to conventional cytogenetics testing, and has vast clinical impact in terms of diagnosis, prognostication and clinical management. We advocate for the integration of NGS with DNA and RNA sequencing into routine investigation of suspected myeloid malignancies for a more precise and comprehensive diagnostic approach.

Impact of MTHFR Polymorphisms C677T and A1298C in Acute Lymphoblastic Leukemia and Burkitt Lymphoma Patients Exposed to Methotrexate and Asparaginase

Background: Asparaginase (Asp) and high-dose methotrexate (HDMTX) are pivotal drugs in the treatment of aggressive hematological malignancies as acute lymphoblastic leukemia (ALL) and Burkitt lymphoma (BL). Asp and MTX present specific drug-related toxicities; for Asp, prothrombotic alteration of the coagulation profile, hepatobiliary and pancreatic toxicities, for MTX, renal, hepatobiliary, hematologic, gastro-intestinal and neuro- toxicity. The 5,10-methylenetetrahydrofolate reductase (MTHFR) is the enzyme involved in conversion of homocysteine into methionine. MTHFR most frequent single nucleotide polymorphisms C677T and A1298C are associated with reduced enzymatic activity up to 60%, that implies hyperhomocysteinemia and increased toxicity of MTX. Numerous studies have explored the relationship between C677T and A1298C polymorphisms of MTHFR and MTX toxicity and/or outcome in children ALL, but results are controversial. Nevertheless, it is common practice to reduce MTX dosage in adult patients in homozygosis. Aims: To explore the relationship between the MTHFR C677T and A1298C polymorphisms in homozygosis and development of MTX toxicity in a cohort of adult patients; furthermore, to evaluate the relationship with thrombotic risk in patients exposed to Asp. Materials and Methods: Data from consecutive adult onco-hematologic patients for whom MTHFR C677T and A1298C polymorphism analysis was available, treated with chemotherapeutic regimens containing HDMTX and/or Asp was retrospectively collected at a single center Italian institution. Adverse events (AEs) were graded according to CTCAE 5.0. Statistical analysis was performed with R language. The impact of MTHFR polymorphisms was evaluated by mean of a multivariate analysis adjusting Odds Ratio (OR) estimates for drug dosage and disease status. Results: Data from 78 patients, 57 affected by ALL, 3 by mixed phenotype leukemia (MPAL) and 18 by BL, was retrospectively collected. Overall, 13 (16.7%) of patients were 677TT and 8 (10.3%) were 1298CC. Patients with ALL/MPAL received mostly pediatric-inspired chemotherapy regimens (containing MTX 2.5 - 5 g/m 2 and Asp 1000-2000 UI/m 2), patients with BL received modified Rituxumab (R)-BFM protocol (MTX 1.5 g/m2); age/comorbidities-adjusted dose reduction was performed according to institutional guidelines. Median age for ALL and BL patients was 37.5 (IQR 27.0-54.2) and 33.5 (26.0-49.7) years, respectively; 54/78 (69.2%) of patients were male. Patients received a median of 3 (IQR 2-6) cycles containing HDMTX and/or Asp, for a total number of 299 cycles (94 containing Asp, 184 HDMTX and 24 both); 142 (48.0%) cycles were administered for active disease (AD), at diagnosis/relapse, and 154 (52.0%) in complete remission (CR). The impact of different dosages of Asp < 1000 UI/m 2 and ≥ 1000 UI/m² and of HDMTX <1.5 g/m 2 and ≥ 1.5 g/m 2 as well as the impact of disease status (AD vs CR) on AEs was explored. Concerning Asp therapy and thrombotic risk, 13 deep vein thrombosis (DVT) were observed, but no association between 677TT nor 1298CC was appreciated. AD status was strongly related to DVT (21.4% vs 1.8%, p 0.003). Coherently with the MTHFR-independent drug's mechanism of action, the polymorphisms had no impact on the development of Asp-related toxicities. Diversely, concerning HDMTX, in multivariate analysis, patients with 677TT were more likely to experience AST increase grade ≥3 (OR 10.55, 95%CI 1.34-83.09) while a protective role versus any grade GGT increase was observed (OR 0.09, 95%CI 0.01-0.71) (Figure 1A). Patients with 1298CC exhibited a superior incidence any grade AST/ALT increase, not confirmed for grade ≥3 (Figure 1B). No significant superior toxicity was observed in terms of renal, gastro-intestinal, hematologic AEs. The impact of a MTX dose reduction >25% of expected dose was then explored in a homogeneous population of 45 front-line pediatric-regimen treated ALL patients (35 received MTX dose ≥75% and 10 < 75%) and no impact in terms of OS and RFS was appreciated. Conclusions: The analysis ofMTHFR polymorphisms in adult patients is useful in identifying patients at higher risk for transaminitis, providing a biological parameter to integrate with hepatosteatosis, liver stiffness evaluation and BMI, for a comprehensive hepatic baseline evaluation. Patients at higher risk for hepatic complications may benefit from MTX dose reduction with no impact on disease outcome.

Adaptive finite-time prescribed performance tracking control for hydraulic servo systems with friction compensation

Hydraulic systems present numerous challenges in the development of high-performance tracking controllers due to their highly nonlinear characteristics and heavy modeling uncertainties. Addressing this issue, this paper presents a friction compensation-based finite-time tracking control strategy with prescribed performance constraints. The system model is first derived, taking into consideration the nonlinear behaviors and potential uncertainties encountered in practical scenarios. Then, an adaptive finite-time prescribed performance controller is synthesized based on the backstepping framework. A novel form of finite-time performance function is introduced to constrain the tracking error, which provides the closed-loop system with a less complex guarantee of finite-time convergence and can also deliver the required transient performance and steady-state accuracy. Additionally, given the impact of uncertainty terms and the difficulty in obtaining the virtual command derivative, we employ neural networks (NNs) to estimate unknown dynamics and introduce command filters to acquire the intermediate signals, simplifying the backstepping control design process. Theoretical analysis indicates that the proposed control strategy can achieve the desired tracking performance and ensure the stability of the entire closed-loop system. Comparative numerical simulations are presented to confirm the usefulness of the suggested approach.

Ten Years After Mass Treatment with Two Doses of Azithromycin for Trachoma Elimination in Rombo District – Kilimanjaro: Is Trachoma Still Eliminated? A Case Study of Kahe Mpya Sub-Village

Purpose: This study aimed at evaluating the long term impact of mass distribution of azithromycin in a community which had high prevalence of trachoma and documenting the current prevalence of trachoma. Material and Methods: All residents of Kahe Mpya were given chance to participate in this study, in turn 575 residents participated. The conjunctiva of each consenting resident was examined for clinical signs of trachoma using WHO trachoma grading scheme. Results: The overall prevalence of active trachoma was 4.7% versus 8.1% found 10 years back after the second dose of azithromycin and 3.4% during the elimination period in 2005. In children < 10 years of age the prevalence of active trachoma was 3.3% versus 16.3% found after the second dose of azithromycin and 2.6% during elimination. Children < 10 years of age carry the majority (70%) of the active disease. TS, TT and CO were 109(19%) cases, 7(1.2%) cases and 2(0.3%) cases respectively, and almost all of these cases were in the age group older than 30 years. Conclusion: The prevalence of trachoma fell dramatically during the interventions period and continued to be low ten years after mass azithromycin distribution. Trachoma is still eliminated in this community. Complications of trachoma (TT and TS) still continue to develop.

Pilot Study: Short Term Impact of Radiation Therapy on Bone Mineral Density and Bone Metabolism

Despite the risk of complications, high dose radiation therapy is increasingly utilized in the management of selected bone malignancies. In this study, we investigate the impact of moderate to high dose radiation (over 50 Gy) on bone metabolism and structure. Between 2015 and 2018, patients with a primary malignant bone tumor of the sacrum that were either treated with high dose definitive radiation only or a combination of moderate to high dose radiation and surgery were prospectively enrolled at a single institution. Quantitative CTs were performed before and after radiation to determine changes in volumetric bone mineral density (BMD) of the irradiated and non-irradiated spine. Bone histomorphometry was performed on biopsies of the irradiated sacrum and the non-irradiated iliac crest of surgical patients using a quadruple tetracycline labeling protocol. In total, 9 patients were enrolled. Two patients received radiation only (median dose 78.3 Gy) and 7 patients received a combination of preoperative radiation (median dose 50.4 Gy), followed by surgery. Volumetric BMD of the non-irradiated lumbar spine did not change significantly after radiation, while the BMD of the irradiated sacrum did (pre-radiation median: 108.0 mg/cm3 (IQR 91.8–167.1); post-radiation median: 75.3 mg/cm3 (IQR 57.1–110.2); p = 0.010). The cancellous bone of the non-irradiated iliac crest had a stable bone formation rate, while the irradiated sacrum showed a significant decrease in bone formation rate [pre-radiation median: 0.005 mm3/mm2/year (IQR 0.003–0.009), post-radiation median: 0.001 mm3/mm2/year (IQR 0.001–0.001); p = 0.043]. Similar effects were seen in the cancellous and endocortical envelopes. This pilot study shows a decrease of volumetric BMD and bone formation rate after high-dose radiation therapy. Further studies with larger cohorts and other endpoints are needed to get more insight into the effect of radiation on bone. Level of evidence: IV.

The effects of organic food on human health: a systematic review and meta-analysis of population-based studies.

Although the nutritional composition of organic food has been thoroughly researched, there is a dearth of published data relating to its impact on human health. This systematic review aimed to examine the association between organic food intake and health effects, including changes in in vivo biomarkers, disease prevalence, and functional changes. PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched from inception through Nov 13, 2022. Both observational and interventional studies conducted in human populations were included, and association between level of organic food intake and each outcome was quantified as "no association," "inconsistent," "beneficial correlation/harmful correlation," or "insufficient". For outcomes with sufficient data reported by at least 3 studies, meta-analyses were conducted, using random-effects models to calculate standardized mean differences. Based on the included 23 observational and 27 interventional studies, the association between levels of organic food intake and (i) pesticide exposure biomarker was assessed as "beneficial correlation," (ii) toxic metals and carotenoids in the plasma was assessed as "no association," (iii) fatty acids in human milk was assessed as "insufficient," (iv) phenolics was assessed as "beneficial", and serum parameters and antioxidant status was assessed as "inconsistent". For diseases and functional changes, there was an overall "beneficial" association with organic food intake, and there were similar findings for obesity and body mass index. However, evidence for association of organic food intake with other single diseases was assessed as "insufficient" due to the limited number and extent of studies. Organic food intake was found to have a beneficial impact in terms of reducing pesticide exposure, and the general effect on disease and functional changes (body mass index, male sperm quality) was appreciable. More long-term studies are required, especially for single diseases. PROSPERO registration no. CRD42022350175.

Decarbonization Pathways, Strategies, and Use Cases to Achieve Net-Zero CO2 Emissions in the Steelmaking Industry

The steelmaking industry is responsible for 7% of global CO2 emissions, making decarbonization a significant challenge. This review provides a comprehensive analysis of current steel-production processes, assessing their environmental impact in terms of CO2 emissions at a global level. Limitations of the current pathways are outlined by using objective criteria and a detailed review of the relevant literature. Decarbonization strategies are rigorously evaluated across various scenarios, emphasizing technology feasibility. Focusing on three pivotal areas—scrap utilization, hydrogen integration, and electricity consumption—in-depth assessments are provided, backed by notable contributions from both industrial and scientific fields. The intricate interplay of technical, economic, and regulatory considerations substantially affects CO2 emissions, particularly considering the EU Emissions Trading System. Leading steel producers have established challenging targets for achieving carbon neutrality, requiring a thorough evaluation of industry practices. This paper emphasizes tactics to be employed within short-, medium-, and long-term periods. This article explores two distinct case studies: One involves a hot rolling mill that utilizes advanced energy techniques and uses H2 for the reheating furnace, resulting in a reduction of 229 kt CO2-eq per year. The second case examines DRI production incorporating H2 and achieves over 90% CO2 reduction per ton of DRI.

Old for young: Cross-national examination of intergenerational political solidarity

Socioecological crises, such as the climate crisis, place a heavy burden on young and future generations. However, these generations have less influence on political and economic decisions. Older generations will be less affected by most socioecological crises but have a greater impact in terms of contribution and resolution. Therefore, young and future generations depend on older generations to act in solidarity. In a preregistered online survey study, we examined the political solidarity of older adults with young people in three countries (US, N = 399; Germany, N = 401; and Brazil, N = 403). Results show that affinity with young people and legacy motivation directly explained intergenerational political solidarity in all three countries. In the US and Brazil, quantity and quality of intergenerational contact with young people indirectly explained political solidarity through affinity. These findings suggest that increasing the closeness between generations may be a promising lever for intergenerational solidarity.

Repeated mild traumatic brain injury causes sex-specific increases in cell proliferation and inflammation in juvenile rats

Childhood represents a period of significant growth and maturation for the brain, and is also associated with a heightened risk for mild traumatic brain injuries (mTBI). There is also concern that repeated-mTBI (r-mTBI) may have a long-term impact on developmental trajectories. Using an awake closed head injury (ACHI) model, that uses rapid head acceleration to induce a mTBI, we investigated the acute effects of repeated-mTBI (r-mTBI) on neurological function and cellular proliferation in juvenile male and female Long-Evans rats. We found that r-mTBI did not lead to cumulative neurological deficits with the model. R-mTBI animals exhibited an increase in BrdU + (bromodeoxyuridine positive) cells in the dentate gyrus (DG), and that this increase was more robust in male animals. This increase was not sustained, and cell proliferation returning to normal by PID3. A greater increase in BrdU + cells was observed in the dorsal DG in both male and female r-mTBI animals at PID1. Using Ki-67 expression as an endogenous marker of cellular proliferation, a robust proliferative response following r-mTBI was observed in male animals at PID1 that persisted until PID3, and was not constrained to the DG alone. Triple labeling experiments (Iba1+, GFAP+, Brdu+) revealed that a high proportion of these proliferating cells were microglia/macrophages, indicating there was a heightened inflammatory response. Overall, these findings suggest that rapid head acceleration with the ACHI model produces an mTBI, but that the acute neurological deficits do not increase in severity with repeated administration. R-mTBI transiently increases cellular proliferation in the hippocampus, particularly in male animals, and the pattern of cell proliferation suggests that this represents a neuroinflammatory response that is focused around the mid-brain rather than peripheral cortical regions. These results add to growing literature indicating sex differences in proliferative and inflammatory responses between females and males. Targeting proliferation as a therapeutic avenue may help reduce the short term impact of r-mTBI, but there may be sex-specific considerations.

First Polyphasic Study of Cheffia Reservoir (Algeria) Cyanobacteria Isolates Reveals Toxic Picocyanobacteria Genotype.

Monitoring water supply requires, among other quality indicators, the identification of the cyanobacteria community and taking into account their potential impact in terms of water quality. In this work, cyanobacteria strains were isolated from the Cheffia Reservoir and identified based on morphological features, the 16S rRNA gene, phylogenetic analysis, and toxin production by polymerase chain reaction PCR screening of the genes involved in the biosynthesis of cyanotoxins (mcyA, mcyE, sxtA, sxtG, sxtI, cyrJ, and anaC). Thirteen strains representing six different genera: Aphanothece, Microcystis, Geitlerinema, Lyngbya, Microcoleus, and Pseudanabaena were obtained. The results demonstrated the importance of morphological features in determining the genus or the species when incongruence between the morphological and phylogenetic analysis occurs and only the utility of the 16S rRNA gene in determining higher taxonomic levels. The phylogenetic analysis confirmed the polyphyly of cyanobacteria for the Microcystis and Oscillatoriales genera. Unexpectedly, Aphanothece sp. CR 11 had the genetic potential to produce microcystins. Our study gives new insight into species with picoplanktonic (or small) cell size and potentially toxic genotypes in this ecosystem. Thus, conventional water treatment methods in this ecosystem have to be adapted, indicating the requirement for pre-treatment methods that can effectively eliminate picocyanobacteria while preserving cell integrity to prevent toxin release.

Multiscale numerical modeling of a complete spray evolution including breakup of liquid jet injection in gaseous cross flow

A direct coupling of the Volume of Fluid method (VOF) and the Lagrangian Particle Tracking (LPT) technique within a Large Eddy Simulation (LES) framework is revisited and assessed by numerically investigating a liquid jet injection into a cross-flowing air (JICF). To close the subgrid scale (SGS) terms appropriate SGS models are considered. In particular, an interfacial SGS term is included into the VOF scalar transport equation in order to achieve a suitable LES and to describe properly the liquid column and the break-up processes (primary and secondary). The dilute spray region including the droplets resulting from the secondary breakup is solved using the LPT approach. Since the latter allows the cell size to be multiple times larger than the droplet diameter, this reduces the computational expenses significantly making it possible to handle the simulation of the whole spray evolution including the complete liquid atomization without complex tunable atomization models. For this purpose, two operating conditions of a JICF existing in the literature are considered. The achieved results are first presented in terms of mesh sensitivity, required computational costs and impact of the interfacial SGS term. Next, comparisons between pure VOF/LES and VOF/LPT/LES for both qualitative features and quantitative properties are provided and discussed. In overall, a good agreement with experiments for the quantitative properties is reported. It is especially found that both the Rosin–Rammler and Gaussian distributions offer nearly a more accurate fit to the particle size distribution except for the range from 0 to 10 μm. Together with the detailed characteristics of vortices evolving and an extended breakup regime map, the spray characteristics including the spray structure are well captured. Finally, even though the interfacial SGS term has an evident influence on the jet and atomization dynamics, its impact on quantitative properties is not so prominent under these operating conditions.

The burden of the knowledge-to-action gap in acute appendicitis

BackgroundThe burden of emergency general surgery (EGS) is higher compared to elective surgery. Acute appendicitis (AA) is one of the most frequent diseases and its management is dictated by published international clinical practice guidelines (CPG). Adherence to CPG has been reported as heterogeneous. Barriers to clinical implementation were not studied. This study explored barriers to adherence to CPG and the clinico-economic impact of poor compliance.MethodsData were extracted from the three-year data lock of the REsiDENT-1 registry, a prospective resident-led multicenter trial. We identified 7 items from CPG published from the European Association of Endoscopic Surgery (EAES) and the World Society of Emergency Surgery (WSES). We applied our classification proposal and used a five-point Likert scale (Ls) to assess laparoscopic appendectomy (LA) difficulty. Descriptive analyses were performed to explore compliance and group comparisons to assess the impact on outcomes and related costs. We ran logistic regressions to identify barriers and facilitators to implementation of CPG.ResultsFrom 2019 to 2022, 653 LA were included from 24 centers. 69 residents performed and coordinated data collection. We identified low compliance with recommendations on peritoneal irrigation (PI) (25.73%), abdominal drains (AD) (34.68%), and antibiotic stewardship (34.17%).Poor compliance on PI and AD was associated to higher infectious complications in uncomplicated AA. Hospitalizations were significantly longer in non-compliance except for PI in uncomplicated AA, and costs significantly higher, exception made for antibiotic stewardship in complicated AA. The strongest barriers to CPG implementation were complicated AA and technically challenging LA for PI and AD. Longer operative times and the use of PI negatively affected antibiotic stewardship in uncomplicated AA. Compliance was higher in teaching hospitals and in emergency surgery units.ConclusionsWe confirmed low compliance with standardized items influenced by environmental factors and non-evidence-based practices in complex LA. Antibiotic stewardship is sub-optimal. Not following CPG may not influence clinical complications but has an impact in terms of logistics, costs and on the non-measurable magnitude of antibiotic resistance. Structured educational interventions and institutional bundles are required.

Sick leave length and the costs of operatively and conservatively treated distal radius fractures in the working age population: a retrospective cohort study

BackgroundAmong the working population, a transient loss of working ability due to distal radius fracture (DRF) has a societal impact in terms of sick leave. Non-operative cast immobilization is the most common treatment option for DRF. However, these fractures are increasingly treated operatively. This retrospective cohort study of patients aged 20–64 with DRF compares the effects of different treatment strategies on sick leave length and overall cost of treatment.MethodsMultivariable regression analysis was used with treatment modality as an exposure and sick leave length as an outcome. Sick leave data were obtained from a national register. Costs were evaluated by adding the direct cost of the treatment modality to the mean cost of sick leave per patient in different treatment groups.ResultsOf 614 working-age patients with a DRF who were treated at a tertiary hospital in Finland between January 2013 and December 2014, 521 were primarily treated non-operatively with cast immobilization and 93 were primarily operated. Of the primarily non-operatively treated patients, 48 were operated during follow-up. The mean follow-up was 5 years. The median time lost from work after DRF was 55 days (7.9 weeks), and the separated medians by treatment modality were 49 (7 weeks) and 70 days (10 weeks) for conservative and operative treatment, respectively. Multivariable linear regression analyses were performed for those patients who had sick leave (n = 292). Regression analysis also showed that operative treatment correlates with longer sick leave.ConclusionsOperative treatment of distal radius fracture led more often to longer time lost from work than conservative treatment. Moreover, due to longer sick leave and the costs of the operation itself, operative treatment is over two times more expensive than conservative treatment.Trial registrationretrospectively registered.

Setting Students up for Success

Acknowledging the importance of skill development in graduate programs, Western University in Canada developed an innovative master’s program in interdisciplinary medical sciences. The program aims to promote students’ academic, professional, and personal skills by engaging them in experiential and interdisciplinary learning that adopts an explicit and reflective approach in focusing on seven core skills: problem-solving, communication, leadership, critical reflection, working in diverse teams, project management, and decision making. This paper draws on the experiences and reflections of the inaugural cohort of students enrolled in the program to address the following research questions: 1) How does the MSc IMS program impact students’ skill development? and 2) How did students practise the seven core interdisciplinary skills outlined in the program? The study utilizes a mixed methods approach by collecting quantitative and qualitative data using pre- and post-online surveys administered to the students. The findings highlight the program's positive impact in terms of students’ reflection on their level of competence in the seven core skills, especially in complex problem-solving, oral and written communication skills, and critical reflection. Results also show that students specifically appreciated the contribution of experiential learning components of the program in advancing their skills. The paper emphasizes the importance of addressing students’ skill development in higher education in an explicit and intentional approach and engaging students in reflective practise on their skill development. Implications for the design and review of graduate programs are also discussed.

Impact of the 50 biggest pharma companies: a review of Environmental report aspiring to NetZero

Abstract Background Pharmaceutical companies have a considerable environmental impact in terms of waste disposal, CO2 emissions, plastic usage, and air pollution, water and energy consumption (including those related to transportation and refrigeration of drugs). According to data from 2019, pharmacological firms’ CO2 emissions are 13% greater than those of the car industry. To follow a greener path, pharmaceutical companies should primarily invest in sustainable production and supply, standard criteria, rewards programs, and staff training. This review aims to examine how pharmaceutical businesses incorporate environmental sustainability concerns into their operations, regulations, and communications. Methods We selected the top 50 pharmaceutical companies by revenue using the drugdiscoverytrends.com database. We collected the 2021 ESG report for each company, examining the following aspects: the inclusion of a ‘sustainability’ section or a downloadable sustainability report; the disclosure of the company production and carbon footprint; the existence of concrete measures to limit CO2 emissions, save water and energy, and reduce the effect of transportation. Data were analyzed through descriptive statistics to assess the sustainability of companies. Results Preliminary results indicate that each organization has a different level of importance for the topic of sustainability. Companies focused on CO2 production, few on other areas such as water needs or impact on biodiversity. Logistics correspond to the most impactful carbon footprint. Future forecasts and the path to NetZero emissions will also be emphasized, possibly comparing them with upcoming ESG 2022 reports. Conclusions The first results of our review show that the 50 biggest pharmaceutical companies have a different kind of interest towards environmental-friendly actions. Those with the highest revenues seem to be more careful towards the green issues, but the route to NetZero is still far to be achieved. Key messages • The environmental impact of pharmaceutical companies is greater than other industries. They must balance their business goals with environmental sustainability to reach NetZero as soon as possible. • The future goal of public health will be to monitor the environmental impact of drug production.

Assessment of Rheological Models Applied to Blood Flow in Human Thoracic Aorta.

The purpose of this study is to assess the importance of non-Newtonian rheological models on blood flow in the human thoracic aorta. The pulsatile flow in the aorta is simulated using the models of Casson, Quemada and Walburn-Schneck in addition to a case of fixed (Newtonian) viscosity. The impact of the four rheological models (using constant hematocrit) was assessed with respect to (i) magnitude and deviation of the viscosity relative to a reference value (the Newtonian case); (ii) wall shear stress (WSS) and its time derivative; (iii) common WSS-related indicators, OSI, TAWSS and RRT; (iv) relative volume and surface-based retrograde flow; and (v) the impact of rheological models on the transport of small particles in the thoracic aorta. The time-dependent flow in the thoracic aorta implies relatively large variations in the instantaneous WSS, due to variations in the instantaneous viscosity by as much as an order of magnitude. The largest effect was observed for low shear rates (tens s-1). The different viscosity models had a small impact in terms of time- and spaced-averaged quantities. The significance of the rheological models was clearly demonstrated in the instantaneous WSS, for the space-averaged WSS (about 10%) and the corresponding temporal derivative of WSS (up to 20%). The longer-term accumulated effect of the rheological model was observed for the transport of spherical particles of 2 mm and 2 mm in diameter (density of 1200 kg/m3). Large particles' total residence time in the brachiocephalic artery was 60% longer compared to the smaller particles. For the left common carotid artery, the opposite was observed: the smaller particles resided considerably longer than their larger counterparts. The dependence on the non-Newtonian properties of blood is mostly important at low shear regions (near walls, stagnation regions). Time- and space-averaging parameters of interest reduce the impact of the rheological model and may thereby lead to under-estimation of viscous effects. The rheological model affects the local WSS and its temporal derivative. In addition, the transport of small particles includes the accumulated effect of the blood rheological model as the several forces (e.g., drag, added mass and lift) acting on the particles are viscosity dependent. Mass transport is an essential factor for the development of pathologies in the arterial wall, implying that rheological models are important for assessing such risks.

Systematic exploration of a decade of publications on psychiatric genetics in Latin America.

Psychiatric disorders have a great impact in terms of mortality, morbidity, and disability across the lifespan. Considerable effort has been devoted to understanding their complex and heterogeneous genetic architecture, including diverse ancestry populations. Our aim was to review the psychiatric genetics research published with Latin American populations from 2010 to 2019, and classify it according to country of origin, type of analysis, source of funding, and other variables. We found that most publications came from Brazil, Mexico, and Colombia. Also, local funds are generally not large enough for genome-wide studies in Latin America, with the exception of Brazil and Mexico; larger studies are often done in collaboration with international partners, mostly funded by US agencies. In most of the larger studies, the participants are individuals of Latin American ancestry living in the United States, which limits the potential for exploring the complex gene-environment interaction. Family studies, traditionally strong in Latin America, represent about 30% of the total research publications. Scarce local resources for research in Latin America have probably been an important limitation for conducting bigger and more complex studies, contributing to the reduced representation of these populations in global psychiatric genetics studies. Increasing diversity must be a goal to improve generalizability and applicability in clinical settings.

Comparison of Techno-Economic Models for Upgrading PV System without Net-Metering Option and Long Term Impact on Energy Bills

This article presents a techno-economic analysis of upgrading a Photovoltaic (PV) power system at large. A comparative study has been carried out considering various technical and economic factors like per unit cost, annual load, energy demand growth, and PV panel efficiency, annual performance degradation of system, cost of electricity, payback period, initial capital expenditure, and rate of return in the form of saving in energy bills. The PV system is proposed to be upgraded from 1 MW to 2 MW at the National University of Sciences & Technology (NUST), Islamabad. The PV system is subject to be upgraded due to the growth rate of annual load and amount saved by PV contribution, which has been forecasted using data trends of the above-mentioned technical and economic factors. While considering these factors, four economic models have been evaluated and compared, which include Self-Built via Contractor with self-financing, Self-Built with bank financing, Power purchase agreement (PPA), also known as rental agreement and Built, Own, Operate & Transfer (BOOT) model. Merits and demerits of these models have been discussed, and the most feasible model has been proposed based on the mentioned key factors and long-term sustainable development goals (SDG) for affordable clean energy to contribute to climate action, i.e., adaptation of renewable energy resources (RER) and reduction of greenhouse gases (GHG).

Impact of different components of the Skyrme nucleon–nucleon effective interaction on the nuclear density distribution

We systematically investigate the impact of the different terms of the Skyrme energy density functional of the effective nucleon-nucleon interaction, and of its associated nuclear matter (NM) properties, on the density distributions of spherical nuclei. Twenty five Skyrme force parameterizations are examined simultaneously, covering a broad range of each characteristic parameter and NM property. The diffuseness and the neutron-skin thickness are found to be the most sensitive density quantities to the force parameterization. The diffuseness is indicated to decrease with increasing the central zero-range and the effective mass terms of the effective force, and the power σ of its density dependent term, as well as with the coefficient of the NM symmetry energy (asym) and its density slope (L) at saturation density, and the incompressibility (Ko). In contrast, the proton and neutron diffuseness tend to increase with increasing the spin–orbit force and the isoscalar effective nucleon-mass (m*), and to increases slightly with the density dependence parameters other than the power σ. Opposite impacts are pointed out for the different parts of the finite-range, and J2 tensor terms on the proton and neutron density. While the neutron-skin thickness tends to increase significantly upon increasing the central zero-range and spin–orbit force terms, asym, L, and Ko, and to increase slightly with the finite-range and J2 tensor terms, and σ, it decreases with the effective-mass term, the density-dependence exchange parameter, and with the indicated isoscalar effective mass. The proton and neutron radii exhibit decreasing behavior with the central zero-range and the spin–orbit terms, and with Ko, and m*. Increasing asym and L indicate slightly less (larger) proton (neutron) radius.