Evaluation Period Research Articles

Trends in mercury, lead and cadmium concentrations in 27 European streams and rivers: 2000–2020

Temporal trends for concentrations of mercury (Hg), lead (Pb) and cadmium (Cd) were evaluated from year 2000–2020 in 20 (Hg), 23 (Pb) and 11 (Cd) watercourses in remote forest catchments in Europe. Decreasing trends were observed in 15% (Hg), 39% (Pb) and 45% (Cd) of the watercourses during the period of evaluation. Decreasing trends were mainly observed between 2000 and 2005 for Hg and between 2000 and 2015 for Pb and Cd. For the last five years of the studied time period (2015–2020), more watercourses showed significant increasing, rather than decreasing Hg, Pb and Cd trends. This was interpreted as a legacy effect of metals still retained in catchment soils. The overall negative trends during the earlier part of the study period were likely driven by declining deposition of metals over Europe, especially for Pb and Cd. Other changes related to metal transport and chemistry may have contributed to the observed trends as well, including recovery from acidification and the ongoing browning of surface waters at northern latitudes. Here we found that organic carbon could explain the seasonal variation in Hg and Pb, but was not related the interannual trends. This study highlights the need for long-term monitoring and robust statistical methods that can detect multidirectional, long-term change in water chemistry.

Strategies to promote contraception use by female volunteers in Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Colombia trial.

Including women of childbearing age in a clinical trial makes it necessary to consider two factors from a bioethical perspective: first, the lack of knowledge about the potential teratogenic effects of an investigational product, and also, the principle of justice not to exclude any population from the benefits of research. The most common way to address this issue is by requiring volunteers to use contraceptives before, during, and a few weeks after the clinical trial. This work presents all the strategies used to promote contraception use and prevent pregnancy during the Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease (API ADAD) Colombia clinical trial. Two characteristics of this trial make it of special interest for closely monitoring contraception use. One is that the trial lasted more than 7 years, and the other is that participants could be carriers of the E280A PSEN1 mutation, leading to a mild cognitive impairment as early as their late 30s. An individual medical evaluation to select the contraception method that best fits the volunteer was carried out during the screening visit, remitting to the gynecologist when necessary. All non-surgical contraception methods were supplied by the sponsor. Staff were trained on contraception counseling, correctly dispensing contraceptive drugs to volunteers, and identifying, reporting, and following up on pregnancies. Two comprehensive educational campaigns on contraception use were performed, and the intervention included all volunteers. In addition, volunteers were asked on an annual survey to evaluate the dispensing procedure. Finally, the effectiveness of these strategies was retrospectively evaluated, comparing by extrapolation the number of pregnancies presented throughout the trial with the General Fertility Rate in Colombia. A total of 159 female volunteers were recruited. All strategies were implemented as planned, even during the COVID-19 contingency. Ten pregnancies occurred during the evaluation period (2015-2021). Two were planned; the rest were associated with a potential therapeutic failure or incorrect use of contraceptive methods for a contraceptive failure of 0.49% per year. Sixty percent of pregnancies led to an abortion, either miscarriage or therapeutic abortion. However, there was not enough data to associate the pregnancy outcome with the administration of the investigational product. Finally, we observed a lower fertility rate in women participating in the trial compared to the Colombian population. The lower rates of contraceptive failure and the decrease in the incidence of pregnancies in women participating in the trial compared to the Colombian population across the 7 years of evaluation suggest that the strategies used in API ADAD Colombia were adequate and effective in addressing contraception use.

The Efficacy of Topical or Systemic Antibiotics as Adjuvants to Non-Surgical Periodontal Treatment in Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: Periodontitis and diabetes mellitus (DM) exhibit a bidirectional relationship and are globally significant systemic chronic conditions. The utilization of antibiotics alongside non-surgical periodontal treatment (NSPT) has been a subject of investigation in numerous clinical studies involving human subjects. Thus, the objective of this systematic review is to address the following question: "What is the efficacy of scaling and root planing (SRP) associated with antimicrobials in patients with type 2 DM and periodontitis?". Methods: A systematic review of the literature was conducted encompassing databases such as MEDLINE/PubMed, Scopus, and Web of Science up to July 2024. Additionally, alerts were configured to capture studies published from the initial search until manuscript submission. Randomized clinical trials assessing clinical periodontal parameters in DM patients undergoing SRP and receiving either topical or systemic antibiotics were compared against a control group (SRP only). Two investigators independently screened articles, extracted data, and evaluated their quality. The selection process, study characteristics, risk of bias, impact of antibiotics on clinical parameters, and certainty of evidence were elucidated in both textual and tabular formats. Meta-analysis was performed separately with forest plots generated for treatment modalities, period of evaluation, and type of antibiotics used. Results: Following the analysis of abstracts and full articles, a total of 30 randomized clinical trials were incorporated into this review, comprising 9 studies on the association of topical antibiotics and 21 studies on systemic antibiotic administration. The principal periodontal parameters assessed included probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BoP). Conclusions: Analysis of the results led to the conclusion that adjunctive periodontal treatment with either topical or systemic antibiotics confers subtle clinical benefits. Nevertheless, owing to the heightened emergence of resistant bacteria and potential side effects, the use of antibiotic therapy in periodontal treatment should be judiciously administered.

Influencer detection meets network autoregression — Influential regions in the bitcoin blockchain

Known as an active global virtual money network, the Bitcoin blockchain, with millions of accounts, has played a continually increasingly important role in fund transition, digital payment, and hedging. We propose a method to Detect Influencers in Network AutoRegressive models (DINAR) via sparse-group regularization to detect regions influencing others across borders. For a granular analysis, we analyse whether the transaction size plays a role in the dynamics of the cross-border transactions in the network. With two-layer sparsity, DINAR enables discovering (1) the active regions with influential impact on the global digital money network and (2) whether changes in the size of the transaction affect the dynamic evolution of Bitcoin transactions. In the analysis of real data of the Bitcoin blockchain from Feb 2012 to December 2021, we find that influence from certain regions is linked to the economic need to use BTC, such as to circumvent sanctions, avoid high inflation, and to carry out transactions through off-shore markets. The effects are robust to different groupings, evaluation periods, and choices of regularization parameters.

Impact of Photobiomodulation and Melatonin on Periodontal Healing of Periodontitis in Immunosuppressed Rats.

Introduction: Periodontitis is an inflammatory disease due to bacterial origin; it has a chronic course and progresses by immunosuppressive therapy. However, adjuvant therapies such as photobiomodulation (PBM) and melatonin can reduce the severity of the inflammation and inhibit the progression of periodontitis. Therefore, the present study evaluated the effects of PBM (PBM) and melatonin, as adjuvant therapies, on periodontal healing in immunosuppressed rats with periodontitis. Methods: Random allocation was performed on 36 albino Wistar rats, divided into the following groups: control, periodontitis, immunosuppressant only, immunosuppressant+PBM, immunosuppressant+melatonin, and immunosuppressant+melatonin+PBM. Periodontitis caused by ligature in all groups, except for the control group. Subcutaneous administration of dexamethasone was performed in the immunosuppressant groups for immunosuppression. All the groups except the control group received scaling and root planning (SRP). Each group was subdivided into three equal subgroups according to the evaluation period: (A), one week, (B) two weeks (C), 4 weeks. Histological examination was done with haematoxylin & eosin and Masson's Trichrome for inflammation and periodontal healing. Statistical Analysis of the data was done by using the chi-square test. The significance level was set at P≤0.05. Results: Regarding the inflammatory response and periodontal healing, histological examination revealed statistically significant difference in all treated groups in comparison with the control untreated immunosuppressed group (P<0.001). The combined application of melatonin and PBM resulted in a best histological response presented by lower inflammatory response and better periodontal healing, when compared with all other treated groups (P<0.001). Conclusion: After considering the circumstances of this research, the combination of melatonin and PBM by a 650 nm diode laser with output power of 100 mw for one minute for three sessions appeared to be a beneficial adjunct in periodontal healing in immunosuppressed rats with periodontitis.

Evaluation of Pepper (Capsicum spp.) Germplasm Collection for Bacterial Wilt (Ralstonia solanacearum) Resistance

This study was conducted to identify resistant pepper accessions against the destructive disease bacterial wilt (BW) caused by Ralstonia solanacearum. A total of 338 pepper (Capsicum species) germplasms collected from different countries and deposited in the National Agrobiodiversity Genebank, Rural Development Administration (RDA), Republic of Korea, were evaluated. The evaluated accessions comprise samples from five distinct species: Capsicum annuum (213), Capsicum baccatum (47), Capsicum chinense (45), Capsicum frutescens (31), and Capsicum chacoense (2). Disease severity scores were recorded over four consecutive weeks and showed an increase in severity from initial inoculation to the end of the evaluation period. A strong correlation was observed between week 1 and 2, as well as between week 3 and 4. Ten resistant pepper accessions were identified. All selected accessions consistently exhibited low disease scores ranging from 0 to 1 throughout the observation period. These accessions belong to C. chinense (2), C. annuum (6), C. chacoense (1), and C. frutescens (1). Accessions such as IT236738 (C. chinense) and IT283498 (C. chinense) were demonstrated to have high resistance, showing no symptoms over all four weeks. Other accessions belonging to C. annuum (IT247232 and IT236340) and C. chacoense (IT158713) maintained a disease score of 0 (no symptoms) for the first three consecutive weeks; however, they developed symptoms with a score of 1 in the fourth week. Other important characteristics of the resistant materials were evaluated, including carotenoids and fruit characteristics. These accessions have important traits beyond resistance to the destructive pepper disease. They will serve as promising resources for breeding resistant pepper varieties against BW to enhance productivity.

Personalized insulin dosing using reinforcement learning for high-fat meals and aerobic exercises in type 1 diabetes: a proof-of-concept trial

In type 1 diabetes, high-fat meals require more insulin to prevent hyperglycemia while meals followed by aerobic exercises require less insulin to prevent hypoglycemia, but the adjustments needed vary between individuals. We propose a decision support system with reinforcement learning to personalize insulin doses for high-fat meals and postprandial aerobic exercises. We test this system in a single-arm 16-week study in 15 adults on multiple daily injections therapy (NCT05041621). The primary objective of this study is to assess the feasibility of the novel learning algorithm. This study looks at glucose outcomes and patient reported outcomes. The postprandial incremental area under the glucose curve is improved from the baseline to the evaluation period for high-fat meals (378 ± 222 vs 38 ± 223 mmol/L/min, p = 0.03) and meals followed by exercises (−395 ± 192 vs 132 ± 181 mmol/L/min, p = 0.007). The postprandial time spent below 3.9 mmol/L is reduced after high-fat meals (5.3 ± 1.6 vs 1.8 ± 1.5%, p = 0.003) and meals followed by exercises (5.3 ± 1.2 vs 1.4 ± 1.1%, p = 0.003). Our study shows the feasibility of automatically personalizing insulin doses for high-fat meals and postprandial exercises. Randomized controlled trials are warranted.

The PRIME-NL study: evaluating a complex healthcare intervention for people with Parkinson’s disease in a dynamic environment

BackgroundAn innovative, integrative care model for people with Parkinson (PRIME Parkinson) has gradually been implemented in a selected region of the Netherlands since 2021. A prospective evaluation of this model (PRIME-NL study) was initiated in parallel, spanning the year prior to implementation (baseline) and the implementation period. Following publication of the original study protocol, the COVID-19 crisis delayed implementation of the full PRIME Parkinson care model by two years and hampered the recruitment of study participants.ObjectiveTo describe which methodological adjustments were made to the study protocol because of these developments.MethodsWe compare various outcomes between a region where PRIME Parkinson care was implemented (innovation region) versus the rest of the Netherlands (usual care region). We use healthcare claims data of virtually all people with Parkinson in the Netherlands and annual questionnaires in a representative subsample of 984 people with Parkinson, 566 caregivers and 192 healthcare professionals. Four major methodological adjustments had to be made since publication of the original protocol. First, we extended the evaluation period by two years. Second, we incorporated annual process measures of the stage of implementation of the new care model. Third, we introduced a real-time iterative feedback loop of interim results to relevant stakeholders. Fourth, we updated the statistical analysis plan.DiscussionThis manuscript provides transparency in how the design and analyses of the evaluation study had to be adapted to control for external influences in a dynamic environment, including eruption of the COVID-19 crisis. Our solutions could serve as a template for evaluating other complex healthcare interventions in a dynamic environment.

Formative qualitative evaluation of an improvement programme delivered in an English hospital trust to reduce harm from pressure ulcers

BackgroundPressure ulcers (PUs) are a leading cause of preventable harm globally and can cause patients significant pain, infection and, in rare incidents, death. There is a strong evidence base for...

Antisense Oligonucleotide as a New Technology Application for CsLOB1 Gene Silencing Aiming at Citrus Canker Resistance.

Citrus canker disease, caused by Xanthomonas citri subsp. citri, poses a significant threat to global citrus production. The control of the disease in the field relies mainly on the use of conventional tools such as copper compounds, which are harmful to the environment and could lead to bacterial resistance. This scenario stresses the need for new and sustainable technologies to control phytopathogens, representing a key challenge in developing studies that translate basic into applied knowledge. During infection, X. citri subsp. citri secretes a transcriptional activator-like effector that enters the nucleus of plant cells, activating the expression of the canker susceptibility gene LATERAL ORGAN BOUNDARIES 1 (LOB1). In this study, we explored the use of antisense oligonucleotides (ASOs) with phosphorothioate modifications to transiently inhibit the gene expression of CsLOB1 in Citrus sinensis. We designed and validated three potential ASO sequences, which led to a significant reduction in disease symptoms compared with the control. The selected ASO3-CsLOB1 significantly decreased the expression level of CsLOB1 when delivered through two distinct delivery methods, and the reduction of the symptoms ranged from approximately 15 to 83%. Notably, plants treated with ASO3 did not exhibit an increase in symptom development over the evaluation period. This study highlights the efficacy of ASO technology, based on short oligonucleotide chemically modified sequences, as a promising tool for controlling phytopathogens without the need for genetic transformation or plant regeneration. Our results demonstrate the potential of ASOs as a biotechnological tool for the management of citrus canker disease.

Performance analysis and degradation mechanism of acrylamide co-polymer as rheology and filtrate reducers in different salt aqueous-based drilling mud systems at high-temperature conditions

To maintain performance of an aqueous-based drilling muds (ABDMs), it was imperative to understand the decay mechanism of the incorporated synthetic polymers, when exposed to the elevated temperatures. The understanding of the decay mechanism could provide a polymer replenishment strategy for the fluid to retain a specific rheology and filtrate control performance. In this context, thermal-degradation of various acrylamide co-polymers was investigated in different monovalent brines. The acrylamide co-polymers were custom synthesized, and their molecular weight and % sulfonic substitution was verified using the capillary viscometer and nuclear magnetic resonance spectroscopy techniques respectively. The co-polymer thermal degradation mechanism (i.e., polymer hydrolysis) in various monovalent brines (KCl, NaCl and NaBr) was quantified by novel titration for temperature range {121 °C, 177 °C}. The degradation response of the co-polymers was then correlated with their rheology and HPHT (high-pressure-high-temperature) filtrate performance; for instance, the titration studies showed that co-polymer degradation was 12–15% and 44–47% after sixteen hours aging at 121 °C and 177 °C respectively; correspondingly the co-polymer performance in ABDM, exhibited HPHT filtrate of 12–18 mL and 38–40 mL at those respective temperatures after sixteen hours of aging. The quantified understanding of the co-polymer thermal degradation was used to device a new approach for co-polymer replenishment strategy; it was illustrated that a 7% replenishment of the co-polymer for every eight hours, at 121 °C, enabled sustained HPHT filtrate of 12–18 mL for the studied evaluation period of thirty-two hours. The replenishment approach presented in the study would provide a valuable tool for drilling automation to ensure sustained fluid performance.

Long-Term Safety of a Four-Factor Prothrombin Complex Concentrate (Kcentra®/Beriplex® P/N): An Updated Pharmacovigilance Review.

Four-factor prothrombin complex concentrate (4F-PCC) is recommended for vitamin K antagonist reversal in patients with major bleeding or in need of surgery. The most important risk associated with the use of 4F-PCC is the occurrence of thromboembolic events (TEEs). In this review, we aim to evaluate the safety profile of a 4F-PCC (Kcentra®/Beriplex® P/N; CSL Behring, Marburg, Germany) by reviewing pharmacovigilance data. A retrospective analysis of postmarketing pharmacovigilance data of Kcentra®/Beriplex® P/N from February 1996 to April 2022 was performed and complemented by a review of clinical studies published between January 2012 and April 2022. A total of 2,321,443 standard infusions of Kcentra®/Beriplex® P/N were administered during the evaluation period. Adverse drug reactions (ADRs) were reported in 614 cases (∼1 per 3,781 standard infusions) and 233 of these cases (37.9%) experienced suspected TEEs related to 4F-PCC (∼1 per 9,963 standard infusions); most of these cases had pre-existing or concomitant conditions likely to be significant risk factors for thrombosis. TEE rates were similar when 4F-PCC was used on-label or off-label for direct oral anticoagulant-associated bleeding. Thirty-six cases (5.9%) reported hypersensitivity type reactions (∼1 per 64,485 standard infusions). No confirmed case of viral transmission related to 4F-PCC use was reported. The published literature also revealed a favorable safety profile of 4F-PCC. Analysis of postmarketing pharmacovigilance safety reports demonstrated that treatment with 4F-PCC was associated with few ADRs and a low rate of TEEs across multiple indications and settings, thus confirming a positive safety profile of 4F-PCC.

5-Year clinical performance of ceramic onlay and overlay restorations luted with light-cured composite resin

ObjectivesThis prospective clinical trial evaluated the clinical performance of ceramic partial coverage indirect adhesive restorations (PCIARs) in posterior teeth luted with a light-cured composite resin. MethodsFrom April 2016 to January 2017, a total of 60 patients (27 males, 33 females; mean age: 42.2 ± 10.86 years old) received 83 glass-ceramic PCIARs (26 onlay, 57 overlay) made of IPS Emax CAD (Ivoclar Vivadent). All restorations were luted with a light-cured composite resin (Filtek Z250, 3 M ESPE) by two operators. Two independent calibrated examiners blinded to the operators performing the treatment evaluated the restorations at baseline, 1-year, and 5-year following FDI World Dental Federation criteria including esthetic, functional, and biological properties. Data were analyzed with the Friedman test and the Wilcoxon sign test (p < 0.05). ResultsNone of the restorations failed due to fracture or retention loss. One restoration was clinically unsatisfactory because of secondary caries. Marginal staining (p:0.000), marginal adaptation (p:0.018) showed significant differences between 1-year and 5-year recall. ConclusionsThe PCIARs demonstrated excellent clinical performance at 1-year period. The degradation parameters appeared as minor staining and minor irregularities after 5-year, without any affect on the clinical performance. Clinical SignificanceOur findings provide evidence that the clinical performance of PCIARs luted with a light-cured composite resin was clinically acceptable after a five-year evaluation period. Due to secondary caries, only one restoration was considered clinically unsatisfactory. ClinicalTrials registration number: NCT04838483

Comparative Evaluation of the Marginal Fit and Internal Adaptation of Polymethyl Methacrylate Interim Crowns Fabricated using two different techniques- “Conventional” and “CAD-CAM Milling”: An In Vitro Study

Introduction Interim crowns provide valuable functional and esthetic information of the final outcome during the evaluation period and act as the blueprint for the design of definitive prostheses. The fabrication technique and material used are the key factors involved in the success of the prosthesis. However, marginal fit and internal adaptation of Polymethyl Methacrylate (PMMA) interim crowns fabricated using conventional and computer aided designing-computer aided machining (CAD-CAM) PMMA milling have not been well investigated. The inter-group statistical comparison of means of normally distributed continuous variables is done using independent sample t test. Material and Methods Typodont (Nissin, Japan) of the maxillary central incisor was scanned (Ceramill Map 600+, Amann Girrbach AG) and 3D printed (Form 4, Formlabs) to create the master die used in the study, while a Typodont of a prepared maxillary central incisor was scanned using a digital scanner (Ceramill Map 600+, Amann Girrbach AG) and a .STL file obtained was modified using Exocad software for designing the study models. Three equidistant points A, B and C passing from the center of the incisal edge to the root of the typodont were indented labially and A` B` and C` were indented palatally in the same plane using Exocad software for symmetrical sectioning while checking for marginal fit and internal adaptation. 50 3D printed (Form 4, Formlabs India) models of the prepared tooth were printed and 25 interim crowns were fabricated using Polymethyl Methacrylate (DPI Tooth moulding material, DPI India) by conventional and 25 interim crowns were fabricated using CAD-CAM PMMA (Ceramill a-temp, Amann Girrbach AG). They were then luted (Han Temp Cement eugenol free, NE Korea) to respective models and viewed under a stereomicroscope (Ziess) for marginal fit at 2 specific points and internal adaptation at 4 specific points. Results The mean SD of marginal fit measurements at buccal and site in Group A (conventional technique) and Group B (CAD-CAM milling) was 95.32 ± 7.78 µm and 66.92 ± 14.59 µm respectively. At lingual site in Group A and Group B was 94.84 ± 7.97 µm and 66.80 ± 10.93 µm respectively. The mean marginal fit measurement at lingual site is significantly higher in Group A compared to Group B (P-value%3C0.05). The mean SD of internal fit measurements at upper 1 site in Group A and Group B was 335.19 ± 94.70 µm and 226.76 ± 89.68 µm respectively. At upper 2 site in Group A and Group B was 368.88 ± 120.25 µm and 240.85 ± 93.72 µm respectively. At lower 1 site in Group A and Group B was 313.52 ± 99.92 µm and 262.49 ± 94.33 µm respectively. At lower 2 site in Group A and Group B was 367.93 ± 107.36 µm and 264.52 ± 86.97 µm respectively. The mean internal fit measurement is significantly higher in Group A compared to Group B (P-value%3C0.05). Conclusion The interim crowns fabricated using the conventional technique displayed a less favourable marginal fit and internal adaptation when compared to CAD-CAM fabricated interim crowns. Key Words CAD-CAM, Interim crowns, Marginal fit and internal adaptation

Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone followed by brentuximab vedotin consolidation in CD30-positive peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 study

CD30 expression is universal in anaplastic large-cell lymphoma and is expressed in some other peripheral T-cell lymphoma subtypes. Incorporation of brentuximab vedotin into initial therapy for people with CD30-positive peripheral T-cell lymphomas prolonged progression-free survival, but there is room for improvement, especially for people with non-anaplastic large-cell lymphoma subtypes. We conducted a multicentre, international, single-arm, phase 2 trial to evaluate the safety and activity of CHEP-BV (cyclophosphamide, doxorubicin, prednisone, brentuximab vedotin, and etoposide) followed by brentuximab vedotin consolidation in patients with CD30-expressing peripheral T-cell lymphomas across five academic centres in the USA and Canada. Adults aged 18 years or older with newly diagnosed, untreated CD30-positive peripheral T-cell lymphomas, Eastern Cooperative Oncology Group score of 0-2, and adequate organ function were eligible to receive six planned cycles of CHEP-BV (ie, 1·8 mg/kg brentuximab vedotin intravenously on day 1, cyclophosphamide 750 mg/m2 intravenously on day 1, doxorubicin 50 mg/m2 intravenously on day 1, etoposide 100 mg/m2 daily intravenously on days 1-3, and prednisone 100 mg daily orally on days 1-5) with prophylactic G-CSF. Patients who responded to the treatment could receive brentuximab vedotin consolidation for up to ten additional cycles either after autologous haematopoietic stem-cell transplantation (HSCT) or directly after CHEP-BV. The primary endpoints were unacceptable toxicity during a 3-plus-3 safety lead-in in participants who received study treatment and completed the safety evaluation period (to confirm the recommended phase 2 dose of brentuximab vedotin in CHEP-BV) and the complete response rate after CHEP-BV induction therapy in participants who received study treatment and had response evaluation. The study was registered at ClinicalTrials.gov (NCT03113500), and this cohort completed the trial. The trial is ongoing with the enrolment of a new cohort. 54 patients were screened for eligibility and 48 were eligible for the study. The participants (18 [38%] women and 30 [63%] men; 34 [71%] White, four [8%] Black, five [10%] Asian, ten [21%] Hispanic, and 37 [77%] non-Hispanic people) were recruited and enrolled between Dec 4, 2017, and June 14, 2021, and followed up until Aug 25, 2023, when the database was locked for analysis. 48 participants were evaluable for toxicity, and 47 were evaluable for response (one participant died from COVID-19 before response assessment). During the safety lead-in, one of six participants had an unacceptable toxicity (ie, platelet count <10 000 per mm3 in a participant with extensive bone marrow involvement), and the proposed phase 2 dose of 1·8 mg/kg brentuximab vedotin in CHEP-BV was confirmed. At completion of CHEP-BV, 37 of 47 participants had complete response, yielding a complete response rate of 79% (95% CI 64-89). The most common CHEP-BV-related toxicities of grade 3 or higher were neutropenia (14 [29%] of 48), leukopenia (11 [23%]), anaemia (ten [21%]), febrile neutropenia (ten [21%]), lymphopenia (nine [19%]), and thrombocytopenia (nine [19%]). There were no treatment-related deaths. In patients with mostly CD30-expressing peripheral T-cell lymphomas other than non-anaplastic large-cell lymphoma, CHEP-BV (with or without autologous HSCT) followed by brentuximab vedotin consolidation was safe and active. SeaGen, Leukemia and Lymphoma Society, Lymphoma Research Foundation, and the National Cancer Institute of the National Institutes of Health.

Effects of conservation agriculture technologies on soil macrofauna community attributes in rainfed agriculture system

AbstractInappropriate rainfed crop management, especially wrong tillage and crop residue management, led to reduce the diversity of soil biological quality, especially soil macrofauna community, in semiarid region. This study was conducted to investigate the effect of 5 year conservation agriculture operation techniques on the quality and the diversity indices of soil macrofauna community in the rainfed lands in the west of Iran. This experiment was carried out in the statistical format of split‐split plots based on a randomized completely block design with three replications. The main treatments include control or conventional tillage, compound tillage, chisel tillage, and direct cultivation (no tillage) with three sub‐treatments of plant residues (no residues, one‐third, and two‐thirds of plant residues) in rainfed wheat (Triticum aestivum) rotation with rainfed chickpea (Cicer arietinum). Changes in soil biological quality indicators, such as soil microbial respiration were measured. Also, the indicators related to the population of soil macrofauna, including biodiversity index, uniformity index, and species richness, were measured and the effect of treatments on the measured indicators were compared with the classical statistical method of analysis of variance and Duncan's mean comparison test. The results showed that conservation agricultural treatments, including no‐tillage treatment, have led to significant increase of 19% and 15% of macrofauna biodiversity index in wheat and chickpea, respectively. Also, keeping one‐third of the wheat residues has led to an 18% increase in the biodiversity index of the soil macrofauna during the evaluation period. Biodiversity index and taxonomic richness of soil macrofauna were generally higher in the years of wheat than chickpea, and on the contrary, the species uniformity index of soil macrofauna biological community was higher in chickpea than wheat.

Gaussian Process Regression Based Silver Price Forecasts

A significant number of market participants have placed a high level of importance on price estimates for the primary metal commodities for a considerable amount of time. To tackle the problem, we investigate the daily reported price of silver in our study. The sample that is being analyzed spans a period of 13 years, starting on April 20, 2011, and ending on April 19, 2024. The price series which is being investigated has important implications for the commercial world. Specifically, when it comes to this unique circumstance, Gaussian process regression models are developed utilizing cross-validation strategies and Bayesian optimization procedures. The forecasting of prices is therefore accomplished via the use of the methods that are developed as a result of the situation. For the out-of-sample evaluation period that extends from October 5, 2021 to April 19, 2024, our empirical forecasting approach yields price estimates deemed reasonably accurate. The relative root mean square error reached for the silver price is 0.2257%, with the corresponding root mean square error of 0.0515, mean absolute error of 0.0389, and correlation coefficient of 99.967%. Due to the availability of models that forecast prices, investors and governments are supplied with the information they need to make educated judgments on the silver market by providing them with the knowledge they require. The framework of the Gaussian process regression with Bayesian optimizations demonstrates its good potential for modeling and forecasting sophisticated commodity price series for market participants.

Early interventions with parental participation and their implications on the neurodevelopment of premature children: a systematic review and meta-analysis.

The occurrence of preterm birth is correlated with the potential emergence of disabilities in children. Early intervention programs are designed to promote better developmental outcomes. These interventions employ family-centered methodologies, wherein parents are instructed to facilitate neurodevelopment, thereby promoting heightened involvement of the child in their daily activities. The objective of this investigation was to evaluate the efficacy of early family-based interventions on motor, cognitive, and language development. A systematic review and meta-analysis was conducted utilizing the databases PubMed, Medline, PEDro, Scopus, CINAHL Complete, SciELO, and Open Grey. The search terms utilized included NDT (neuro-developmental treatment), Bobath, neurodevelopmental therapy, parents administered, family administered, physical therapy modalities, early intervention (educational), early intervention, premature infant, preterm, and premature. Randomized clinical trials and observational studies written in English or Spanish were taken into consideration. The initial search resulted in 420 articles. After removing duplicates and applying the selection criteria, 12 articles were selected for the systematic review and 5 articles were selected for the meta-analysis. The meta-analysis revealed a significant association between early intervention and enhanced cognitive function (p = 0.01) in this study. Additionally, the meta-analysis indicated improvements resulting from early family-based intervention (p = 0.02) in motor function. Early motor interventions that emphasize parent involvement and education in neurodevelopment show significant outcomes in motor and cognitive areas at 2 years of age in very premature or extremely premature infants. However, inconclusive effects have been found in the language area, which is the least studied domain. Due to the methodological heterogeneity observed, further research is needed to establish conclusive decisions regarding the administration of these interventions and the determination of key evaluation periods.

Application of topical 5-Fluorouracil to reduce the recurrence of odontogenic keratocyst: A prospective study with 2-year follow-up

ObjectivesThe purpose of this prospective study was to evaluate the effect of topical 5-Fluorouracil as an adjunct therapy in reducing the recurrence of odontogenic keratocyst. MethodsForty-eight patients with proven incisional biopsy as odontogenic keratocyst were included in this clinical study. The patients were divided into two equal groups, the test group patients were treated with 5-Fluorouracil cream after cyst enucleation. However, the control group patients were treated with cyst enucleation only. Recurrence (yes/no) was the primary outcome variable evaluated by clinical signs of inflammation, swelling, or pain within a 2-year follow-up. The pain was measured on a visual analogue scale, and swelling was measured pre-surgically using vertical and horizontal references, 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months. Computed tomography was performed pre-surgically and 24 hours post-surgically, at 12-month, and 24-month intervals to evaluate local bone density. The T-test was used to compare between two studied groups. ResultsPost-surgical follow-up showed uneventful wound healing in both groups with no clinical signs of recurrence or swelling, pain results demonstrated that patients have decreased records throughout the observation periods with no significant difference between both groups. Normal sensation was encountered in all patients except for one patient in the control group who showed no sensation (score 2). Post-surgical radiographic findings revealed a considerable shift in bone density in all patients of both groups at the site of excised lesions during the follow-up periods compared with immediate post-surgical radiographs. However, the test group patients demonstrated a significant increase of bone density between different evaluation periods (P = 0.001) than the control group. ConclusionConservative enucleation of odontogenic keratocyst combined with topical application of 5-Fluorouracil is an effective treatment with lower recurrence rates, less morbidity, and normal bone healing.

Screening Cover Crops for Utilization in Irrigated Vineyards: A Greenhouse Study on Species' Nitrogen Uptake and Carbon Sequestration Potential.

This study examines the potential of 23 plant species, comprising 10 legumes, 9 grasses, and 4 forbs, as cover crops to enhance carbon (C) sequestration and soil nitrogen (N) in vineyards. After a 120-day evaluation period, cover crop biomass was incorporated into the soil, and grapevine seedlings were planted in its place. Among the established cover crops, the C input potential ranged from 0.267 to 1.69 Mg ha-1, and the N input potential ranged from 12.3 to 114 kg ha-1. Legume species exhibited up to threefold greater shoot dry weight (SDW) compared to grass species. Ladino white clover, Dutch white clover, and Clover blend were superior in SDW, total dry weight (TDW), total C content, and total N content. Legumes exhibited slightly higher root dry weight (RDW) than grasses, with the exception of Fall rye leading at 15 g pot-1, followed by Ladino white clover and Dutch white clover at an average of 12 g pot-1. Legumes, particularly clover blend and Alsike clover, displayed high shoot N concentration at an average of 2.95%. Root N concentration in Legumes (Fabaceae) were significantly higher at 1.82% compared to other plant families at 0.89%, while their root C/N ratio was lower at 18.3, contrasting with others at 27.7, resulting in a faster turnover. Biomass production exhibited a negative relationship (R2 = 0.51) with soil residual NO3-. Fall rye, Winfred brassica, and buckwheat had the highest N utilization efficiency (NUtE) values (ava. 121 g g-1). Alsike clover, Ladino white clover, and clover blend showed the highest N uptake efficiency (NUpE) values (ava. 75%). The Readily Available N (RAN) Reliance Index (RANRI) is introduced as a novel indicator for quantifying the extent to which a plant relies on RAN for its total N requirement. The RANRI value represents the percentage of the plant's total N sourced from RAN, ranging from 11% for legumes to 86% for grasses. This implies a substantial influx of nitrogen through a pathway independent of RAN in legumes. Grape shoot N concentration positively correlated with soil NO3- (R2 = 0.31) and cover crop C/N ratio (R2 = 0.17) but negatively correlated with cover crop TDW (R2 = 0.31). This study highlights legume plants as more effective in C and N assimilation during establishment but cautions about potential soil mineral N depletion before reaching their full biological N fixation capacity.