Long-term Studies Research Articles

Safety profile of levonorgestrel intrauterine system: Analysis of spontaneous reports submitted to FAERS

The levonorgestrel-releasing intrauterine system (LNG-IUS) is an established, long-acting contraceptive option. With the widespread use of the LNG-IUS, drug-reported adverse events (AEs) have also garnered significant attention. In this study, we conducted a real-world analysis using the FDA's Adverse Event Reporting System (FAERS) database to assess the incidence of AEs associated with LNG-IUS use. Data from FAERS spanning from 2004Q1 to 2024Q1 were reviewed, with a focus on reports in which LNG-IUS was the primary suspected and secondary suspect drug. Signal detection was carried out utilizing Standardized MedDRA Queries (SMQ) and Preferred Terms (PT), with reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) employed to identify Signals of Disproportionate Reporting (SDR) for AEs. A positive SDR was defined when all three methods indicated significance. Analysis of 13 SMQs revealed notable SDRs in ear and eye disorders, cardiac arrhythmias, and lipodystrophy. Of the 61 suspected SDRs identified at the PT level, nearly half were not previously documented in labeling. Key potential signals of AEs associated with LNG-IUS use included increased heart rate, papilledema, idiopathic intracranial hypertension, cervical dysplasia, ruptured ovarian cyst, and uterine embedment and perforation. The findings underscore the importance of signal detection using FAERS data for identifying safety concerns related to LNG-IUS. Long-term observational studies are warranted to confirm and further elucidate these potential safety signals.

Detection of Increasing γ-Ray Emissions from 4FGL J1718.5+4237 with Fermi-LAT

We report a gradual brightening γ-ray source, 4FGL J1718.5+4237, in 0.1–500.0 GeV, which may be associated with a blazar NVSS J171822+423948 with a redshift of ∼2.7. We analyzed 15.25 yr of γ-ray data recorded by the Large Area Telescope on board the Fermi Gamma-ray Space Telescope and detected significant γ-ray emissions in the direction of the blazar with a test statistic (TS) of ∼135. Based on timing analysis using a 1 yr time bin, we have observed a gradual brightening in γ-ray emissions from the target. In our analysis, we categorize them into two states: Quiet (TS ∼ 0) and Loud (TS ∼ 226) states, with the distinction occurring in 2016 August (MJD 57602.69). From the Quiet state to the brightest period (the last data point), the γ-ray flux in 0.1–500.0 GeV increased by more than 12-fold from <0.2 × 10−8 photons cm−1 s−1 to 2.6 × 10−8 photons cm−1 s−1. Additionally, we studied the spectral properties in detail for the Loud state and the overall data. While no significant variation was detected, both exhibited a spectral index Γ of ∼2.6. The origin of the brightening γ-ray emissions from the target is not yet clear. Future long-term multi-wavelength observations and studies will provide insight into the astrophysical mechanisms of the target.

Rootstock selection for ‘Swatow’ mandarin trees grown at different locations throughout the Brazilian subtropics

Evaluating citrus rootstocks is of paramount importance in determining their suitability for a certain region and promoting resilience in orchards by increasing the genetic pool, thereby potentially contributing to a more strategic establishment of new plantings. This long-term field study (2000-2013) aimed to evaluate different rootstocks for ‘Swatow’ mandarin grown at two locations (Paranavaí and Londrina) in the Brazilian subtropics. Nine rootstocks were evaluated, including ‘Rangpur’ lime, ‘Swingle’ citrumelo, ‘Volkamer’ lemon, ‘Caipira DAC’ sweet orange, ‘Cleopatra’ and ‘Sunki’ mandarins, ‘Trifoliate’ orange, ‘Carrizo’, and ‘Fepagro C-13’ citranges. Trees were assessed for vegetative growth, yield, fruit quality, density, and yield estimates. The experimental design was a randomized block arranged in a 9 × 2 setting (rootstock × location) with 6 replicates and 4 trees per plot. ‘Swatow’ trees grew more vigorously in Londrina than Paranavaí, particularly for ‘Cleopatra’ and ‘Sunki’ pairings. Tree vigor was reduced with ‘Trifoliate’, resulting in higher tree density estimates and yield efficiency. This rootstock, along with ‘Rangpur’, ‘Swingle’, and ‘Carrizo’ provided superior yield to the scion. All tested rootstocks conferred good fruit quality. Fruits were larger and heavier in ‘Sunki’ pairings, showing higher soluble solids (SS) content along with ‘Caipira DAC’, ‘Trifoliate’, ‘Swingle’, and ‘Carrizo’ at both locations. Our findings confirm the suitability of ‘Trifoliate’ orange, ‘Carrizo’ citrange, or ‘Caipira DAC’ orange rootstocks as promising candidates for ‘Swatow’ mandarin cultivation in humid subtropical and analogous regions. Further investigations are invoked to improve the horticultural performance of ‘Swatow’ mandarin trees grafted onto these rootstocks.

Thermal and energy efficiency in 3D-printed Buildings: Review of geometric Design, materials and printing processes

Applying 3D printing in construction is a promising, sustainable alternative to conventional methods. However, the thermal and energy performance of 3D-printed structures remains underexplored, particularly regarding the interactions between geometric design, material selection, and printing parameters. This review addresses this gap by critically examining how main steps related to printing process impact on the thermal efficiency of 3D-printed buildings. Key findings indicate that material development needs to focus on mixes that balance thermal properties,printability,and structural integrity. The review demonstrates how optimising wall cross-sections and cavity shapes can reduce thermal conductivity and enhance energy efficiency. Innovative geometric designs, such as cellular and honeycomb structures, have shown improvements in thermal insulation. Optimising printing parameters such as extrusion rate and nozzle travel speed is crucial to minimise thermal bridges and reduce material anisotropy. Advanced numerical models, validated with experimental data and incorporating inhomogeneous porosity, anisotropy, and surface roughness, are essential for accurately predicting the thermal behaviour of 3D-printed structures. The review underscores the need for large-scale, long-term performance studies of 3D-printed structures under diverse climatic conditions. Additionally, developing standardised fabrication protocols and testing methods is essential to ensure consistent quality and broader adoption. Addressing these research gaps is crucial to fully realise the potential of 3D printing in sustainable construction and accelerate the adoption of additive manufacturing in the construction area.

Predictors of functional cure of chronic hepatitis B virus infection – A long-term follow-up study

Functional cure is an essential endpoint in the management of patients with chronic hepatitis B virus (HBV) infection. We evaluated the cumulative probability and predictors of functional cure in patients with chronic HBV infection after hepatitis B e antigen (HBeAg)-seroconversion. We retrospectively analyzed 413 (249 males and 164 females) initially HBeAg-positive chronic HBV-infected patients, who were followed up for a mean of 26.36 ± 0.53 years. All underwent HBeAg-seroconversion during follow-up. A functional cure was defined as durable HBsAg and HBV DNA loss without antiviral treatment for more than 24 weeks. After 10,888 person-years of follow-up, the cumulative probability of functional cure was 14.53% (n = 60). There were 24 (40%) subjects with functional cure after antiviral therapy. The annual functional cure rate was 0.55% per perperson-year, and increased to 0.96% per person-year after HBeAg-seroconversion. In subjects with functional cure, the HBsAg and HBV DNA titers after HBeAg-seroconversion were positively correlated with the time to functional cure (P < .001 and < .001, respectively). Multivariate Cox proportional hazard analysis of the cohort revealed that HBeAg-seroconversion at < 18 years of age, high genetic barrier nucleos(t)ide analogue(s) therapy before HBeAg-seroconversion, and a serum HBsAg titer < 1,000 IU/mL at 18 months after HBeAg-seroconversion were significant predictors of functional cure (P < .001, .001, and .001, respectively). In a cohort of chronic HBV-infected patients with long-term follow-up, HBeAg-seroconversion in childhood, high genetic barrier nucleos(t)ide analogue(s) therapy, and low HBsAg titers after HBeAg-seroconversion were significant predictors of functional cure.

Dapagliflozin in Heart Failure and Acute Myocardial Infarction: A Systematic Review of the Association in Diabetic Patients.

This systematic review explores the impact of dapagliflozin on heart failure (HF) and acute myocardial infarction (MI) in patients with type 2 diabetes mellitus. By analyzing recent studies, including both randomized controlled trials (RCTs) and retrospective analyses, this review provides insights into the cardiovascular effects of this sodium-glucose cotransporter 2 (SGLT2) inhibitor. The findings consistently demonstrate the benefits of dapagliflozin in reducing HF-related hospitalizations and improving outcomes for patients with established HF. These positive effects appear to extend beyond glycemic control, suggesting multiple mechanisms of action. The impact of dapagliflozin on acute MI outcomes is less clear, with mixed results across studies. Importantly, dapagliflozin shows promise in improving the quality of life of patients and is generally well-tolerated. The review suggests that dapagliflozin may play a significant role in managing cardiovascular risk in diabetic patients, particularly those with or at risk of HF. While the evidence is encouraging, the review also highlights areas requiring further investigation. These include determining the patient subgroups most likely to benefit from dapagliflozin, elucidating the precise mechanisms underlying its cardioprotective effects, and carrying out long-term outcome studies.

Metal-on-metal hip resurfacing arthroplasty: is it safe and reliable? A synopsis of the past, the present, and the future of HRA.

This paper discusses the existing literature in the field of metal-on-metal (MoM) hip resurfacing arthroplasty (HRA), the background (why was it developed), the past (what was the evidence leading to its rise and fall in clinical use), the present situation (why a potential resurgence), and the future directions for potential improvements. All literature relevant to MoM HRA was reviewed and summarized to provide a comprehensive summary. Furthermore, a detailed literature search was performed on PubMeD, MEDLINE, and Google Scholar to identify all clinical studies reporting a minimum 10 years of outcomes for modern MoM HRA devices from February 2018 to February 2023. In addition, joint registry data over the same time period, available in the public domain, was examined to extract related information on MoM HRA. Metal ions are present in almost all types of hip replacement; on the whole, however, the risk of revision for resurfacing due to metal-related pathologies is very low, but higher than in other types of bearings. There are studies that show that some brands of MoM resurfacing prostheses have achieved excellent clinical outcomes in long-term follow-up studies and are still in use although less commonly than in early 2000s. Use of alternative bearing surfaces has demonstrated excellent results in the short-term and a very critical long-term follow-up of these cases still will help establish their place in the hip arthroplasty world. HRA deserves a permanent place in the armamentarium of orthopedic surgeons and in the hand of experienced surgeons.

Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study

Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. For the Spanish translation of the abstract see Supplementary Materials section.

The Role of Natural Low Molecular Weight Dicarbonyls in Atherogenesis and Diabetogenesis.

This review summarises the data from long-term experimental studies and literature data on the role of oxidatively modified low-density lipoproteins (LDL) in atherogenesis and diabetogenesis. It was shown that not "oxidized" (lipoperoxide-containing) LDL, but dicarbonyl-modified LDL are atherogenic (actively captured by cultured macrophages with the help of scavenger receptors), and also cause expression of lectin like oxidized low density lipoprotein receptor 1 (LOX-1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) genes in endotheliocytes, which stimulate apoptosis and endothelial dysfunction. The obtained data allowed us to justify new approaches to pharmacotherapy of atherosclerosis and diabetes mellitus.

72122 - Mesh removal due to foreign body reaction and mesh infection in Groin hernia surgery: A long-term nationwide population-based register study

72122 - Mesh removal due to foreign body reaction and mesh infection in Groin hernia surgery: A long-term nationwide population-based register study

Fellows of the American Medical Informatics Association (FAMIA): Looking Back and Looking Ahead.

Over the past 30 years, the American Medical Informatics Association (AMIA) has played a pivotal role in fostering a collaborative community for professionals in biomedical and health informatics. As an interdisciplinary association, AMIA brings together individuals with clinical, research, and computer expertise and emphasizes the use of data to enhance biomedical research and clinical work. The need for a recognition program within AMIA, acknowledging applied informatics skills by members, led to the establishment of the Fellows of AMIA (FAMIA) Recognition Program in 2018. To outline the evolution of the FAMIA program and shed light on its origins, development, and impact. This report explores factors that led to the establishment of FAMIA, considerations affecting its development, and the objectives FAMIA seeks to achieve within the broader context of AMIA. The development of FAMIA is examined through a historical lens, encompassing key milestones, discussions, and decisions that shaped the program. Insights into the formation of FAMIA were gathered through discussions within AMIA membership and leadership, including proposals, board-level discussions, and the involvement of key stakeholders. Additionally, the report outlines criteria for FAMIA eligibility and the pathways available for recognition, namely the Certification Pathway and the Long-Term Experience Pathway. The FAMIA program has inducted five classes, totaling 602 fellows. An overview of disciplines, roles, and application pathways for FAMIA members is provided. A comparative analysis with other fellow recognition programs in related fields showcases the unique features and contributions of FAMIA in acknowledging applied informatics. Now in its sixth year, FAMIA acknowledges the growing influence of applied informatics within health information professionals, recognizing individuals with experience, training, and a commitment to the highest level of applied informatics and the science associated with it.

Inhibiting salt precipitation on the gas diffusion electrode surface in gas-phase CO2 electroreduction to formate by using an acidic anolyte

The gas-phase CO2 electroreduction to formate represents one of the most promising CO2 conversion processes due to its scalability, as the product concentration surpasses 30 % wt. However, the use of alkaline media anolytes, intended to improve the efficiency and selectivity of formate production, causes the carbonate and bicarbonate salts to precipitate over the Gas Diffusion Electrode (GDE). This precipitation clogs the porous structure, leading to a rapid loss of electrode stability. In this work, we address this issue by proposing the use of acid anolytes, based on K2SO4, to mitigate the precipitation of insoluble salt on the GDE structure, thereby achieving longer and more stable GDE operation times. Various anolyte concentrations and pHs are evaluated, with 0.3 M K2SO4 at pH 1, adjusted using H2SO4, providing the best compromise. This condition inhibited potassium carbonate and bicarbonate precipitation, as observed through XRD, SEM, and EDS analysis, while maintaining high CO2 electroreduction to formate performance, with a concentration of 69 g L−1, and a Faradaic Efficiency of 33 %. Furthermore, the anolyte flowrate per geometric area is optimized to maximize the system performance. At a flowrate of 0.85 mL min−1 cm−2, enhanced concentration of 88 g L−1 and a Faradaic Efficiency of 42 % are reached. Besides, long-term experiments demonstrated that GDEs used with alkaline conditions exhibit a larger deactivation constant (0.7652) compared to the GDEs used with acid anolytes (0.3891). This indicates that salt precipitation more rapidly reduces GDE performance under alkaline conditions. These results represent a promising advance in obtaining longer-lasting GDEs, which are crucial to successfully scaling up the CO2 electroreduction to formate.

Effects of Maternal SARS-CoV-2 Infection During Pregnancy on Fetal Development.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) outbreak in 2019 has necessitated investigating its potential adverse effects on pregnancy outcomes and fetal development. This study aimed to review the evidence on the impact of SARS-CoV-2 infection during pregnancy on fetal outcomes. Literatures since the outbreak of COVID-19 from PubMed and Web of Science were summarized in this narrative review, to show the effects of maternal SARS-CoV-2 infection during pregnancy on fetal development. SARS-CoV-2 infection during pregnancy can be transmitted vertically through the placenta, both in utero and perinatally, affecting the maternal-fetal immune interface and placental function. Viral infections during pregnancy have been linked to central nervous system development impairments and disorders such as autism. Changes in the structure and function of the respiratory, immune, and visceral systems have also been reported. SARS-CoV-2 infection during pregnancy has been linked with increased risks of stillbirth and preterm birth. However, the mechanisms involved remain unclear and may include cytokine storms, macrophage mediation, genetic mutations, methylation, and other epigenetic changes. Exploring the protective effects of antiviral treatment and other interventions in animal and clinical studies may help improve outcomes. SARS-CoV-2 infection during pregnancy activates the maternal-fetal immune interface through vertical transmission, and has short- and long-term effects on fetal development, including the central nervous system. Future long-term studies may help provide evidence that can inform interventions to reduce the risk of adverse outcomes.

Open Management of condylar head fractures: The first 50 cases: what have we learnt and where are we going?

This study evaluates a single surgeon’s experience the development of a practice in open treatment of intracapsular condylar fractures over three years at a tertiary maxillofacial trauma center. Enhanced dynamic peer reviewed longitudinal audit in keeping with adoption of elements of new clinical practice was instituted. This aimed to record and analyze clinical and functional outcomes at both surgeon and patient level. A retrospective review of patients treated for AOCMF-classified intracapsular fractures was conducted, utilizing an extended pre-auricular approach and positional screw fixation, with an emphasis on early joint mobilization and physiotherapy. The cohort consisted of 45 patients with 50 fractures, exhibiting a mean postoperative mouth opening of 32 mm, which statistically increased over time. Patient satisfaction was high, and the majority of radiological outcomes were deemed anatomical.In the patient cohort there were no permanent facial nerve injuries. Other postoperative complications were minimal, including one Frey’s syndrome and a 16% re-intervention rate primarily for hardware removal.The findings suggest that open treatment can be provided to achieve satisfactory early function as part of implementing an in-part novel procedure. The paper provides insight into establishing a new technique in both experiential and governance domains, as well as lessons learned. The high levels of patient and surgeon satisfaction confirm increasing levels of evidence supporting open reduction and fixation in these challenging injuries yet the study’s limitations include the absence of a control group and the potential non- generalizability due to the single-surgeon perspective. The study highlights the need to support colleagues providing this treatment and establish a national mentoring program to achieve this. At this point Long-term studies and a multi- center trial would follow to develop are suggested for a comprehensive understanding of the treatment’s efficacy and formal development of management protocols.

A broad-spectrum multiepitope vaccine against seasonal influenza A and B viruses in mice

Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines. This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19B-cell linear epitopes, 7 CD4+ T cells, and 11 CD8+ T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice. Upon lethal challenge with both seasonal circulating strains (H1N1, H3N2, BV, and BY) and historical strains (H1N1-PR8 and H3N2-X31), MEV demonstrated substantial protection against different influenza seasonal strains, with partial efficacy against historical strains. Notably, the increased germinal centre B cells and antibody-secreting cells, along with robust T cell immune responses, highlighted the comprehensive immune defence elicited by MEV. Elevated hemagglutinin inhibition antibody was also observed against seasonal circulating and historical strains. Additionally, mice vaccinated with MEV exhibited significantly lower counts of inflammatory cells in the lungs compared to negative control groups. Our results demonstrated the efficacy of a broad-spectrum MEV against influenza viruses in mice. Conducting long-term studies to evaluate the durability of MEV-induced immune responses and explore its potential application in diverse populations will offer valuable insights for the continued advancement of this promising vaccine. Funding bodies are described in the Acknowledgments section.

The Impact of Mindfulness Apps and Cognitive Behavioral Therapy on Prisoners' Mental Health

Prisoners' mental health and overall wellbeing are given significant consideration throughout the COVID-19 pandemic. The correctional facility's setting separates prisoners from the outside world, and their lack of access to modern medical care will result in depressive symptoms and other mental health issues. Prisons can benefit from the cost-effective and useful usage of CBT and mindfulness apps to enhance the mental health and general well-being of their inmates. This study provides an overview of possible ways to use smartphone apps to lessen mental health problems among prisoners. Applications of mindfulness have shown potential benefits in reducing mental health issues, including anxiety, depression, and stress. This paper reviews existing research on the effectiveness of these interventions and explores the feasibility of implementing such applications in prison settings. Although long-term effects are not yet well-documented, preliminary findings suggest that these apps could serve as a valuable tool for enhancing mental health care in correctional facilities. It is worthwhile to employ these applications as a pilot test to investigate their benefits further. By integrating technology with traditional practices and addressing challenges such as noncompliance and lack of personalization, prison systems can develop more effective and engaging mental health interventions. These efforts can contribute to better mental health outcomes, reduced recidivism, and a more rehabilitative prison environment. Future research should focus on long-term studies and strategies to improve adherence to online psychological treatments.

The LTAR Cropland Common Experiment in the Upper Chesapeake Bay.

Dairy production is a key agricultural enterprise in the Upper Chesapeake Bay (UCB) basin, where phosphorous (P) and nitrogen (N) loading contribute to eutrophication. Import of forages and grains and application of mineral fertilizers contribute to nutrient imbalances in the basin. The UCB Long-Term Agroecosystem Research Cropland Common Experiment aims to evaluate diverse crop rotations that minimize the need for imported feed, maximize year-round living cover, and reduce nutrient losses. UCB's plot-scale experiment was established in 2018, incorporating an ongoing cropping system study that was established by the Pennsylvania State University in 2010. An alternative dairy cropping rotation (including silage and grain corn [Zea mayes L.], alfalfa [Medicago sativa L.]/orchardgrass [Dactylis glomerata L.] mix, winter rye silage [Secale cereale L.], and sorghum-sudangrass [Sorghum × drummondii (Steud.) Millsp. & Chas]) that employed manure injection, integrated pest management, and less frequent manure application was compared to a prevailing, conventionally managed silage corn-alfalfa rotation with higher manure application rates. A field-scale experiment was established in 2019 to monitor alternative production practices (manure injection and avoidance of neonicotinoid seed treatment) and prevailing practices in three fields on a commercial dairy farm. Findings suggest that crop rotation diversification, manure injection, and integrated pest management have the potential to increase the economic and environmental sustainability of dairy cropping systems, but long-term evaluation is needed for confirmation.

Effects of several long-term soil health treatments on populations of Pratylenchus penetrans and the soil microbial community

AbstractSoil suppressiveness can reduce the damage by plant parasitic nematodes (PPN) in agricultural soils and is conveyed by the activity of soil microorganisms. While natural suppressiveness has been reported, it is still poorly understood if soil suppressiveness can be elicited by manipulating the soil microbial community. In the present study we assessed the number of the Pratylenchus penetrans (Pp) and the bacterial and fungal community composition over 7 years in a long-term soil health experiment. The field experiment consisted of an organic and conventional agricultural land management system and three soil health treatments (SHT): an untreated control (CT), anaerobic disinfestation (AD) and a combination of marigold cover cropping, compost and chitin amendment (CB). The land management systems were kept continuously, while the soil health treatments were applied only twice in seven years. The microbial community significantly differed between the organic and conventional system, but there was no significant difference in Pp numbers between the two systems. However, both the CB treatment and to a lesser extent the AD treatment reduced Pp numbers and increased yield with the effect being the strongest in the years immediately after the treatment. Accordingly, both the bacterial and fungal community differed significantly between the treatments, the differences being largest in the years after the treatments. Notably, the CB treatment elicited both long-term changes in the microbial community and a reduction of Pp numbers lasting for at least three years. These results indicated that a combination of treatments can lead to an altered soil microbial community in combination with persisting suppressiveness of Pp.

Long-term safety and efficacy of filgotinib for the treatment of moderately to severely active ulcerative colitis: Interim analysis from up to 4 years of follow-up in the SELECTION open-label long-term extension study.

Filgotinib, an oral, once-daily, Janus kinase 1 preferential inhibitor, is an approved treatment for moderately to severely active ulcerative colitis. The aim of this study is to assess the safety and efficacy of continued filgotinib therapy over ~4 years in the long-term extension of the phase 2b/3 SELECTION trial (SELECTIONLTE; NCT02914535). In this interim analysis of SELECTIONLTE, SELECTION completers (week 10 responders to filgotinib who completed the maintenance study) continued their assigned treatment (double-blind filgotinib 200 mg [FIL200] or filgotinib 100 mg) and SELECTION week 10 non-responders received open-label FIL200. We assessed safety by adverse events (AEs), and efficacy by partial Mayo Clinic Score (pMCS), inflammatory biomarkers and health-related quality of life (HRQoL). We compared safety and efficacy between achievers and non-achievers of a multi-component endpoint, comprehensive disease control (CDC), comprising symptomatic, endoscopic, inflammatory biomarker and HRQoL improvements. Data for completers (n = 250) and non-responders (n = 372) were reported for ≤202 weeks. AE occurrences were low and consistent with previous analyses. The as-observed proportion of FIL200-treated patients in pMCS, biomarker and HRQoL remission during SELECTIONLTE remained high among completers (week 144: 80.0%, 86.4% and 86.0%, respectively) and increased among non-responders (week 192: 62.1%, 76.7% and 59.3%, respectively). Significantly higher proportions of CDC achievers at SELECTION week 58 achieved pMCS, IBDQ and corticosteroid-free pMCS remission than non-achievers, up to LTE week 96. Filgotinib induced and maintained symptomatic remission and improved HRQoL over 4 years. Safety results showed a proven long-term benefit-risk profile. FIL200-treated CDC achievers had better long-term outcomes than non-achievers.

From fire to recovery: temporal-shift of predator–prey interactions among mammals in Mediterranean ecosystems

AbstractFires are becoming increasingly frequent, intense, severe and prolonged worldwide, and such situation is worsening. As a result, extreme fire conditions will increase, with consequences for wildlife, including increased mass mortality and changes in trophic relationships in natural communities. This intensification is expected to be particularly pronounced in the Mediterranean ecosystems. In this scoping review, we summarized current knowledge and gaps in understanding the effects of fires on wildlife, focusing on predator–prey interactions. These interactions play a critical role in animal communities and their understanding is fundamental for appropriate management and conservation. Mammals were chosen as a model group because of their remarkable ecological role. We grouped and analysed the post-wildfire changes in the predator–prey relationships into three-time intervals: immediate, short- and long-term effects. This is relevant as vegetation restoration, by altering cover and habitat structure, may affect hunting strategies and anti-predatory behaviour. Our review showed that studies generally had several limitations, the most common of which were the lack of replication, the strong geographical bias, and the focus on few target species. Nevertheless, we could formally describe how fire affects predator–prey relationships in Mediterranean ecosystems through processes that exert different cascading effects at different times after the fire event. We encourage long-term studies on communities, including as many components of the food chain as possible, using an interdisciplinary approach, and prioritising investigations in high-risk ecosystems.