Background: As the incidences of preterm births and surgical cases increases, so do cases of neonatal sepsis in CMH. Furthermore, the common etiology of neonatal sepsis are multidrug-resistant bacteria which increase the risk of mortality. Cefepime is a fourth-generation cephalosporin which is increasingly being utilized in NICUs. Theoretically, continuous infusion of beta lactam antibiotics could maximize the time- dependent bactericidal activity and improve the probability of target attainment. This study aims to determine the effectiveness and safety of continuous cefepime administration in managing sepsis. Methods: This is retrospective cohort study on infants who suspected late onset sepsis from 2021 to 2023. The independent variables are continuous infusion and intermittent infusion, with outcomes including mortality rate, reduction in septic markers, use of antibiotic combinations, duration of antibiotic use, and renal function test. Result: There were 106 subjects receiving cefepime (56 continuous and 50 intermittent infusions; p>0.05). No significant differences in demographic data such as gestational age, prematurity condition, birth weight, and surgical conditions were found between the two methods. Out of 66 subjects with proven sepsis, 28% were classified as MDR, 12% as XDR, and 16% as PDR. No difference in sepsis-related mortality outcomes was observed between the two methods (64.3% vs. 70%; p=0.532). Continuous administration reduced C-reactive protein (80.52 vs. 51.69 mg/L; p=0.000) and procalcitonin (11.9 vs. 6.72 ng/mL; p=0.008) more effectively than intermittent. In surgical cases, continuous administration reduced the risk of multidrug therapy (RR 0.5 CI 95% 0.243-0.902; p=0.045). There was no difference renal function impairment between two methods. Conclusion: Cefepime continuous infusion can significantly reduce infection markers compared to intermittent administration. In surgical cases, continuous cefepime administration reduces the risk of multidrug therapy. The use of continuous cefepime can be considered as part of antibiotic stewardship in the NICU.

G protein-coupled receptors (GPCRs) are involved in many physiological and pathophysiological processes. Conventional pharmacological models categorize the typology of pharmacologic ligands as agonists or antagonists. Biased agonism is a relatively newer pharmacodynamic characteristic that has potential to optimize therapeutic efficacy while minimizing adverse effects in psychiatric and neurological treatments. We conducted a narrative literature review of articles obtained from PubMed, Embase, and MEDLINE from inception to April 2025, focusing on pharmacologic antagonism (i.e., competitive, noncompetitive, uncompetitive) and agonism (i.e., full, partial, inverse, superagonism, biased). Primary and secondary articles defining these concepts were included, provided they addressed pharmacologic (rather than chemical) antagonism and agonism. Distinct mechanisms of antagonism and agonism were identified, each contributing nuanced receptor modulation beyond the conventional models. Notably, biased agonism facilitates targeted intracellular signaling (e.g., G protein- versus β-arrestin–mediated). Use cases demonstrate relatively greater efficacy (e.g., incretin receptor agonist, tirzepatide) and improved safety (e.g., serotonergic psychedelics, opioids). Biased agonism provides a potential avenue for future drug development, with emerging preclinical evidence suggesting potential to differentially activate intracellular pathways and thereby improve efficacy and safety profiles of psychopharmacologic agents—pending clinical validation. Future research vistas should aim to rigorously assess the long-term outcomes of biased agonism, explicitly addressing individual variability in receptor signaling and therapeutic response.

Finger weeders were first developed in the 1950s and have since been widely adopted by farmers to improve physical weed control (PWC) within crop rows. Research on finger weeders has largely been comparative, with most studies identifying a top-performing weed control practice among various physical or chemical treatments. Weeding tool performance, however, is often highly variable, affected by tool design and adjustment, soil conditions, and both weed and crop species and size. Finger weeder operating settings have not been systematically tested to determine whether they could optimize tool performance. In this project, field and soil bin experiments examined the effects of finger weeder angle, spacing, and speed on weed control efficacy and weed/crop selectivity. Three finger weeder angles were tested: 108°, which removed soil near the crop; 90°, typical for most commercial tools; and 68°, which moved soil into the crop row. Three spacings and speeds were compared: fingers overlapping (−0.6 cm), touching (0 cm), or spaced apart (2.5 cm); and 4, 7, and 9 km h−1. In both the field and soil bin, finger weeders set at a 68° angle resulted in the greatest efficacy. Decreasing finger spacing and increasing speed improved efficacy in soil bin experiments, as expected, but spacing and speed effects were not detected in the field. The experimental soil bin system shows promise for PWC testing, possibly offering insights that could not be detected in more variable field conditions.

The aim of this paper is to challenge the argument that says, as judges are not elected, they have weaker or no democratic legitimacy when compared to legislators. This paper draws on dicta from Laws LJ, as he then was, in the Divisional Court case of Cart v Upper Tribunal, to offer two reasons why this is false. Call these the efficacy and equality principles of representation. The claim here is that without an independent judiciary, legislators cannot legislate or legislate in a way that applies equally. So, without an independent judiciary, the democratic legitimacy of a legislature is weakened or disappears. This argument makes a legal difference, but the kind of legal difference it makes varies between jurisdictions. This paper focuses on one difference the democratic legitimacy of judges makes in the UK: the extent to which Parliament can oust judicial review for error of jurisdiction.

Clethodim is an important herbicide for managing Texas panicum. However, its efficacy is influenced by the weed size and environmental stress during application. Therefore, field and greenhouse studies were conducted in 2023 and 2024 to evaluate clethodim efficacy on various Texas panicum sizes. Clethodim was applied at Texas panicum heights ranging from 5 cm to 60 cm. A sequential application was applied 2 wk after the initial treatment for larger weed sizes (15 to 60 cm). In separate field and greenhouse studies, nonionic surfactant (NIS), crop oil concentrate (COC), methylated seed oil (MSO), COC + ammonium sulfate (AMS), and MSO + AMS adjuvants were mixed with clethodim to determine efficacy on 10- to 15-cm and 20- to 30-cm Texas panicum. In the weed size study, sequential applications of clethodim increased Texas panicum control compared to a single application. At the 10- to 15-cm growth stage, a single application provided 90% Texas panicum control, whereas the sequential treatment improved control from 76% to 91% at the 15- to 20-cm growth stage. However, clethodim efficacy declined as Texas panicum size increased across single and sequential treatments. In the adjuvant studies, clethodim plus COC, COC + AMS, or MSO + AMS provided 91%, 93%, and 90% control at the 10- to 15-cm growth stage, respectively; however, efficacy decreased for 20- to 30-cm Texas panicum. Texas panicum efficacy was higher for clethodim plus MSO + AMS than clethodim plus MSO; however, AMS did not increase clethodim + COC efficacy. Overall, Texas panicum control with clethodim was most effective when weed height was 15 cm or less. A sequential application of clethodim was required for larger Texas panicum (>15 cm). Clethodim plus COC or MSO + AMS provided the greatest control of Texas panicum. This study demonstrated that successful Texas panicum management depends on applying clethodim at the optimum size and selecting the appropriate oil-based adjuvant especially at larger Texas panicum sizes.

Tetflupyrolimet (Dodhylex™ Active, FMC Corporation) is a novel herbicide inhibiting de novo pyrimidine biosynthesis that controls grassy weeds preemergence in rice (Oryza sativa L.) production. Field trials were conducted from 2021 to 2024 to evaluate turfgrass tolerance to tetflupyrolimet applications for annual bluegrass (Poa annua L.) and smooth crabgrass [Digitaria ischaemum (Schreb.) Schreb. ex Muhl.] control. Tolerance was evaluated on seven turfgrass species, including creeping bentgrass (Agrostis stolonifera L.), Kentucky bluegrass (Poa pratensis L.), tall fescue [Schedonorus arundinaceus (Schreb.) Dumort.; syn.: Festuca arundinacea Schreb.], hybrid bermudagrass [Cynodon dactylon (L.) Pers. × Cynodon transvaalensis Burtt-Davy], and manilagrass [Zoysia matrella (L.) Merr.] at various mowing heights ranging from 3.8 to 12.5 mm. Separate experiments were conducted on each turfgrass species to evaluate tolerance in both fall and spring. Tetflupyrolimet was applied at rates of 0, 25, 50, 100, 200, 400, 800, 1600, 3200, or 6400 g ai ha−1. No injury was observed on any warm-season turfgrass species in either season, whereas cool-season grass tolerance varied among species each season; however, cool-season turfgrass tolerance for all species was greater in spring than fall. While efficacy of tetflupyrolimet (400 g ha−1) for preemergence D. ischaemum control varied among years, mixtures of tetflupyrolimet (400 g ha−1), pyroxasulfone (128 g ai ha−1), and rimsulfuron (35 g ai ha−1) applied preemergence or early postemergence effectively controlled multiple-resistant P. annua in both seasons. Overall, these findings highlight that warm-season turfgrasses are highly tolerant of tetflupyrolimet applications for P. annua or D. ischaemum control.

Interpersonal psychotherapy (IPT) and antidepressant medications are both first-line interventions for adult depression, but their relative efficacy in the long term and on outcome measures other than depressive symptomatology is unknown. Individual participant data (IPD) meta-analyses can provide more precise effect estimates than conventional meta-analyses. This IPD meta-analysis compared the efficacy of IPT and antidepressants on various outcomes at post-treatment and follow-up (PROSPERO: CRD42020219891). A systematic literature search conducted May 1st, 2023 identified randomized trials comparing IPT and antidepressants in acute-phase treatment of adults with depression. Anonymized IPD were requested and analyzed using mixed-effects models. The prespecified primary outcome was post-treatment depression symptom severity. Secondary outcomes were all post-treatment and follow-up measures assessed in at least two studies. IPD were obtained from 9 of 15 studies identified (N = 1536/1948, 78.9%). No significant comparative treatment effects were found on post-treatment measures of depression (d = 0.088, p = 0.103, N = 1530) and social functioning (d = 0.026, p = 0.624, N = 1213). In smaller samples, antidepressants performed slightly better than IPT on post-treatment measures of general psychopathology (d = 0.276, p = 0.023, N = 307) and dysfunctional attitudes (d = 0.249, p = 0.029, N = 231), but not on any other secondary outcomes, nor at follow-up. This IPD meta-analysis is the first to examine the acute and longer-term efficacy of IPT v. antidepressants on a broad range of outcomes. Depression treatment trials should routinely include multiple outcome measures and follow-up assessments.

We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics (AAPs) for the treatment of bipolar patients with depressive episodes. Sixteen randomized controlled trials with 7234 patients treated by one of the five AAPs (cariprazine, lumateperone, lurasidone, olanzapine, and quetiapine) were included. For the response rate (defined as an improvement of ≥50% from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), all AAPs were more efficacious than placebo. For the remission rate (defined as the endpoint of MADRS ≤12 or ≤ 10), cariprazine, lurasidone, olanzapine, and quetiapine had higher remission rates than placebo. In terms of tolerability, olanzapine was unexpectedly associated with lower odds of all-cause discontinuation in comparison with placebo, whereas quetiapine was associated with higher odds of discontinuation due to adverse events than placebo. Compared with placebo, lumateperone, olanzapine, and quetiapine showed higher odds of somnolence. Lumateperone had a lower rate of ≥ weight gain of 7% than placebo and other treatments. Olanzapine was associated with a significant increase from baseline in total cholesterol and triglycerides than placebo. These findings inform individualized prescriptions of AAPs for treating bipolar depression in clinical practice.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80 mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n = 587; placebo, n = 585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p < 0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.

Positively experienced relationships with family, partners and friends are the most important source of meaning in life for older persons. At the same time, Western countries are confronted with a growing number of socially isolated older adults who lack those relationships. This study aims to explore whether and how older adults who live in social isolation experience meaning in life. Data were collected via in-depth, semi-structured interviews with 24 socially isolated older adults, ranging in age from 62 to 94, all living in Rotterdam, The Netherlands. The criterion-based sampling of participants took place in close consultation with social workers of a mentoring project for socially isolated older adults. Follow-up interviews with 22 participants improved the credibility of findings and contributed to the breadth and depth of the researched casuistry. Data were analysed using an analytical framework based on seven needs of meaning identified by Baumeister (purpose, values, efficacy, self-worth) and Derkx (coherence, excitement, connectedness). The study demonstrates that isolated older adults may find anchors for meaning in life, although not all needs for meaning are satisfied, and there can also be tension between different needs. The needs-based model provides concrete distinctions for enabling care-givers to recognise elements of meaning.