A note on the effect of expected changes in monetary policy on long-term interest rates

The ability of monetary policy to affect long-term interest rates is of central importance for economics and finance. Several recent studies have shown that long-term interest rates are virtually unaffected by monetary policy. This paper develops a statistical methodology to identify the expected and unexpected changes in monetary policy as measured by the federal funds rate. The empirical evidence shows that expected changes in the funds rate cause stronger and more significant movements in the long-term rates. Further, ignoring such asymmetry can erroneously generate the insignificant responses of long-term interest rates to the changes in the monetary policy.Long-term interest rate, monetary policy, asymmetry

Exploring the relationship between volunteering and hospice sustainability in the UK:A theoretical model

Aim: To explore the relationship between volunteering and the sustainability of UK voluntary hospices.Methods: A narrative literature review was conducted to inform the development of a theoretical model. Eight databases were searched: CINAHL (EBSCO), British Nursing Index, Intute: Health and Life Sciences, ERIC, SCOPUS, ASSIA (CSA), Cochrane Library and Google Scholar.Results: A total of 90 documents were analysed. Emerging themes included the importance of volunteering to the hospice economy and workforce, the quality of services, and public and community support. Findings suggest that hospice sustainability is dependent on volunteers; however, the supply and retention of volunteers is affected by internal and external factors.Conclusions: A theoretical model was developed to illustrate the relationship between volunteering and hospice sustainability. It demonstrates the factors necessary for hospice sustainability and the reciprocal impact that these factors and volunteering have on each other. The model has a practical application as an assessment framework and strategic planning tool

Capacitance analysis for volume reduction based on integrated buck and buck-boost LED driver

This work was supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES/PROEX) - Finance Code 001, PRPG/UFSM, INCT-GD, CAPES proc 23038.000776/2017-54, CNPQ proc 465640/2014-1 and FAPERGS proc 17/2551-0000517-1 and in part by the Spanish government under grants PID2019-105568RB-I00 and TED2021-129372B-I00

Differential Analysis of Ovarian and Endometrial Cancers Identifies a Methylator Phenotype

Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid ovarian tumors indicates that intervention strategies could be developed to specifically address subtypes of epithelial ovarian cancer

A qualitative study exploring perceptions and attitudes of community pharmacists about extended pharmacy services in Lahore, Pakistan

Background In recent decades, community pharmacies reported a change of business model, whereby a shift from traditional services to the provision of extended roles was observed. However, such delivery of extended pharmacy services (EPS) is reported from the developed world, and there is scarcity of information from the developing nations. Within this context, the present study was aimed to explore knowledge, perception and attitude of community pharmacists (CPs) about EPS and their readiness and acceptance for practice change in the city of Lahore, Pakistan. Methods A qualitative approach was used to gain an in-depth knowledge of the issues. By using a semi-structured interview guide, 12 CPs practicing in the city of Lahore, Pakistan were conveniently selected. All interviews were audio-taped, transcribed verbatim, and were then analyzed for thematic contents by the standard content analysis framework. Results Thematic content analysis yielded five major themes. (1) Familiarity with EPS, (2) current practice of EPS, (3) training needed to provide EPS, (4) acceptance of EPS and (5) barriers toward EPS. Majority of the CPs were unaware of EPS and only a handful had the concept of extended services. Although majority of our study respondents were unaware of pharmaceutical care, they were ready to accept practice change if provided with the required skills and training. Lack of personal knowledge, poor public awareness, inadequate physician-pharmacist collaboration and deprived salary structures were reported as barriers towards the provision of EPS at the practice settings. Conclusion Although the study reported poor awareness towards EPS, the findings indicated a number of key themes that can be used in establishing the concept of EPS in Pakistan. Over all, CPs reported a positive attitude toward practice change provided to the support and facilitation of health and community based agencies in Pakistan

Retrospective analysis of custom 3D-printed drill guides and titanium plate use in spinal stabilization of eleven dogs

IntroductionCongenital vertebral malformations are common developmental abnormalities in screw-tailed brachycephalic dog breeds. Subsequent vertebral instability and/or vertebral canal stenosis caused by these malformations can lead to spinal cord compression manifesting in pain, paraparesis, ataxia and/or paralysis. Various methods for spinal stabilization are in common use. However, these are without significant risk due to narrow margins of surgical error and variable vertebral anatomy. We evaluate a novel method for spinal stabilization where a custom 3D-printed plate is created and surgically fitted to the patient’s spine using custom 3D-printed drill guides.ObjectiveTo describe the surgical technique and short-term outcomes in patients treated with custom 3D-printed plates and drill guides.MethodA retrospective analysis of 11 dogs from two referral hospitals which underwent this procedure was undertaken. Post-operative CT scans were assessed for spinal canal screw perforation using the modified Zdichavsky classification. Pre-operative and post-operative neurological status were assessed using the Modified Frankel Scale and the surgical technique including post-operative imaging and recovery findings were described.ResultsOptimal screw placement (grade I) was achieved in 63% of placed screws across the eleven dogs. Partial penetration of the medial wall (grade IIa) was observed in 3% of screws and partial penetration of the lateral wall (grade IIIa) was observed in 29% of screws. Full penetration of the lateral pedicle wall (grade IIIb) was observed in 5% of screws and no screws fully penetrated the medial vertebral wall (grade IIb).DiscussionWe demonstrated that custom 3D-printed drill guides and titanium plates can provide a safe peri-operative alternative for surgical spinal stabilization of dogs with vertebral column instability due to congenital vertebral malformations. Further research is needed to describe long-term outcomes of this surgical technique on patient health

Efficacy of Mcl-1 Inhibitors in Multiple Myeloma Cells Resistant to Bortezomib

Multiple myeloma (MM) is a type of cancer that affects plasma B cells. Patients with MM often experience frequent relapses and can develop resistance to drugs. As a medical researcher, it is important to understand the role of Mcl-1 in preventing intrinsic apoptosis and drug resistance. Mcl-1 belongs to the anti-apoptotic subgroup of Bcl-2 family proteins and plays a crucial role in these processes. Mcl-1 plays a crucial role in driving disease progression and contributing to drug resistance in MM. It has been observed that there is an increased expression of Mcl-1 in 52% of patients with MM during diagnosis, which further rises to 81% during relapse. Thus, researchers are investigating the potential of Mcl-1 inhibitors as a viable treatment option for patients with MM, particularly those who have not responded to previous therapies. Proteasome inhibitor Bortezomib (BTZ) is commonly prescribed as the initial treatment for MM, but unfortunately, patients eventually develop resistance to it. For this study, we created cells that are resistant to BTZ in order to explore the potential mechanisms behind the development of resistance. These cells have been treated with BTZ over a period of 6 months. Regrettably, there are currently no Mcl-1 inhibitors that have been approved by the FDA. However, there are several agents, such as S63845, AZ5991, and VU661013, that are currently undergoing clinical trials. Interestingly, Mcl-1 inhibitors demonstrated effectiveness against sensitive cells but showed a decrease in efficacy against BTZ resistant cells. Our research indicates that cells resistant to BTZ require a higher concentration of Mcl-1 inhibitors in order to undergo cell death. This suggests that these resistant cells may possess a compensatory mechanism that stabilizes the Mcl-1 protein and alters the effectiveness of Mcl-1 inhibitors in treatment. It is worth noting that the anti-apoptotic Bcl-2 protein exhibits heightened expression in resistant cells, even when inhibitors are present. This observation may provide valuable insights into a potential resistance mechanism and calls for further investigation into the compensatory mechanisms that play a crucial role in drug resistance

A case of semi-combusted pregnant female in the Phoenician-Punic necropolis of Monte Sirai (Carbonia, Sardinia, Italy)

We present a case of a pregnant woman with the fetus skeletal remains in situ, belonging to the Phoenician-Punic necropolis of Monte Sirai (Sardinia, Italy). The burial dates back to the late 6th to early 5th century BCE. Of the unborn fetal cases documented in the literature this is amongst the oldest four and it represents the first documented case of a pregnant woman in the Phoenician and Punic necropolis literature. A physico-chemical investigation of bones combining X-ray diffraction and Fourier transform-infrared spectroscopy suggests that the female skeleton and fetus were subjected to an incomplete heat treatment according to a funerary practice, perhaps limited to the period of early 5th century BCE, that appears to be peculiar to this site

Validated Spectrophotometric Methods for the Determination of Nabumetone in Tablets Dosage Form Using Three Dinitrobenzene Reagents

ABSTRACT Three spectrophotometric methods have been described for the determination of nabumetone (NAB) in its tablets dosage form. The methods are based on the reaction of nabumetone with three dinitrobenzene reagents, namely, m-dinitrobenzene (DNB), 1-chloro-2,4-dinitrobenzene (CDNB) and 1-fluoro-2,4-dinitrobenzene (FDNB) in alkaline medium (alcoholic potassium hydroxide solution). The studied reactions depend on the tendency of these dinitrobenzene reagents to react with the active methylene adjacent to the carbonyl group of the drug. Illustrative proposed pathways showing the reaction of NAB with the three dinitrobenzene reagents were presented. Spectrophotometric measurements were achieved by recording the absorbances at 580, 573 and 574 nm for the reaction with DNB, CDNB and FDNB respectively. Different experimental parameters affecting development and stability of the produced colors were optimized. The three methods were validated with respect to linearity, ranges, precision, accuracy and limits of detection and quantification. Beer's law was obeyed in the concentration ranges of 2-10, 40-240 and 10-50 µg/mL for DNB, CDNB and FDNB methods respectively with correlation coefficient values not less than 0.9994. In addition, detection limits of NAB were 0.27, 8.54 and 2.04 µg/mL for DNB, CDNB and FDNB methods, respectively. The proposed methods were successfully applied for assay of the drug in its tablets dosage form. Recovery data obtained by the proposed methods were favorably compared with those obtained by a reported spectrophotometric method

Comparative safety of prescribed Esketamine and ketamine in relation to renal and urinary disorders : A pharmacovigilance perspective

© 2024 The Author(s). Published by Elsevier Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial 4.0 International License (CC BY-NC), https://creativecommons.org/licenses/by-nc/4.0/Intranasal esketamine, approved with oral antidepressants for adults with treatment-resistant depression (TRD), is the S-enantiomer of ketamine and has higher potency and affinity for N-Methyl-d-Aspartate receptors. Administered intranasally, it offers rapid absorption and onset, essential for severe depressive symptoms or suicidal impulses. Comparative studies on esketamine and ketamine's urological safety profiles show esketamine has lower or comparable risks of renal and urinary disorders. Ketamine, however, has documented cases of nephrotoxicity and severe urological issues in recreational users. The study aims to further evaluate and compare these profiles against other antidepressants and antipsychotics using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) data. ADR cases were reported to the FDA up to May 12, 2024, being drugs listed including esketamine, ketamine, quetiapine, aripiprazole, olanzapine, risperidone, citalopram, escitalopram, paroxetine, fluoxetine, sertraline, duloxetine, venlafaxine, amitriptyline, and clomipramine. Risperidone showed the highest ADRs (107,418) and serious cases (71,515), with significant renal and urinary disorders reported, including acute kidney injury and urinary incontinence. Olanzapine, quetiapine, and aripiprazole also had high serious ADRs. Venlafaxine and fluoxetine were notable among antidepressants for acute kidney injury. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis revealed ketamine had higher odds of renal and urinary disorders compared to other drug classes, while esketamine had lower or comparable odds. The data suggest a relatively favorable tolerability profile for these drugs, especially esketamine. However, the results highlight the necessity for more extensive studies to evaluate long-term safety and optimize treatment protocols.Peer reviewe