Background: Patient-perpetrated sexual harassment toward health care providers is common and adversely affects provider well-being, workforce outcomes, and patient care. Organizational climate for sexual harassment-shared perceptions about an organization's practices, policies, and procedures-is one of the strongest predictors of harassment prevalence. We conducted a pilot survey assessing provider perceptions of the Veterans Health Administration (VA)'s climate related to patient-perpetrated sexual harassment.
View Article and Find Full Text PDFSelective inhibition of the RGD (Arg-Gly-Asp) integrin αvβ1 has been recently identified as an attractive therapeutic approach for the treatment of liver fibrosis given its function, target expression, and safety profile. Our identification of a non-RGD small molecule lead followed by focused, systematic changes to the core structure utilizing a crystal structure, modeling, and a tractable synthetic approach resulted in the identification of a potent small molecule exhibiting a remarkable affinity for αvβ1 relative to several other integrin isoforms measured. Azabenzimidazolone demonstrated antifibrotic efficacy in an rat liver fibrosis model and represents a tool compound capable of further exploring the biological consequences of selective αvβ1 inhibition.
View Article and Find Full Text PDFSmall-molecule antivirals that prevent the replication of the SARS-CoV-2 virus by blocking the enzymatic activity of its main protease (Mpro) are and will be a tenet of pandemic preparedness. However, the peptidic nature of such compounds often precludes the design of compounds within favorable physical property ranges, limiting cellular activity. Here we describe the discovery of peptide aldehyde Mpro inhibitors with potent enzymatic and cellular antiviral activity.
View Article and Find Full Text PDFIn 2022, 23 new small molecule chemical entities were approved as drugs by the United States FDA, European Union EMA, Japan PMDA, and China NMPA. This review describes the synthetic approach demonstrated on largest scale for each new drug based on patent or primary literature. The synthetic routes highlight practical methods to construct molecules, sometimes on the manufacturing scale, to access the new drugs.
View Article and Find Full Text PDFThis study aimed to explore player and stakeholder perceptions of the role of nutrition in influencing the development of male academy soccer players. Semi-structured interviews (28 ± 13 mins in length) were conducted with 31 participants from an English category one academy, including players (Youth Development Phase, YDP: = 6; Professional Development Phase, PDP: = 4), parents/guardians ( = 10), coaches ( = 3), sport scientists ( = 3), physiotherapists ( = 3), and catering ( = 2). Via reflexive thematic analysis, data demonstrate an apparent lack of understanding and awareness on the role of nutrition in influencing player development, especially in relation to growth, maturation and reducing injury risk.
View Article and Find Full Text PDFDespite the prevalence of deception, people rarely doubt others' sincerity. However, indirect evaluations of liars and truth-tellers may differ even in the absence of suspicion about veracity. Across three studies, we provide evidence for the truth attraction effect in two samples of target stimuli and three samples of participant judges.
View Article and Find Full Text PDFEach year, new drugs are introduced to the market, representing structures that have affinity for biological targets implicated in human diseases and conditions. These new chemical entities (NCEs), particularly small molecules and antibody-drug conjugates, provide insight into molecular recognition and serve as potential leads for the design of future medicines. This annual review is part of a continuing series highlighting the most likely process-scale synthetic approaches to 35 NCEs that were first approved anywhere in the world during 2021.
View Article and Find Full Text PDFBackground: Ankle fractures are among the most common injuries treated by orthopaedic surgeons, yet little guidance exists in postoperative protocols for ankle fractures concerning time of immobilization. Here, we aim to investigate the association between early mobilization and patient-reported outcomes. Our null hypothesis was that no difference in Patient-Reported Outcomes Measurement Information System (PROMIS) scores would be identified in patients when comparing the effect of time of immobilization.
View Article and Find Full Text PDFNew drugs introduced to the market are privileged structures that have affinities for biological targets implicated in human diseases and conditions. These new chemical entities (NCEs), particularly small molecules and antibody-drug conjugates (ADCs), provide insight into molecular recognition and simultaneously function as leads for the design of future medicines. This Review is part of a continuing series presenting the most likely process-scale synthetic approaches to 44 new chemical entities approved for the first time anywhere in the world during 2020.
View Article and Find Full Text PDFBackground: Management of neutropenic fever in high-risk haematology patients is challenging; there are often few localising clinical features, and diagnostic tests have poor sensitivity and specificity. We aimed to compare how [F]flurodeoxyglucose ([F]FDG)-PET-CT scans and conventional CT scans affected the guidance of antimicrobial management and the outcomes of patients with persistent or recurrent neutropenic fever.
Methods: We did a multicentre, open-label, phase 3, randomised, controlled trial in two tertiary referral hospitals in Australia.
Background: Meaningful engagement of patients in health research has the potential to increase research impact and foster patient trust in healthcare. For the past decade, the Veterans Health Administration (VA) has invested in increasing Veteran engagement in research.
Objective: We sought the perspectives of women Veterans, VA women's health primary care providers (WH-PCPs), and administrators on barriers to and facilitators of health research engagement among women Veterans, the fastest growing subgroup of VA users.
We propose a search for low mass dark matter particles through momentum recoils caused by their scattering from trapped, nanometer-scale objects. Our projections show that even with a modest array of femtogram-mass sensors, parameter space beyond the reach of existing experiments can be explored. The case of smaller, attogram-mass sensors is also analyzed-where dark matter can coherently scatter from the entire sensor-enabling a large enhancement in the scattering cross-section relative to interactions with single nuclei.
View Article and Find Full Text PDFTo audit the current provision of performance nutrition services provided to male adolescent players within academies from the English soccer leagues. Practitioners from all 89 academies (status categorised as one-four according to the Elite Player Performance Plan, EPPP) completed an online survey to audit: a) job role/professional accreditation status of persons delivering nutrition support, b) activities inherent to service provision, c) topics of education, d) on-site food, fluid and supplement provision and e) nutritional related data collected for objective monitoring. More full-time accredited nutritionists are employed within category one (14/26) versus category two (0/18), three (1/41) and four (0/4).
View Article and Find Full Text PDFWhile agreement between clients and their clinicians on therapy goals has frequently been investigated as a process-level variable (i.e., working alliance), dyadic convergence on presenting concerns is also important for initial case formulation.
View Article and Find Full Text PDFThe BCL2 inhibitor venetoclax has established therapeutic roles in chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). As BCL2 is an important determinant of survival of both myeloid progenitor and B cells, we investigated whether clinical and molecular abnormalities arise in the myeloid compartment during long-term continuous venetoclax treatment of CLL in 89 patients (87 with relapsed/refractory CLL). Over a median follow-up of 75 (range 21-98) months, persistent cytopenias (≥1 of neutropenia, thrombocytopenia, anemia) lasting ≥4 months and unrelated to CLL occurred in 25 patients (28%).
View Article and Find Full Text PDFElectrons and ions trapped with electromagnetic fields have long served as important high-precision metrological instruments, and more recently have also been proposed as a platform for quantum information processing. Here we point out that these systems can also be used as highly sensitive detectors of passing charged particles, due to the combination of their extreme charge-to-mass ratio and low-noise quantum readout and control. In particular, these systems can be used to detect energy depositions many orders of magnitude below typical ionization scales.
View Article and Find Full Text PDFPurpose: In 2017, Veterans Health Administration (VA) launched a social marketing and training campaign to address harassment of women veterans at VA health care facilities. We assessed women veterans' experiences of harassment, reported perpetrators of harassment, and perceptions of VA in 2017 (before campaign launch) and 2018 (1 year after campaign implementation).
Methods: We administered surveys to women veterans attending primary care appointments (2017, n = 1,300; 2018, n = 1,711).
Breast Cancer Res Treat
August 2021
Purpose: Pregnancy-associated breast cancer (PABC) is defined as breast cancer diagnosed during the gestational period (gp-PABC) or in the first postpartum year (pp-PABC). Despite its infrequent occurrence, the incidence of PABC appears to be rising due to the increasing propensity for women to delay childbirth. We have established the first retrospective registry study of PABC in Ireland to examine specific clinicopathological characteristics, treatments, and maternal and foetal outcomes.
View Article and Find Full Text PDFNew drugs introduced to the market are privileged structures having affinities for biological targets implicated in human diseases and conditions. These new chemical entities (NCEs), particularly small molecules and antibody-drug conjugates, provide insight into molecular recognition and simultaneously function as leads for the design of future medicines. This review is part of a continuing series presenting the most likely process-scale synthetic approaches to 40 NCEs approved for the first time anywhere in the world in 2019.
View Article and Find Full Text PDFBackground: Motor vehicle (MVCs) and motorcycle crashes (MCCs) continue to be among the most prevalent mechanisms of trauma injury and mortality. We sought to identify specific populations and factors associated with MVCs and MCCs for local injury prevention efforts. A novel, yet easily performed, research method was utilized-a qualitative content analysis of text narratives describing each patient's cause of injury.
View Article and Find Full Text PDFKey insights: A: Addressing a complex problem like harassment in VA medical facilities requires committed, engaged collaboration at multiple levels of the organization. B: Timely feedback of initial research findings to operations partners enabled rapid and more responsive development of new programs and policies. C: Our research-clinical partnership has enabled us to pursue targeted change from the outset, while incorporating real-time findings from embedded researchers working to develop a comprehensive understanding of the problem.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic has resulted in radical changes in the delivery of healthcare worldwide. Our oncology service (at an Irish national cancer centre) rapidly transitioned to the use of telemedicine or virtual clinics (VC) to minimise potential risk of exposure to COVID-19 amongst an immunosuppressed, high-risk population. Our study aimed to evaluate the use of VC in this setting.
View Article and Find Full Text PDFBackground: Systemic anti-cancer treatment (SACT) can improve symptoms and survival in patients with incurable cancer but there may be harmful consequences. Information regarding the use of SACT at the end-of-life and its impact on patients has not been described in Ireland.
Aims: The study aimed to quantify and describe the use of SACT at end-of-life.