Oconnorbland2819

al learning. Lack of a sense of belongingness and self-motivation to learn, and perceived fear of doing errors were some of the demotivating factors. Lack of resources to facilitate need-based training, staff shortages, workload and inconsistencies between theory and practice were other key challenges in the CLE. Understanding the challenges faced by students in clinical practice can help overcome the barriers leading to development of competent and confident nurses and midwives.

International evidence-based guidelines advise traditional Falls Risk Assessment Tools (FRATs) should not be routinely used to predict the risk of a patient falling in hospital. However, disinvestment from existing services can be challenging. This study applied evidence-based approaches to education design to implement best practice guidelines.

Mixed methods using questionnaires to evaluate health professionals' knowledge of evidence-based falls risk assessment and mitigation, followed by semi-structured interviews with individual health professionals.

Five Australian hospitals.

There were two cohorts per hospital; Cohort 1 (C1) comprised 10 clinical leaders from nursing and allied health professions. Cohort 2 (C2) included clinicians involved in routine hospital falls screening and prevention.

46 clinical leaders received a 3-h high quality education workshop on the latest evidence in hospital falls risk assessment and how to implement a new falls screening and management tool. They were also taugevidence-based hospital falls screening tool to help mitigate risk. An abridged version of the workshop did not result in long lasting effects. Education is an important element aiding disinvestment from non-evidence-based services, and implementation of clinical guidelines.Following the clinical success of immunotherapeutic antibodies, bispecific antibodies for cytotoxic effector cell redirection, tumor-targeted immunomodulation and dual immunomodulation, have received particular attentions. Here, we developed a novel bispecific antibody platform, termed Antibody-Like Cell Engager (ALiCE), wherein the Fc domain of each heavy chain of immunoglobulin G (IgG) is replaced by the VH and VL domains of an IgG specific to a second antigen while retaining the N-terminal Fab of the parent antibody. Because of specific interactions between the substituted VH and VL domains, the C-terminal stem Fv enables ALiCE to assemble autonomously into hetero-tetramers, thus simultaneously binding to two distinct antigens but with different avidities. This design strategy was used to generate ACE-05 (two anti-PD-L1 Fab × anti-CD3 Fv) and ACE-31 (two anti-CD3 Fab × anti-PD-L1 Fv), both of which bound PD-L1 and CD3. However, ACE-05 was more effective than ACE-31 in reducing off-target toxicity caused by the indiscriminate activation of T cells. Moreover, in cell-based assays and PBMC-reconstituted humanized mice harboring human non-small-cell lung cancer tumors, ACE-05 showed marked antitumor efficacy, causing complete tumor regression at a dose of 0.05 mg/kg body weight. The dual roles of ACE-05 in immune checkpoint inhibition and T-cell redirection, coupled with reduced off-target toxicity, suggest that ACE-05 may be a promising anti-cancer therapeutic agent. Moreover, the bispecific ALiCE platform can be further used for tumor-targeted or multiple immunomodulation applications.Triggerable nanocarriers have the potential to significantly improve the therapeutic index of existing anticancer agents. They allow for highly localised delivery and release of therapeutic cargos, reducing off-target toxicity and increasing anti-tumour activity. Liposomes may be engineered to respond to an externally applied stimulus such as focused ultrasound (FUS). Here, we report the first co-delivery of SN-38 (irinotecan's super-active metabolite) and carboplatin, using an MRI-visible thermosensitive liposome (iTSL). Sunitinib cost MR contrast enhancement was achieved by the incorporation of a gadolinium lipid conjugate in the liposome bilayer along with a dye-labelled lipid for near infrared fluorescence bioimaging. The resulting iTSL were successfully loaded with SN-38 in the lipid bilayer and carboplatin in the aqueous core - allowing co-delivery of both. The iTSL demonstrated both thermosensitivity and MR-imageability. In addition, they showed effective local targeted co-delivery of carboplatin and SN-38 after triggered release with brief FUS treatments. A single dosage induced significant improvement of anti-tumour activity (over either the free drugs or the iTSL without FUS-activation) in triple negative breast cancer xenografts tumours in mice.Pulmonary fibrosis is a rapidly progressive and fatal fibrotic lung disease with high mortality and morbidity. However, pulmonary fibrosis therapy in the clinic has been limited by poor selectivity and inefficiency of drug delivery to fibroblasts. Herein, a clodronate (CLD)-loaded liposome and fibroblast-derived exosome (EL-CLD) hybrid drug delivery system with non-specific phagocytosis inhibition and fibroblast homing properties, was designed for the treatment of pulmonary fibrosis. EL-CLD effectively depleted Kupffer cells via apoptosis by passive targeting after intravenous injection, and thus significantly reduced accumulation in the liver. Notably, the EL-CLD hybrid system preferentially accumulated in the fibrotic lung, and significantly increased penetration inside pulmonary fibrotic tissue by targeted delivery due to the specific affinity for fibroblasts of the homologous exosome. Nintedanib (NIN), an anti-fibrotic agent used to treat pulmonary fibrosis, was loaded in the EL-CLD system, and achieved a remarkable improvement in curative effects. The enhanced therapeutic efficacy of NIN was a result of enhanced pulmonary fibrotic tissue accumulation and delivery, combined with a diminished macrophage-induced inflammatory response. Hence, the EL-CLD hybrid system acts as an efficient carrier for pulmonary anti-fibrotic drug delivery and should be developed as an efficient fibroblast specific therapy.The energy absorbed into tissues is known as the specific energy absorption (SAR) which is dependent on conductivity of the tissue. We calculated cytoplasmic conductivity of human red blood cell (HRBC) using the intracellular ionic concentrations and the Debye-Hückel-Onsager relation. The overall concentration is determined by cell volume and cell water content. The calculated HRBC conductivity at 25 o C was σc,25 = 0.5566 ± 0.0146 S m-1, ±SE). It is exponentially related to temperature Q10 ≈ 1.866. At 37 o C, the calculated SAR value is 1.6 W kg-1 using a linear temperature compensation of conductivity. However, if using a biologically realistic non-linear temperature compensated conductivity, the SAR is ≈ 2.62 ± 0.05 W kg-1. The relationship between SAR and temperature increase is not straightforward. Since there is a wide variance in cellular ionic and water perfusion rates more tissue-specific SAR limits which consider temperature-related factors would be valuable.