Reducing the risk of Sudden and Unexpected Death in Infancy (SUDI) is a priority for infant health care services across the globe. Medical knowledge of risk factors for SUDI are well understood and ...have been part of public health messaging in the UK since the 1990s. These include the ‘back to sleep’ campaign that focused on newborn sleep position, not over wrapping the infant and to avoid passive smoke. Whilst progress has been made in reducing SUDI deaths worldwide, there are some infants who remain at high risk. This article adopts a sociomaterial lens to address the potential for material-based interventions to support messages to be tailored in culturally appropriate ways that do not negate parenting knowledge and practices. We focus on the proliferation of the ‘baby box’ as an example of material appropriation and consider the risks and the potentials for this object as a participant in parenting practices.
Children and young people who live away from birth families (through adoption or being in care) need an understanding of their life story, including reasons for removal from birth family to process ...what has happened to them and to develop a secure identity. We report data produced with care experienced children and young people using a creative sandboxing method capturing hopes and fears for conversations about care in sand scenes. The themes presented emphasise the need for care‐experienced children and young people to be supported to engage in ‘difficult conversations’ about their lives in warm, open and responsive ways.
Background Few studies have investigated the effectiveness of enhanced recovery pathways (ERP) for lung resection. This study estimates the impact of an ERP for lobectomy on duration of stay, ...complications, and readmissions. Methods Patients undergoing open lobectomy were identified from an OR database between 2011 and 2013. Beginning September 2012, all patients were managed according to a 4-day multidisciplinary ERP with written daily patient education treatment plans, multimodal analgesia, early diet, structured mobilization and standardized drain management. Pre-pathway (PRE) and post-pathway (POST) patients were compared in terms of duration of stay, complications, and readmissions. Results We identified 234 patients (PRE, 127; POST, 107). Groups were similar with respect to age, gender, American Society of Anesthesiologists score, and baseline pulmonary function. Compared with the PRE group, the POST group had decreased duration of stay (median, 6 interquartile range (IQR), 5–7 vs 7 6–10 days; P < .05), total complications (40 37% vs 64 50%; P < .05), urinary tract infections (3 3% vs 15 12%; P < .05), and chest tube duration (median, 4 IQR, 3–6 vs 5 4–7 days; P < .05), with no difference in readmissions (7 7% vs 6 5%; P < .05) or chest tube reinsertion (4 4% vs 6 5%; P < .05). Decreased duration of stay was driven by patients without complications (median, 5 IQR, 4–6 vs 6 5–7 days; P < .05). Conclusion Implementation of a multimodal ERP for lobectomy was associated with decreased duration of stay and complications with no difference in readmissions.
This book challenges the ways we experience, think about, and interact with children described as having profound and multiple learning disabilities (PMLD). Contrary to received wisdom, the book ...starts from the premise that traditional psychological approaches operating in the "PMLD field" are overly reductive and constrain our abilities to listen to and learn from children with PMLD. This in turn runs the risk of maintaining exclusionary practices such as segregated education, where such practices are predicated upon the notion that some children are too disabled to participate in mainstream life. To address the situation the authors explore new terrain in three areas: theory, research and practice. The authors draw from phenomenological notions of embodied consciousness and introduce how this gives rise to novel ways of understanding the agency of children with PMLD. This critique leads to examination of interpersonal methodology as a means to access the experiences of children with PMLD, which in turn culminates in a research project examining how inclusive education could support learning for a young boy with PMLD.
Graft-versus-host disease (GVHD) is a T cell-mediated inflammatory disorder that arises from allogeneic haematopoietic stem cell transplantation and is often fatal. The P2X7 receptor is an ...extracellular adenosine 5′-triphosphate-gated cation channel expressed on immune cells. Blockade of this receptor with small molecule inhibitors impairs GVHD in a humanised mouse model. A species-specific blocking monoclonal antibody (mAb) (clone L4) for human P2X7 is available, affording the opportunity to determine whether donor (human) P2X7 contributes to the development of GVHD in humanised mice. Using flow cytometric assays of human RPMI 8266 and murine J774 cells, this study confirmed that this mAb bound and impaired human P2X7. Furthermore, this mAb prevented the loss of human regulatory T cells (hTregs) and natural killer (hNK) T cells in vitro. NOD-scid IL2Rγnull mice were injected with 10 × 106 human peripheral blood mononuclear cells (Day 0) and an anti-hP2X7 or control mAb (100 μg i.p. per mouse, Days 0, 2, 4, 6, and 8). The anti-hP2X7 mAb increased hTregs and hNK cells at Day 21. Moreover, anti-hP2X7 mAb-treatment reduced clinical and histological GVHD in the liver and lung compared to the control treatment at disease endpoint. hTregs, hNK, and hNK T cell proportions were increased, and human T helper 17 cell proportions were decreased at endpoint. These studies indicate that blockade of human (donor) P2X7 reduces GVHD development in humanised mice, providing the first direct evidence of a role for donor P2X7 in GVHD.
The P2X7 receptor is a trimeric ligand-gated cation channel activated by extracellular adenosine 5'-triphosphate. The study of animals has greatly advanced the investigation of P2X7 and helped to ...establish the numerous physiological and pathophysiological roles of this receptor in human health and disease. Following a short overview of the P2X7 distribution, roles and functional properties, this article discusses how animal models have contributed to the generation of P2X7-specific antibodies and nanobodies (including biologics), recombinant receptors and radioligands to study P2X7 as well as to the pharmacokinetic testing of P2X7 antagonists. This article then outlines how mouse and rat models have been used to study P2X7. These sections include discussions on preclinical disease models, polymorphic P2X7 variants, P2X7 knockout mice (including bone marrow chimeras and conditional knockouts), P2X7 reporter mice, humanized P2X7 mice and P2X7 knockout rats. Finally, this article reviews the limited number of studies involving guinea pigs, rabbits, monkeys (rhesus macaques), dogs, cats, zebrafish, and other fish species (seabream, ayu sweetfish, rainbow trout and Japanese flounder) to study P2X7.
Allogeneic haematopoietic stem cell transplantation (HSCT) leads to the establishment of graft-versus-leukaemia (GVL) immunity, but in many cases also results in the development of graft-versus-host ...disease (GVHD). This study aimed to determine if P2X7 antagonism using Brilliant Blue G (BBG) could improve the beneficial effects of post-transplant cyclophosphamide (PTCy) in a humanised mouse model of GVHD, without comprising GVL immunity. NOD.Cg-
(NSG) mice were injected with human peripheral blood mononuclear cells (PBMCs) (Day 0), then with cyclophosphamide (33 mg/kg) on Days 3 and 4, and with BBG (50 mg/kg) (or saline) on Days 0-10. PTCy with BBG reduced clinical GVHD development like that of PTCy alone. However, histological analysis revealed that the combined treatment reduced liver GVHD to a greater extent than PTCy alone. Flow cytometric analyses revealed that this reduction in liver GVHD by PTCy with BBG corresponded to an increase in human splenic CD39
Tregs and a decrease in human serum interferon-γ concentrations. In additional experiments, humanised NSG mice, following combined treatment, were injected with human THP-1 acute myeloid leukaemia cells on Day 14. Flow cytometric analyses of liver CD33
THP-1 cells showed that PTCy with BBG did not mitigate GVL immunity. In summary, PTCy combined with BBG can reduce GVHD without compromising GVL immunity. Future studies investigating P2X7 antagonism in combination with PTCy may lead to the development of novel treatments that more effectively reduce GVHD in allogeneic HSCT patients without promoting leukaemia relapse.
Purpose Enhanced recovery pathways (ERP) decrease morbidity and duration of stay after colorectal surgery. There is little information about their role in complex procedures, such as esophagectomy. ...The purpose of this study was to determine the impact of an ERP on duration of stay, complications, and readmissions after esophagectomy. Methods Patients undergoing esophagectomy for cancer or high-grade dysplasia from June 2009 to December 2011 were identified from a prospectively maintained database. Beginning in June 2010, all patients were enrolled in a 7-day multidisciplinary ERP including written patient education with daily treatment plan, indications for intensive care admission, early structured mobilization, and diet and drain management. Short-term (30-day) outcomes were compared for patients undergoing esophagectomy pre- and post-pathway. Data are expressed as median values interquartile range. Results We identified 106 patients; 47 underwent esophagectomy before ERP implementation and 59 after. Patients were similar with respect to age, gender, diagnosis, and operative time. Hospital stay was shorter in the ERP group (8 7–17 vs 10 9–17 days; P = .01). There were no differences in rates of complications (59% vs 62%) or readmissions (6% vs 5%). Conclusion Implementation of a multidisciplinary ERP for esophagectomy was associated with decreased duration of stay, without an increase in complications or readmissions.
The ectonucleotidases CD39 and CD73 are present on immune cells and play important roles in cancer progression by suppressing antitumour immunity. As such, CD39 and CD73 on peripheral blood ...mononuclear cells (PBMCs) are emerging as potential biomarkers to predict disease outcomes and treatment responses in cancer patients. This study aimed to examine T and B cells, including CD39 and CD73 expressing subsets, by flow cytometry in PBMCs from 28 patients with head and neck squamous cell carcinoma (HNSCC) and to assess the correlation with the treatment modality, human papillomavirus (HPV) status, and relapse-free survival (RFS). The PBMCs were examined pre-, mid-, and post-radiotherapy with concurrent cisplatin chemotherapy or anti-epidermal growth factor receptor antibody (cetuximab) therapy. Combination radiotherapy caused changes to T and B cell populations, including CD39 and CD73 expressing subsets, but no such differences were observed between concurrent chemotherapy and cetuximab. Pretreatment PBMCs from HPV+ patients contained increased proportions of CD39−CD73−CD4+ T cells and reduced proportions of CD39−/+CD73+CD4+ T cells compared to the equivalent cells from HPV− patients. Notably, the pretreatment CD4+:CD8+ T cell ratios and CD39+CD73+CD19+ B cell proportions below the respective cohort medians corresponded with an improved RFS. Collectively, this study supports the notion that CD39 and CD73 may contribute to disease outcomes in HNSCC patients and may assist as biomarkers, either alone or as part of immune signatures, in HNSCC. Further studies of CD39 and CD73 on PBMCs from larger cohorts of HNSCC patients are warranted.
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