Innovation in immediate neonatal care: development of the Bedside Assessment, Stabilisation and Initial Cardiorespiratory Support (BASICS) trolley

OBJECTIVE: Babies receive oxygen through their umbilical cord while in the uterus and for a few minutes after birth. Currently, if the baby is not breathing well at birth, the cord is cut so as to transfer the newborn to a resuscitation unit. We sought to develop a mobile resuscitation trolley on which newly born babies can be resuscitated while still receiving oxygenated blood and the 'placental transfusion' through the umbilical cord. This would also prevent separation of the mother and baby in the first minutes after birth. DESIGN: Multidisciplinary iterative product development. SETTING: Clinical Engineering Department of a University Teaching Hospital. METHODS: Following an initial design meeting, a series of prototypes were developed. At each stage, the prototype was reviewed by a team of experts in the laboratory and in the hospital delivery suite to determine ease of use and fitness for purpose. A commercial company was identified to collaborate on the trolley's development and secure marking with the Conformite Europeenne mark, allowing the trolley to be introduced into clinical practice. RESULTS: The trolley is a small mobile resuscitation unit based on the concept of an overbed hospital table. It can be manoeuvred to within 50 cm of the mother's pelvis so that the umbilical cord can remain intact during resuscitation, irrespective of whether the baby is born naturally, by instrumental delivery or by caesarean section. Warmth for the newborn comes from a heated mattress and the trolley has the facility to provide suction, oxygen and air. CONCLUSIONS: This is the first mobile resuscitation device designed specifically to facilitate newborn resuscitation at the bedside and with an intact cord. The next step is to assess its safety, its acceptability to clinicians and parents, and to determine whether it allows resuscitation with an intact cord

Audiovisual integration in social evaluation

Our social evaluation of other people is influenced by their faces and their voices. However, rather little is known about how these channels combine in forming "first impressions." Over 5 experiments, we investigate the relative contributions of facial and vocal information for social judgments: dominance and trustworthiness. The experiments manipulate each of these sources of information within-person, combining faces and voices giving rise to different social attributions. We report that vocal pitch is a reliable source of information for judgments of dominance (Study 1), but not trustworthiness (Study 4). Faces and voices make reliable, but independent, contributions to social evaluation. However, voices have the larger influence in judgments of dominance (Study 2), whereas faces have the larger influence in judgments of trustworthiness (Study 5). The independent contribution of the 2 sources appears to be mandatory, as instructions to ignore 1 channel do not eliminate its influence (Study 3). Our results show that information contained in both the face and the voice contributes to first impression formation. This combination is, to some degree, outside conscious control, and the weighting of channel contribution varies according the trait being perceived. (PsycINFO Database Recor

What is the 'problem' that outreach work seeks to address and how might it be tackled? Seeking theory in a primary health prevention programme

<b>Background</b> Preventive approaches to health are disproportionately accessed by the more affluent and recent health improvement policy advocates the use of targeted preventive primary care to reduce risk factors in poorer individuals and communities. Outreach has become part of the health service response. Outreach has a long history of engaging those who do not otherwise access services. It has, however, been described as eclectic in its purpose, clientele and mode of practice; its effectiveness is unproven. Using a primary prevention programme in the UK as a case, this paper addresses two research questions: what are the perceived problems of non-engagement that outreach aims to address; and, what specific mechanisms of outreach are hypothesised to tackle these.<p></p> <b>Methods</b> Drawing on a wider programme evaluation, the study undertook qualitative interviews with strategically selected health-care professionals. The analysis was thematically guided by the concept of 'candidacy' which theorises the dynamic process through which services and individuals negotiate appropriate service use.<p></p> <b>Results</b> The study identified seven types of engagement 'problem' and corresponding solutions. These 'problems' lie on a continuum of complexity in terms of the challenges they present to primary care. Reasons for non-engagement are congruent with the concept of 'candidacy' but point to ways in which it can be expanded.<p></p> <b>Conclusions</b> The paper draws conclusions about the role of outreach in contributing to the implementation of inequalities focused primary prevention and identifies further research needed in the theoretical development of both outreach as an approach and candidacy as a conceptual framework

Maternally derived anti-helminth antibodies predict offspring survival in a wild mammal

The transfer of antibodies from mother to offspring provides crucial protection against infection to offspring during early life in humans and domestic and laboratory animals. However, few studies have tested the consequences of variation in maternal antibody transfer for offspring fitness in the wild. Further, separating the immunoprotective effects of antibodies from their association with nutritional resources provided by mothers is difficult. Here, we measured plasma levels of total and parasite-specific antibodies in neonatal (less than 10 days old) wild Soay sheep over 25 years to quantify variation in maternal antibody transfer and test its association with offspring survival. Maternal antibody transfer was predicted by maternal age and previous antibody responses, and was consistent within mothers across years. Neonatal total IgG antibody levels were positively related to early growth, suggesting they reflected nutritional transfer. Neonatal parasite-specific IgG levels positively predicted first-year survival, independent of lamb weight, total IgG levels and subsequent lamb parasite-specific antibody levels. This relationship was partly mediated via an indirect negative association with parasite burden. We show that among-female variation in maternal antibody transfer can have long-term effects on offspring growth, parasite burden and fitness in the wild, and is likely to impact naturally occurring host–parasite dynamics

Isolated thumb carpometacarpal joint dislocation: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Isolated thumb carpometacarpal dislocation is a rare injury pattern and the optimal treatment option is still controversial.</p> <p>Case Description</p> <p>We present a 27-year-old basketball player who underwent an isolated dorsal dislocation of the thumb carpometacarpal joint after a fall. The dislocation was successfully reduced by closed means but the joint was found to be grossly unstable. Due to inherent instability, repair of the ruptured dorsoradial ligament and joint capsule was performed.</p> <p>The ligament was detached from its proximal insertion into trapezium and subsequently stabilized via suture anchors. The torn capsule was repaired in an end-to-end fashion and immobilization of the joint was applied for 6 weeks.</p> <p>Results</p> <p>At 3-year follow up evaluation the patient was pain free and returned to his previous level of activity. No restriction of carpometacrpal movements or residual instability was noticed. Radiographic examination showed normal joint alignment and no signs of subluxation or early osteoarthritis.</p> <p>Conclusion</p> <p>Surgical stabilization of the dorsal capsuloligamentous complex may be considered the selected treatment option in isolated carpometacarpal joint dislocations, that remain unstable after closed reduction in young and high demand patients.</p> <p><b>Level of Clinical Evidence: </b>Level IV</p

Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice

<p>Abstract</p> <p>Background</p> <p>Spontaneous Regression/Complete Resistant (SR/CR) mice are resistant to cancer through a mechanism that is mediated entirely by leukocytes of innate immunity. Transfer of leukocytes from SR/CR mice can confer cancer resistance in wild-type (WT) recipients in both preventative and therapeutic settings. In the current studies, we investigated factors that may impact the efficacy and functionality of SR/CR donor leukocytes in recipients.</p> <p>Results</p> <p>In sex-mismatched transfers, functionality of female donor leukocytes was not affected in male recipients. In contrast, male donor leukocytes were greatly affected in the female recipients. In MHC-mismatches, recipients of different MHC backgrounds, or mice of different strains, showed a greater negative impact on donor leukocytes than sex-mismatches. The negative effects of sex-mismatch and MHC-mismatch on donor leukocytes were additive. Old donor leukocytes performed worse than young donor leukocytes in all settings including in young recipients. Young recipients were not able to revive the declining function of old donor leukocytes. However, the function of young donor leukocytes declined gradually in old recipients, suggesting that an aged environment may contain factors that are deleterious to cellular functions. The irradiation of donor leukocytes prior to transfers had a profound suppressive effect on donor leukocyte functions, possibly as a result of impaired transcription. The cryopreserving of donor leukocytes in liquid nitrogen had no apparent effect on donor leukocyte functions, except for a small loss of cell number after revival from freezing.</p> <p>Conclusion</p> <p>Despite the functional suppression of donor leukocytes in sex- and MHC-mismatched recipients, as well as old recipients, there was a therapeutic time period during the initial few weeks during which donor leukocytes were functional before their eventual rejection or functional decline. The eventual rejection of donor leukocytes will likely prevent donor leukocyte engraftment which would help minimize the risk of transfusion-associated graft-versus-host disease. Therefore, using leukocytes from healthy donors with high anti-cancer activity may be a feasible therapeutic concept for treating malignant diseases.</p

Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2.

Proteolysis-Targeting Chimeras (PROTACs) are heterobifunctional small-molecules that can promote the rapid and selective proteasome-mediated degradation of intracellular proteins through the recruitment of E3 ligase complexes to non-native protein substrates. The catalytic mechanism of action of PROTACs represents an exciting new modality in drug discovery that offers several potential advantages over traditional small-molecule inhibitors, including the potential to deliver pharmacodynamic (PD) efficacy which extends beyond the detectable pharmacokinetic (PK) presence of the PROTAC, driven by the synthesis rate of the protein. Herein we report the identification and development of PROTACs that selectively degrade Receptor-Interacting Serine/Threonine Protein Kinase 2 (RIPK2) and demonstrate in vivo degradation of endogenous RIPK2 in rats at low doses and extended PD that persists in the absence of detectable compound. This disconnect between PK and PD, when coupled with low nanomolar potency, offers the potential for low human doses and infrequent dosing regimens with PROTAC medicines