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Background A 21 month Macmillan Funded Programme has been undertaken to transform weekend and bank holiday Specialist Palliative Care (SPC) provision in Salford. This has tested the proposed APM model, increasing the level of 7 day working staffing from the minimum to Level 1 with elements of Level 2. Method In addition to the established Senior Clinical Nurse Specialist (SCNS) rotas in hospital and community, new Advanced Clinical Nurse Specialists (ACNS) with enhanced clinical skills have delivered senior SPC face to face reviews across care settings. For 50% of weekends, medical consultant face to face review has also been available. Outcome measures have been developed. Results Over 600 complex patients have had senior SPC review at the weekend, across care settings in the initial 10 months. Average hospital weekend referrals have increased by 37% (from 16.9 to 23.1) with improvement in hospital weekend response times (81.2% Vs 69.6% seen within 24hrs). Reduction in symptom and Psychosocial scores has been demonstrated, with patients and carers feel well supported by the responsiveness of the teams. Increase in documented advance care plans from 26% to 67%. Over 70 GP home visits prevented by the community Urgent Response service in 6 months. Demonstrated avoidance of inappropriate hospital admissions and the trend towards reduction in hospital length of stay equate to potential annualised saving of 1,360 bed days or 3.7 beds per year. Improved career pathway for CNSs and support for SCNSs by ACNSs. ACNSs have delivered service improvement projects: One Stop COPD Clinic Emergency Assessment Unit and Emergency Department in–reach A pioneering ‘10 in 10’ education programme ‘Urgent Response’ community work Support to GPs to improve GSF meetings Conclusion This model has demonstrated patient, carer, staff and cost benefits as well as addressing issues with inequity of service delivery and capacity across care settings.

The deleterious effects of hydrocephalus, a disorder that primarily affects children, include reactive astrocytosis, microgliosis and inflammatory responses; however, the roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. Therefore we have examined neuroinflammation at both the cellular and the molecular levels in an experimental model of neonatal obstructive hydrocephalus. On post-natal day 1, rats received an intracisternal injection of kaolin to induce hydrocephalus; control animals received saline injections. Prior to sacrifice on post-natal day 22, animals underwent magnetic resonance imaging to quantify ventricular enlargement, and the parietal cortex was harvested for analysis. Immunohistochemistry and light microscopy were performed on 5 hydrocephalic and 5 control animals; another set of 5 hydrocephalic and 5 control animals underwent molecular testing with Western blots and a gene microarray. Scoring of immunoreactivity on a 4-point ranking scale for GFAP and Iba-1 demonstrated an increase in reactive astrocytes and reactive microglia respectively in the hydrocephalic animals compared to controls (2.90±0.11 vs. 0.28±0.26; 2.91±0.11 vs. 0.58±0.23, respectively). Western blots confirmed these results. Microarray analysis identified significant (1.5-fold) changes in 1729 of 33,951 genes, including 26 genes out of 185 genes (26/185) in the cytokine-cytokine receptor interaction pathway, antigen processing and presentation pathways (15/66), and the apoptosis pathway (10/69). Collectively, these results demonstrate alterations in normal physiology and an up-regulation of the inflammatory response. These findings lead to a better understanding of neonatal hydrocephalus and begin to form a baseline for future treatments that may reverse these effects.

Beatrice’s outburst in this epigraph pithily incorporates the thematic triad at the heart of this study—masculinity, friendship, and violence— and even glances at medical discourse, which binds them together.2 These lines, and the larger passage from which they come, invite questions about the proposed correlation between manhood and violence, and the repercussions this equation has on men’s foundational relationships: in a culture privileging male-male homosocial amity as fervently as in early modern England, how could one friend contemplate challenging another friend to a duel, as happens with relative frequency in plays of the time? And once they have reached that level of emotional intensity, what determines whether they can ever return to or even improve upon their previous state of friendship, or whether one will kill the other? How, in short, might we re-read early modern friendship in such a way that violence becomes, at least upon occasion, a necessary ingredient for preserving that friendship rather than a purely literary invention introduced in order to intensify the dramatic situation in such plays as John Fletcher and William Shakespeare’s The Two Noble Kinsmen and Francis Beaumont and John Fletcher’s The Maid’s Tragedy?3

Background Hydrocephalus causes reactive astrocytosis and microgliosis throughout the brain but the global response of proinflammatory cytokines is not known. Thus we sought to characterize common inflammatory markers in a neonatal model of obstructive hydrocephalus. Our main hypothesis was that neuroinflammation would progress in neonatal hydrocephalus proportional to ventriculomegaly. In addition, the long-standing uncertainty about the possible global inflammatory effects of kaolin could also be addressed.

Background Previous studies in aging animals have shown that amyloid-beta protein (Aβ) accumulates and its transporters, low-density lipoprotein receptor-related protein-1 (LRP-1) and the receptor for advanced glycation end products (RAGE) are impaired during hydrocephalus. Furthermore, correlations between astrocytes and Aβ have been found in human cases of normal pressure hydrocephalus (NPH) and Alzheimer's disease (AD). Because hydrocephalus occurs frequently in children, we evaluated the expression of Aβ and its transporters and reactive astrocytosis in animals with neonatal hydrocephalus. Methods Hydrocephalus was induced in neonatal rats by intracisternal kaolin injections on post-natal day one, and severe ventriculomegaly developed over a three week period. MRI was performed on post-kaolin days 10 and 21 to document ventriculomegaly. Animals were sacrificed on post-kaolin day 21. For an age-related comparison, tissue was used from previous studies when hydrocephalus was induced in a group of adult animals at either 6 months or 12 months of age. Tissue was processed for immunohistochemistry to visualize LRP-1, RAGE, Aβ, and glial fibrillary acidic protein (GFAP) and with quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) to quantify expression of LRP-1, RAGE, and GFAP. Results When 21-day post-kaolin neonatal hydrocephalic animals were compared to adult (6–12 month old) hydrocephalic animals, immunohistochemistry demonstrated levels of Aβ, RAGE, and LRP-1 that were substantially lower in the younger animals; in contrast, GFAP levels were elevated in both young and old hydrocephalic animals. When the neonatal hydrocephalic animals were compared to age-matched controls, qRT-PCR demonstrated no significant changes in Aβ, LRP-1 and RAGE. However, immunohistochemistry showed very small increases or decreases in individual proteins. Furthermore, qRT-PCR indicated statistically significant increases in GFAP. Conclusion Neonatal rats with and without hydrocephalus had low expression of Aβ and its transporters when compared to adult rats with hydrocephalus. No statistical differences were observed in Aβ and its transporters between the control and hydrocephalic neonatal animals.

Address: 1Division of Pediatric Neurosurgery, 100 North Medical Drive, Suite 1475, Salt Lake City, UT 84113, USA, 2Department of Neurosurgery (Anatomy and Cell Biology), Wayne State University, 550 East Canfield St., Lande MRB 048, Detroit, MI 48201, USA, 3Neurosurgical Department, International Neuroscience Institute Hannover, Alexis-Carrel-Str. 4, Hannover, 30625, Germany, 4Department of Neurosurgery, Stanford University, 300 Pasteur Dr. Rm. 155, Palo Alto, CA 94304, USA and 5Department of Neurosurgery, Rhode Island Hospital and, Brown University, 593 Eddy Street, Providence, RI 02903, USA