Agricultural margins could enhance landscape connectivity for pollinating insects across the Central Valley of California, U.S.A.

One of the defining features of the Anthropocene is eroding ecosystem services, decreases in biodiversity, and overall reductions in the abundance of once-common organisms, including many insects that play innumerable roles in natural communities and agricultural systems that support human society. It is now clear that the preservation of insects cannot rely solely on the legal protection of natural areas far removed from the densest areas of human habitation. Instead, a critical challenge moving forward is to intelligently manage areas that include intensively farmed landscapes, such as the Central Valley of California. Here we attempt to meet this challenge with a tool for modeling landscape connectivity for insects (with pollinators in particular in mind) that builds on available information including lethality of pesticides and expert opinion on insect movement. Despite the massive fragmentation of the Central Valley, we find that connectivity is possible, especially utilizing the restoration or improvement of agricultural margins, which (in their summed area) exceed natural areas. Our modeling approach is flexible and can be used to address a wide range of questions regarding both changes in land cover as well as changes in pesticide application rates. Finally, we highlight key steps that could be taken moving forward and the great many knowledge gaps that could be addressed in the field to improve future iterations of our modeling approach.

Notch protection against apoptosis in T-ALL cells mediated by GIMAP5.

Recent studies have highlighted the role of Notch signalling in the development of T cell acute lymphoblasic leukaemia (T-ALL). Over-expression of Notch3 and gain of function mutations in the Notch1 gene have been reported. The aims of this study were to determine the effect of Notch signalling on apoptosis in human T-ALL cell lines and to identify targets of Notch signalling that may mediate this effect. Functional studies showed that inhibition of Notch signalling using gamma secretase inhibitors promoted glucocorticoid-induced apoptosis in cells carrying gain of function mutations in Notch1. Moreover, ectopic expression of constitutively activated Notch provided protection against glucocorticoid-induced apoptosis, indicating that signalling via Notch may also contribute to the development of T-ALL by conferring resistance to apoptosis. Microarray analysis revealed that GIMAP5, a gene coding for an anti-apoptotic intracellular protein, is upregulated by Notch in T-ALL cell lines. Knockdown of GIMAP5 expression using siRNA promoted glucocorticoid-induced apoptosis in T-ALL cells carrying gain of function mutations in Notch1 and in T-ALL cells engineered to express ectopic constitutively activated Notch indicating that Notch signalling protects T-ALL cells from apoptosis by upregulating the expression of GIMAP5.

Identification of novel Notch target genes in T cell leukaemia.

BACKGROUND: Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL) cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. RESULTS: RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone) or vectors containing constitutively active forms of Notch (N1DeltaE or N3DeltaE), and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1). CONCLUSION: The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

Introduction of an extended care paramedic model in New Zealand.

OBJECTIVES: The first extended care paramedic (ECP) model of care in New Zealand was introduced in the Kapiti region, north of Wellington in 2009. The ECP model aimed to increase the proportion of patients presenting to the ambulance service who could be treated in the community. This study evaluated the first 1000 patients seen by ECPs. METHODS: The first 1000 presentations attended by ECPs were examined to determine the proportions of patients transported to the ED and treated in the community. For patients treated in the community we determined the number presenting to the ED within 7 days of ECP attendance. RESULTS: A total of 797 patients (mean age 62 years) had 1000 clinical presentations. In 59% the patient was treated either at home or in the local community, with 40% transported to the ED. Within the same region and time period 74% of patients attended by standard paramedics were transported to the ED. The rate of ECP transport to the ED differed significantly by clinical condition, with 71% of cardiac presentations versus 19% of patients with spinal problems taken to the ED. In 31 cases (5%) where the patient had been managed in the community there was an acute ED presentation within 7 days. CONCLUSION: We observed that ECPs have significant potential to reduce hospital ED attendances by treating more patients in the community, and this is associated with a low rate of subsequent ED presentations. Prioritisation of dispatch of ECPs to particular types of patients might be useful in maximising this reduction.

Patient satisfaction and outcome using emergency care practitioners in New Zealand.

OBJECTIVE: A patient satisfaction survey was undertaken in the Kapiti District of the Wellington Region to ascertain patients' experience and opinions of New Zealand's first extended care paramedic (ECP) service before consideration is given to extending it to other locations within the region. Patient outcomes were also analysed for 1 week following ECP care. METHODS: One hundred patients, 50 attended by ECPs and 50 by standard emergency ambulance service paramedics, were interviewed by an independent assessor, either in person or by phone according to patient preference. The questionnaire was aimed at comparing the experience of both groups of patients, dividing them into those treated at home and those transferred to the ED. ED and general practice records were then reviewed to determine whether the ECP-treated patients attended either facility within 7 days and why. RESULTS: Patients were very satisfied with their experience of both groups of paramedics but expressed a clear desire to be treated at home if possible. Of the 50 ECP-treated patients, 11 were transferred directly to the ED. Only one clinical complication arose over the next 7 days in those treated in the community: a seizure in a patient with refractory epilepsy. CONCLUSION: The avoidance of unnecessary transfers to hospital is beneficial to patients, the ambulance service and the ED. This study demonstrates that patients are very satisfied with their assessment and treatment by ECPs, endorsing the proposal that the scheme should be extended across the Wellington Region, and perhaps New Zealand.

Outcomes from out-of-hospital cardiac arrest in the Wellington region of New Zealand. Does use of the Fire Service make a difference?

AIMS: Survival from community cardiac arrest in the Wellington region was analysed and compared with similar data reported nationally and internationally. In particular, the impact of a dual fire and ambulance service response was studied. METHOD: A retrospective comparative study was undertaken of out-of-hospital cardiac arrests in the Wellington region between 1 July 2007 and 31 December 2009. Data was collected from Wellington Free Ambulance and hospital records in accordance with the Utstein template. The New Zealand Fire Service provided details of firefighter attendance and timings. The primary outcome measure was survival to hospital discharge. RESULTS: Overall survival to hospital discharge was 11% (37/339) whilst survival from initial ventricular fibrillation or tachycardia (VF/VT) was 21% (34/161). Initial VF/VT was more common in witnessed than unwitnessed arrests (57% v. 35%, p=0.001) and this mirrored survival in these groups (15% vs 6%, p=0.01). Survival to hospital discharge was also associated with younger age and shorter emergency service response time. Bystanders attempted CPR in 55% and the fire service in 50% but neither intervention influenced outcome. Although, when activated, the fire service arrived on average 1-2 minutes ahead of the ambulance, the dual response did not influence survival to hospital admission or discharge. CONCLUSION: Survival from out-of-hospital cardiac arrest in Wellington is similar to that of other New Zealand cities and better than that reported from several large centres overseas. The combined fire and ambulance response was not shown to have any beneficial impact on survival over and above that achieved by the ambulance service alone. System changes are proposed to try and improve survival from community cardiac arrest in Wellington.

Survival from out-of-hospital cardiac arrest in New Zealand following the 2005 resuscitation guideline changes.

AIMS: The effect of cardiopulmonary resuscitation guideline changes on out-of-hospital survival rates and defibrillation efficacy was investigated. The guideline changes were those recommended by the International Liaison Committee on Resuscitation in 2005. METHODS: A retrospective comparative study was undertaken of out-of-hospital cardiac arrests in the Wellington region. The effect of guideline changes between the periods of 1st July 2005-30th June 2006 and 1st June 2007-31st May 2008 was examined. Data was collected from Wellington Free Ambulance and hospital records in accordance with the Utstein template. The primary outcome measure was survival to hospital discharge. Additional end points included individual shock success, return of spontaneous circulation (ROSC) and survival to hospital admission. RESULTS: There was no significant increase in survival to hospital discharge with 11% (18/162) pre-change and 12% (20/170) post-change (p=0.5). First-shock efficacy decreased from 68% (65/96) to 62% (57/92) (p=0.75). Second shock efficacy decreased from 47% (14/30) to 27% (9/33) (p=0.12). The proportion of patients with ROSC increased from 34% (55/162) to 42% (72/170) (p=0.07, Chi squared). The proportion surviving to hospital increased significantly from 22% (36/162) to 36% (61/170) (p=0.006). Withdrawal of atropine in 2005 had no adverse effect on the outcome. CONCLUSION: This study suggests that in the Wellington Region of New Zealand, the new guidelines have improved survival to hospital but not to discharge. Whilst the guideline changes have resulted in a trend towards decreased shock success rates, ROSC and survival to hospital admission have both increased.