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Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, and end-diastolic diameter, and others, are used to assess cardiac function, their dependency on loading conditions somewhat limit their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include of the interaction between the ventricle and the aorta (ventriculo-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity. We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in mouse model of cardiac-restricted low levels TRAF2 overexpression that conferred cytoprotection in the heart. While previous studies reported that response to myocardial infraction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, lower aortic pressures and rate-pressure product, lower LV contractility and relaxation, and lower stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity. While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate a diminished cardiac function in these mice.

Computed Tomography (CT) scans help diagnose and triage life-threatening and time-sensitive emergency conditions, but most rural hospitals in British Columbia do not have access to a local CT scanner. We investigate how many transfers from a rural British Columbia hospital were for CT scans and describe the time delays to emergent CT imaging.This was a prospective cohort study, over a 1-year period, on all patients requiring a transfer from the Golden and District Hospital, located 247 km from the closest CT scanner. Data collection forms were completed prospectively and the main measurements included age, transport triage level, reason for transfer, referral hospital, transfer request time, and CT scan time. The time interval between the CT request and CT imaging was calculated and represents the 'delay to CT scan' interval.The study hospital received 8672 emergency department (ED) visits and 220 were transferred to referral centres (2.5%). 61% of all transfers received a CT scan. Transfers for time-sensitive emergencies took an average of 6 h 52 min. Patients with acute stroke experienced a 4 h 44 min time interval. Less urgent and non-urgent conditions entailed an even greater time delay.This study highlights that the lack of a rural CT scanner is associated with increased transfers and significant time delays. Improving access to CT scanners for rural communities may be one of the many steps in addressing healthcare disparities between rural and urban communities.RéSUMé: OBJECTIFS: La tomodensitométrie (TDM) aide à diagnostiquer et à trier les situations d'urgence qui mettent la vie en danger et pour lesquelles le temps est compté, mais la plupart des hôpitaux ruraux de la Colombie-Britannique n'ont pas accès à un tomodensitomètre local. Nous enquêtons sur le nombre de transferts d’un hôpital rural de la Colombie-Britannique pour des tomodensitogrammes et nous décrivons les délais pour l’imagerie tomographique émergente. MéTHODES: Il s'agit d'une étude de cohorte prospective, sur une période d'un an, sur tous les patients nécessitant un transfert de l'hôpital de Golden and district, situé à 247 km du scanner le plus proche. Les formulaires de collecte de données ont été remplis de manière prospective et les principales mesures comprenaient l'âge, le niveau de triage de transport, la raison du transfert, l'hôpital de référence, le temps de demande de transfert et le temps de tomodensitométrie. L’intervalle de temps entre la demande de tomodensitométrie et l’imagerie par tomodensitométrie a été calculé et représente l’intervalle « retard au scanner». RéSULTATS: L’hôpital d’étude a reçu 8 672 visites aux services d’urgence (SU) et 220 ont été transférés aux centres d’aiguillage (2,5%). 61% de tous les transferts ont fait l'objet d'un scanner. Les transferts pour les urgences sensibles au facteur temps ont pris en moyenne 6 h 52. Les patients ayant subi un accident vasculaire cérébral aigu ont connu un intervalle de temps de 4 h 44. Des conditions moins urgentes et non urgentes ont entraîné un délai encore plus long. CONCLUSIONS: Cette étude met en évidence que l'absence de tomodensitomètre en milieu rural est associée à une augmentation des transferts et à des retards importants. L’amélioration de l’accès aux tomodensitomètres pour les communautés rurales peut être l’une des nombreuses étapes pour remédier aux disparités en matière de soins de santé entre les communautés rurales et urbaines.

The purpose of our study was to determine if regular cardiopulmonary resuscitation (CPR) practise improved the quality of nurses' chest compressions in a rural hospital.The study was a prospective interventional trial measuring the effectiveness of brief, monthly CPR practice for rural nurses. The quality of nurses' chest compressions was measured before and after monthly practise with an interactive feedback device at the Golden and District Hospital, a rural facility in BC.All three components of high-quality CPR (depth, recoil and rate) improved significantly.Monthly practise of chest compressions with an interactive feedback device improved the quality and confidence of nurses' CPR skills. These results suggest that a higher frequency of CPR practice (than the minimum annual recertification) would improve both the quality and retention of CPR skills, specifically for low-volume rural hospitals.

Background ATG and post-transplant cyclophosphamide (PT-Cy) have been individually shown to be efficacious in reducing rates of GVHD in HLA matched and mismatched transplants. We adopted a combination regimen of ATG and PT-Cy for GVHD prophylaxis for matched unrelated donor (MUD) transplants in our centre to decrease the rates of acute and chronic GVHD. Patients and methods Pre-transplant conditioning consisted of iv Fludarabine (30mg/m2/day) for 4 days, iv Busulphan (3.2 mg/kg/day for 2 days), and low dose TBI (200cGy on day-1). GVHD prophylaxis was with Thymoglobulin 4.5mg/kg over 3 days (day-3 to -1), PT-Cy 50 mg/kg/day on days+3 and +4 and cyclosporine from day+5 (taper started by day+45 in patients without GVHD). The stem cell source was G-CSF stimulated peripheral blood stem cells (PBSC) in all patients. Overall survival (OS) and progression free survival (PFS) were calculated using Kaplan Meir method. Among variables included in Cox regression analysis to identify predictors of survival were age, pre-transplant remission status, occurrence of CMV infection, donor type (10/10 vs 9/10), and occurrence of acute or chronic GVHD. Results A total of 102 patients (median age 59y, range 22-74y) with high-risk hematological malignancies (AML-55, MDS-20, MPD-9, ALL-5, CML-4, lymphoma-6, CMML-3) were treated with this protocol. Unrelated donors were 9/10 matched in 26 patients, and the rest were 10/10 matched. At a median follow-up of 12 months (range 0.5 to 31 months), the 1year OS and PFS were 66.5% (95% CI -57% -76%) and 57.6% (95% CI 47.6% -67.6%) respectively. The 1year OS for 10/10 transplants was 72.3% (95%CI 61.7%- 82.9%), which was significantly higher than that for 9/10 transplants at 50% (95%CI 30.4%- 69.6%, p=0.016). The 1year PFS for 10/10 donor transplants was 65.5% (95% CI-54.3%- 76.7%) which was significantly higher than that for 9/10 transplants at 34.6% (95%CI 16%- 53.2%, p=0.004). The 9/10 matched patients had significantly higher relapses (hazard ratio 3.2, 95%CI 1.4-7.1, P=.005) than 10/10 matched patients. There were five graft failures (one primary and four secondary). The non-relapse mortality (NRM) was 17.6 %. The overall incidence of acute GVHD was 40% (grade 3-4 acute GVHD was seen in 14.8% patients). The overall incidence of chronic GVHD was 19.6% (moderate/severe NIH stage chronic GVHD was seen in 8.8% patients). The overall relapse rate was 23.3%. CMV re-activation was seen in 50 (49%) patients, and EBV re-activation in 20 (19.6%) patients, and 10 (9.8%) patients were diagnosed with post-transplant lympho-proliferative disorder (PTLD). In univariate analysis, adverse predictors of survival were a) persistent disease at the time of transplant, b) absence of chronic GVHD, and c) 9/10 donor type. In multivariable analysis, the only independent predictors of survival were a) persistent disease at time of transplant [hazard ratio 6.96, 95% CI 1.97-24.7, p=0.003], and b) donor type 9/10 vs 10/10 [HR 2.59, 95% CI 1.15-5.8, p=0.022]. Conclusion Our experience shows that PT-Cy and ATG can be combined for GVHD prophylaxis in MUD PBSCTs with low rates of Gr3-4 acute GVHD and chronic GVHD, and acceptable NRM and relapse rates. There were high rates of viral reactivation including PTLD. Figure. Figure. Disclosures Lipton: ARIAD: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding.

Although microglia have been implicated in nerve injury-induced neuropathic pain, the manner by which injured sensory neurons engage microglia remains unclear. We found that peripheral nerve injury induced de novo expression of colony-stimulating factor 1 (CSF1) in injured sensory neurons. CSF1 was transported to the spinal cord, where it targeted the microglial CSF1 receptor (CSF1R). Cre-mediated sensory neuron deletion of Csf1 completely prevented nerve injury-induced mechanical hypersensitivity and reduced microglial activation and proliferation. In contrast, intrathecal injection of CSF1 induced mechanical hypersensitivity and microglial proliferation. Nerve injury also upregulated CSF1 in motoneurons, where it was required for ventral horn microglial activation and proliferation. Downstream of CSF1R, we found that the microglial membrane adaptor protein DAP12 was required for both nerve injury- and intrathecal CSF1-induced upregulation of pain-related microglial genes and the ensuing pain, but not for microglial proliferation. Thus, both CSF1 and DAP12 are potential targets for the pharmacotherapy of neuropathic pain.

This study presents an acoustic comparison between New Zealand English (NZE) and Australian English (AE) citation‐form monophthongs and diphthongs. Formant frequencies were calculated and the data were labelled for vowel target position. Four main kinds of analysis were carried out: F1/F2 formant plots of monophthongs, onglides in vowels exemplified by HEED and WHO'D, formant trajectories of rising diphthongs, and formant trajectories of falling diphthongs. Consistent with other studies, we find the major differences in the NZE and AE vowel spaces are the centralizing and lowering of NZE HID and HOOD, and the raising of the NZE front and high vowels. The major difference in the diphthongs is the HERE/HAIR merger occurring in NZE but not AE. Contrary to other studies we find both HEED and WHO'D in NZE have long onglides and that the extent of these onglides is similar to those in AE. Proposals are included for a modification to the transcription system of NZE.

Eight classes of organic sulfur compounds, comprising 42 substances, were tested in vitro for activity against the yeast phase ofHistoplasma capsulatum Darling. Activity was found in the classes of thiols, thio acids, disulfides, and thiolsulfonates. The classes of sulfinates, sulfenamides, penicillamine analogs, and reaction products of thiols with aldehydes or ketones were unpromising. Tentative conclusions are drawn of structure-activity relations within classes as a guide to coupling of classes to form disulfides.

A number of compounds were screened for their effects on growth of the yeast cells ofHistoplasma capsulatum. Included were penicillin and related compounds, sulfhydryl inhibitors, various organic sulfur compounds recently synthesized for the first time, and compounds structurally related to the required metabolites, thiamine and cystine or cysteine. Cephalothin was the only one of the penicillin related compounds which inhibited growth. This occurred only when a high concentration (8.3 × 10−4 M) was used. Of the analogues of cystine tested, allylglycine had the greatest inhibitory effect on growth of the yeast cells in the synthetic medium, but it failed to inhibit growth in a complex medium containing peptones and plasma. Among the sulfhydryl inhibitors, the maleimides were the most effective, producing complete inhibition of growth in the peptone medium at 10µg/ml or less. At subinhibitory concentrations the cultures tended to become mycelial. The action of the maleimides was reversed by cystine over a range of concentrations. At low concentrations, some of the disulfide derivatives of thiamine stimulated growth equally as well as thiamine, but at concentrations of 100 to 150µg/ml, they completely inhibited growth. On the basis of results obtained to date, three classes of the new organic sulfur compounds being tested offer promise as sources of potentially useful chemotherapeutic agents. These classes, which differ widely in structure, are as follows: the benzyl decylaminoethyl disulfides, the acyl disulfides, and the trithiopercarbamates.