Effect of intraoperative constant rate infusion of lidocaine on short-term survival of dogs with septic peritonitis: 75 cases (2007-2011)

OBJECTIVE To investigate whether intraoperative administration of a lidocaine infusion to dogs with septic peritonitis was associated with short-term (48 hours) survival after surgery. DESIGN Retrospective case series. ANIMALS 75 dogs with septic peritonitis. PROCEDURES Medical records of dogs with septic peritonitis that underwent laparotomy between January 2007 and December 2011 at the Royal Veterinary College were reviewed. Select variables during the preoperative, intraoperative, and postoperative periods and short-term survival after surgery were compared between dogs that received an opioid only (group O; n = 33) and dogs that received lidocaine (50 \u3bcg/kg/min [22.7 \u3bcg/kg/min], IV; group L; 42) in addition to an opioid during surgery. RESULTS The proportion of dogs that survived for 48 hours after surgery was significantly greater for group L (35/42) than for group O (20/33). Intraoperative infusion of lidocaine increased the odds of short-term survival (OR, 8.77; 95% CI, 1.94 to 39.57). No significant differences were observed between the 2 treatment groups for variables assessed during the preoperative and postoperative periods. During the intraoperative period, more dogs in group L received an IV bolus of a synthetic colloid than did dogs in group O, but the number of IV boluses administered was not associated with short-term survival. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IV infusion of lidocaine might improve the short-term survival of dogs with septic peritonitis. Prospective clinical trials are necessary to determine the efficacy of lidocaine as a supportive treatment for dogs with septic peritonitis

One-step volumetric additive manufacturing of complex polymer structures.

Two limitations of additive manufacturing methods that arise from layer-based fabrication are slow speed and geometric constraints (which include poor surface quality). Both limitations are overcome in the work reported here, introducing a new volumetric additive fabrication paradigm that produces photopolymer structures with complex nonperiodic three-dimensional geometries on a time scale of seconds. We implement this approach using holographic patterning of light fields, demonstrate the fabrication of a variety of structures, and study the properties of the light patterns and photosensitive resins required for this fabrication approach. The results indicate that low-absorbing resins containing ~0.1% photoinitiator, illuminated at modest powers (~10 to 100 mW), may be successfully used to build full structures in ~1 to 10 s

Cohomology for infinitesimal unipotent algebraic and quantum groups

In this paper we study the structure of cohomology spaces for the Frobenius kernels of unipotent and parabolic algebraic group schemes and of their quantum analogs. Given a simple algebraic group $G$, a parabolic subgroup $P_J$, and its unipotent radical $U_J$, we determine the ring structure of the cohomology ring $H^\bullet((U_J)_1,k)$. We also obtain new results on computing $H^\bullet((P_J)_1,L(\lambda))$ as an $L_J$-module where $L(\lambda)$ is a simple $G$-module with high weight $\lambda$ in the closure of the bottom $p$-alcove. Finally, we provide generalizations of all our results to the quantum situation.Comment: 18 pages. Some proofs streamlined over previous version. Additional details added to some proofs in Section

Role of healthcare workers in early epidemic spread of Ebola: policy implications of prophylactic compared to reactive vaccination policy in outbreak prevention and control.

Ebola causes severe illness in humans and has epidemic potential. How to deploy vaccines most effectively is a central policy question since different strategies have implications for ideal vaccine profile. More than one vaccine may be needed. A vaccine optimised for prophylactic vaccination in high-risk areas but when the virus is not actively circulating should be safe, well tolerated, and provide long-lasting protection; a two- or three-dose strategy would be realistic. Conversely, a reactive vaccine deployed in an outbreak context for ring-vaccination strategies should have rapid onset of protection with one dose, but longevity of protection is less important. In initial cases, before an outbreak is recognised, healthcare workers (HCWs) are at particular risk of acquiring and transmitting infection, thus potentially augmenting early epidemics. We hypothesise that many early outbreak cases could be averted, or epidemics aborted, by prophylactic vaccination of HCWs. This paper explores the potential impact of prophylactic versus reactive vaccination strategies of HCWs in preventing early epidemic transmissions. To do this, we use the limited data available from Ebola epidemics (current and historic) to reconstruct transmission trees and illustrate the theoretical impact of these vaccination strategies. Our data suggest a substantial potential benefit of prophylactic versus reactive vaccination of HCWs in preventing early transmissions. We estimate that prophylactic vaccination with a coverage >99% and theoretical 100% efficacy could avert nearly two-thirds of cases studied; 75% coverage would still confer clear benefit (40% cases averted), but reactive vaccination would be of less value in the early epidemic. A prophylactic vaccination campaign for front-line HCWs is not a trivial undertaking; whether to prioritise long-lasting vaccines and provide prophylaxis to HCWs is a live policy question. Prophylactic vaccination is likely to have a greater impact on the mitigation of future epidemics than reactive strategies and, in some cases, might prevent them. However, in a confirmed outbreak, reactive vaccination would be an essential humanitarian priority. The value of HCW Ebola vaccination is often only seen in terms of personal protection of the HCW workforce. A prophylactic vaccination strategy is likely to bring substantial additional benefit by preventing early transmission and might abort some epidemics. This has implications both for policy and for the optimum product profile for vaccines currently in development

Potential use of oxygen as a metabolic biosensor in combination with T2*-weighted MRI to define the ischemic penumbra

We describe a novel magnetic resonance imaging technique for detecting metabolism indirectly through changes in oxyhemoglobin:deoxyhemoglobin ratios and T2* signal change during ‘oxygen challenge’ (OC, 5 mins 100% O2). During OC, T2* increase reflects O2 binding to deoxyhemoglobin, which is formed when metabolizing tissues take up oxygen. Here OC has been applied to identify tissue metabolism within the ischemic brain. Permanent middle cerebral artery occlusion was induced in rats. In series 1 scanning (n=5), diffusion-weighted imaging (DWI) was performed, followed by echo-planar T2* acquired during OC and perfusion-weighted imaging (PWI, arterial spin labeling). Oxygen challenge induced a T2* signal increase of 1.8%, 3.7%, and 0.24% in the contralateral cortex, ipsilateral cortex within the PWI/DWI mismatch zone, and ischemic core, respectively. T2* and apparent diffusion coefficient (ADC) map coregistration revealed that the T2* signal increase extended into the ADC lesion (3.4%). In series 2 (n=5), FLASH T2* and ADC maps coregistered with histology revealed a T2* signal increase of 4.9% in the histologically defined border zone (55% normal neuronal morphology, located within the ADC lesion boundary) compared with a 0.7% increase in the cortical ischemic core (92% neuronal ischemic cell change, core ADC lesion). Oxygen challenge has potential clinical utility and, by distinguishing metabolically active and inactive tissues within hypoperfused regions, could provide a more precise assessment of penumbra

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

Temporal dynamics of aquatic communities and implications for pond conservation

Conservation through the protection of particular habitats is predicated on the assumption that the conservation value of those habitats is stable. We test this assumption for ponds by investigating temporal variation in macroinvertebrate and macrophyte communities over a 10-year period in northwest England. We surveyed 51 ponds in northern England in 1995/6 and again in 2006, identifying all macrophytes (167 species) and all macroinvertebrates (221 species, excluding Diptera) to species. The alpha-diversity, beta-diversity and conservation value of these ponds were compared between surveys. We find that invertebrate species richness increased from an average of 29. 5 species to 39. 8 species between surveys. Invertebrate gamma-diversity also increased between the two surveys from 181 species to 201 species. However, this increase in diversity was accompanied by a decrease in beta-diversity. Plant alpha-, beta and gamma-diversity remained approximately constant between the two periods. However, increased proportions of grass species and a complete loss of charophytes suggests that the communities are undergoing succession. Conservation value was not correlated between sampling periods in either plants or invertebrates. This was confirmed by comparing ponds that had been disturbed with those that had no history of disturbance to demonstrate that levels of correlation between surveys were approximately equal in each group of ponds. This study has three important conservation implications: (i) a pond with high diversity or high conservation value may not remain that way and so it is unwise to base pond conservation measures upon protecting currently-speciose habitats; (ii) maximising pond gamma-diversity requires a combination of late and early succession ponds, especially for invertebrates; and (iii) invertebrate and plant communities in ponds may require different management strategies if succession occurs at varying rates in the two groups

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article