Sleep disturbances, caused by jet lag, have probably been experienced by all transatlantic travelers. Jet lag reflects the limited phase-shifting capacity of the suprachiasmatic nucleus.125 Sudden 1-hour phase delays and advances, such as the ones caused by switching from summer time to winter time and vice versa, should not disrupt the circadian cycle, Inhibitors,research,lifescience,medical since these phase changes are well within the synchronization capacity of the clock. However, several days are required to adapt the circadian pacemaker to abrupt and large CDK activity daytime changes caused by transatlantic flights. Jet lag not only affects sleep-wake cycles, but also peripheral organs, such as the gastrointestinal

tract, liver, pancréas, and the kidney.126 As a consequence, heavy meals absorbed at “inadequate” daytimes after a transatlantic flight may cause indigestion. Moreover, during the jet lag period “poorly timed” urine production by the kidney may increase the frequency of urination during night hours. Adaptation is achieved faster after westbound journeys Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical than after eastbound journeys, presumably since the SCN has a greater capacity for phase delays than phase advances.125 This was documented in a rather objective manner by examining

the performance of top-class German athletes after transatlantic flights to Atlanta (westbound) or Osaka (eastbound). Jet lag-associated drops in performance disappeared after 5 days in Atlanta, but only after 7 days in Osaka.127 While occasional episodes of jet lag have probably no consequences on morbidity, chronic jet lag suffered by nurses and flight attendants on rotation shift work during extended time periods has been reported to significantly

increase breast cancer Inhibitors,research,lifescience,medical risk.128 Moreover, mice subjected to light-dark regimens causing chronic jet lag show Inhibitors,research,lifescience,medical a sharp increase in morbidity and mortality.129 If animals kept under such conditions receive tumor grafts, the tumors proliferate more rapidly than in control mice.130 The molecular mechanisms linking circadian rhythms to tumor biology remain to be elucidated, but several observations hint towards the implication because of Per genes. Thus, a large fraction of mPerl mutant mice die of cancer, most frequently of spontaneous lymphomas.131, 132 Perhaps relevant to the increased breast cancer incidence in women with chronically disrupted circadian rhythms, Chen and coworkers reported that 56 out of 59 tumor samples from Taiwanese woman displayed strongly deregulated PER1, PER2, and PER3 gene expression.133 In these tumors, epigenetic silencing through DNA methylation, rather than mutations was responsible for the reduced levels of PER proteins. Perturbation of circadian clock function can also cause psychiatric ailments, SAD (seasonal affective disorder) being probably the most common among them.

65,68,69 Given their differential nature of see more expression and because of the local regulation of mRNA translation, the role of miRNAs in numerous biological phenomena, including neuronal development, cell proliferation, cell cycle, neurogenesis, synaptic development, axon guidance, and neuronal plasticity, have been studied.70-73 miRNAs: potential regulators of neurogenesis and neural plasticity Inhibitors,research,lifescience,medical miRNAs in neurogenesis Adult neurogenesis, the process of generating

new neurons from neural stem cells, plays a critical role in synaptic plasticity, learning and memory, and mood regulation.74,75 In the mammalian brain, neurogenesis occurs throughout adulthood in the hippocampus (subgranular zone [SGZ] of the dentate gyrus) and olfactory bulb (subventricular zone [SVZ]). Neurogenesis in the SVZ is important for olfactory learning,76 whereas hippocampal neurogenesis is involved in memory and spatial learning.77 Numerous studies suggest that stress and MDD are associated with decreased hippocampal neurogenesis.78-80 Additionally, disturbed adult neurogenesis, possibly resulting Inhibitors,research,lifescience,medical in a malfunctioning of hippocampus, may contribute to cognitive deficits.81 Conversely, hippocampal neurogenesis buffers stress responses and depressive behavior.82

Enriched environment, exercise, electroconvulsive therapy, deep brain stimulation, and antidepressants Inhibitors,research,lifescience,medical increase hippocampal neurogenesis.83 The regulatory factors that control adult neurogenesis are currently under investigation; however, recent studies demonstrate Inhibitors,research,lifescience,medical that miRNAs play a role in both embryonic as well as adult neurogenesis.84 For example, Choi et al56 demonstrated

that olfactory tissues express more than 100 distinct miRNAs, the most abundant being the miR-124a and let-7 variants and the family of miR-200. To determine whether miRNAs are required during olfactory neuronal development, these investigators analyzed embryonic tissues in which Dicer function was specifically ablated in olfactory progenitor cells. They showed that the loss of miRNA function from olfactory progenitor cells produced Inhibitors,research,lifescience,medical no alterations in patterning. In contrast, they noted that terminal differentiation of the olfactory progenitor pool into mature olfactory neurons does not occur and that to the olfactory precursor cell population is not maintained. Dicer depletion also impacts proliferation and cell death, migration, and differentiation during corticogenesis as assessed by McLoughlin et al85 in the developing brain. Using markers for proliferation and in vivo labeling, they showed reduced numbers of proliferating cells, altered cell cycle kinetics from embryonic day 15.5 (E15.5), distributed progenitor cells throughout the cortex (rather than restricted to the SVZ and ventricular zones), and increased cortical cell death as early as E15.5. DGCR8 heterozygous mice also show reduced cell proliferation and neurogenesis in adult hippocampus.

Our patient had none of the classic predisposing factors for hepatic lymphocytic proliferation, such as chronic viral hepatitis, HIV, EBV or autoimmune hepatic disease. However, other mechanisms for the development of NHL in celiac disease may be implicated. It is also possible that this may be an entirely fortuitous association. Acknowledgements Disclosure: The authors declare

no conflict of interest.
In the United States, colorectal cancer (CRC) is the third most common incident cancer and the third highest cause of cancer death for both men and women (1). When CRC is diagnosed at an early stage, the 5-year relative survival is 90.4%, but for patients with metastatic disease, 5-year survival Inhibitors,research,lifescience,medical is only 11.6% (2). Factors associated with stage at presentation and survival include race (3), gender (3), socioeconomic status (SES) (4,5), and molecular abnormalities, such as abnormal expression of p53 (6). Although SES has emerged as an important factor relating to CRC, the mechanism through which it affects survival Inhibitors,research,lifescience,medical has not been ABT-869 datasheet elucidated. There is a need to identify genetic factors that contribute to SES differences and to progression of CRCs. Genetic alterations, including those in the p53 gene, occur during the development of CRCs (7). Patients whose CRCs exhibit nuclear accumulation of p53 (p53nac) have decreased survival

Inhibitors,research,lifescience,medical after resection, and p53nac may be a useful Inhibitors,research,lifescience,medical prognostic factor (8,9). Although patient race/ethnicity and SES are related, they do not measure the same construct

(10). Therefore, it is important to determine if SES and race are associated with p53nac. Environmental factors associated with SES may be related to the genetic alterations in carcinogenesis. For women with breast cancer, p53 mutations were associated with SES Inhibitors,research,lifescience,medical and may have an association with the poorer prognosis of women of low SES (11). Thus, there is a need to identify the genetic factors that contribute to SES differences and progression of CRCs. This study aimed to evaluate the association between measures of SES, including health insurance and employment status, and p53nac among a cohort of patients with CRC. Patients and methods Patients An existing database for a cohort of patients (N=1,135) who received curative or palliative resection for sporadic CRC at the University of Alabama at Birmingham from 1981 to 2002 was utilized for this study. This investigation, which no was approved by the Institutional Review Board at the University of Alabama at Birmingham, did not require informed consent. The data were obtained from medical records, physician charts, and surgical pathology and radiology reports. For a subset of patients, archival tissues were obtained and evaluated for p53nac status (N=590). Only patients with data on both SES and p53nac status were included for this analysis (N=249).

24 Although the results of this control study provide some positive information, we felt that it was far too limited in its design: a single antidepressant was administered IP (instead of orally as in clinical psychiatry) to unstressed control rats, ie, very different conditions from those required to assess the potential psychoneuroendocrine benefit of the psychotropic agent. This is why we performed a second series of experiments with imipramine and desipramine that took into account the limits of the first paradigm.25 Repeated fluoxetine treatment in SHR and WKY receiving imipramine and desipramine In the imipramine and desipramine experiments, it was observed that following a 24-h wash-out period, WKY displayed

higher Inhibitors,research,lifescience,medical plasma antidepressant and antidepressant metabolite levels than SHR. Fluoxetine pretreatment decreased [3H]citalopram binding at midbrain 5-HTTs, whereas tricyclic antidepressants and fluoxetine decreased [3H]ketanserin binding at cortical 5-HT2A receptors, [3H]CGP-12177 binding at cortical β-adrenoceptors, Inhibitors,research,lifescience,medical and [3H]nisoxetine binding at midbrain noradrenaline (NA) transporters in both strains. None of the antidepressants affected [3H]8-OH-DPAT binding at hippocampal 5-HT1A receptors. It was notable that repeated restraint triggered a desipramine-sensitive 140 % increase in hypothalamus [3H [nisoxetine binding in WKY, but not in SHR; moreover, plasma adrenocorticotropin-releasing

hormone Inhibitors,research,lifescience,medical DAPT secretase solubility dmso responses to a 5-min open field test were amplified by prior repeated restraint in both strains, but desipramine Inhibitors,research,lifescience,medical prevented such an amplification in WKY only. However, the elevated

plus-maze and open field behaviors of SHR and WKY were unaffected by desipramine pretreatment. A simple conclusion of these experiments is that they clearly show that the SHR and WKY strains may be useful in understanding how genetic differences in noradrenergic responses to stress and desipramine treatment Inhibitors,research,lifescience,medical impact on adaptive processes. Genetic variability in the rat 5-HTT The experiments described above all focused on one main question: do individuals that differ in their behavioral responses to novel environments also differ with respect to key central monoaminergic responses to stressors and/or antidepressants? The results underline how comparisons between rat strains may allow the detection of models of some value for understanding the basis of the interindividual variability in fear responses, whether these are linked to behavior (eg, the socially below stressed LEW) or neurochemistry (eg, the restrained WKY). The quest for the mechanisms explaining such strain-dependent characteristics undoubtedly require intense effort, at least effort that is beyond the scientific and human capacities of our research group. Accordingly, we recently decided to change our scientific goals by trying to focus on the genetics of central serotonergic systems, leaving behavioral and neuroendocrine research topics aside, at least in the preliminary stages of research.

20 Dementia with Lewy bodies (DLB) completely breaks the traditional mold in dementia by having attention deficits identified as a core feature of the syndrome.22 These patients also have larger attentional deficits than AD patients while, like HD and VaD patients, they have relatively preserved episodic memory.21,23

Further, the attentional deficits seen in DLB are not. only quantitatively, but Inhibitors,research,lifescience,medical also qualitatively different from those seen in AD. For example, the variability in reaction times in a 90-s computerized test of attention, choice reaction time, can discriminate between the two types of dementia with a sensitivity of 81% and a specificity of 92%.21 Importantly, different profiles of attentional impairment, can be seen in all the major types of dementia (VaD, AD, and DLB21), probably reflecting the differing etiologies of the conditions. Thus, DLB can also be differentiated from VaD Inhibitors,research,lifescience,medical with a sensitivity of 81% and a specificity of 82%, while AD can be differentiated from VaD with a sensitivity of 64% and a specificity of 77 %.21 Attentional impairments have also been seen in first time diagnosed unmeditated Parkinson’s disease patients,24 Parkinson’s dementia,25 and elderly Inhibitors,research,lifescience,medical stroke patients actually free from dementia.26 Besides marked deficits to

attention,27 demented patients show marked reductions in the speed with which they can recognize previously presented information (words, pictures, faces5,6,23). These deficits are also characteristic of mild cognitive impairment. (MCI)28 and add a further dimension to our knowledge of the cognitive deficit profiles in the dementias that have gone undetected by nonautomated assessments like the ADAS. The behavioral impact of delays in time to retrieve information from working Inhibitors,research,lifescience,medical and secondary memory is manifest in a variety of behavioral situations. For example, in social situations, in which not only is the patient clearly forgetful,

but even when items are retrieved or objects (or people) recognized, the increased time lag makes social Inhibitors,research,lifescience,medical interactions more stressed and unsatisfactory. Other examples are patients not remembering the name of someone until after they have passed by in the street, or remembering to do something too late or in those the wrong context. Historical perspectives on cognitive assessment of dementia Alzheimer’s disease Since the registration of the anticholinesterase, tacrine, for the symptomatic treatment of AD in the late 1980s, the cognitive outcome measure most frequently used in clinical drug trials for new dementia drugs has been the cognitive subscale of the ADAS (ADAS-COG). However, the ADAS-COG Paclitaxel ic50 features some well-recognized deficiencies,29-31 which, as the following examples will illustrate, have been recognized by the International Working Group on Dementia Drug Guidelines7: A generally acknowledged limitation of the ADAS-COG is that it lacks a subset for attention. […

Heart malformations, cleft lip and palate, skeletal deformities, diaphragmatic hernias, malformations of the central nervous system, gastrointestinal atresias, and urogenital malformations have most commonly been reported.100 Heart, failure and craniofacial clefts are the

malformations with the highest incidence in children of women with epilepsy.100 In order to estimate the increased Inhibitors,research,lifescience,medical risk of malformations accordingly, one has to keep in mind the spontaneous malformation rates in the general population. Figures in the literature vary from 0.4% to 6.4%. 113 Holmes et al108 reported an incidence of 1.8%, according to other reports it ranges between 2% and 3%.71,114 Malformations in children of women with epilepsy who did not take AEDs Inhibitors,research,lifescience,medical during pregnancy are similar and range between 0% and 3.5% (in smaller

cohorts than in the studies on the general population).108,109,115,116 This suggests no epilepsy-specific additional risk. However, this is not necessarily true, since the underlying epilepsy syndromes in the above patients were apparently less active, since chronic medication was not Inhibitors,research,lifescience,medical required. Therefore data on active epilepsies without AED intake that would answer the question of epilepsy-specific teratogenicity do not exist, at least not in countries where sufficient epidemiological studies on the topic have been performed. Whether or not children of fathers with epilepsy who are on AEDs have an increased teratogenic risk is a matter of controversy.106,117 Hie available data do not allow to claim such an elevated risk unequivocally. Inhibitors,research,lifescience,medical An independent impact of AEDs is Pomalidomide supplier probable, since the risk of malformations is also higher in children of mothers who were on AEDS for reasons other than epilepsy.108 Risk in women with epilepsy taking AEDs In women with epilepsy on AED therapy the teratogenic risk for major congenital malformations was reported Inhibitors,research,lifescience,medical to range between

4% and approximately 14%.69,108,109,118,119 The ongoing pregnancy registries report incidence rates of 3.7% in Taiwan,120 4.2% in the UK registry,103 and 6.4% in Germany.96 Since association between the risk of malformations and the amount of individual serum peak concentrations has been suggested, multiple dosing, especially in the case of VPA, should be considered.121 Mephenoxalone Minor congenital malformations such as minor craniofacial abnormalities, epicanthus, or hypertelorism are relatively common in children of women with epilepsy and treatment with AEDs. However, it is almost, impossible to assess precisely the impact, of AEDs. It is apparent that these abnormalities are not drug-specific as was previously assumed, and that they are observed under the influence of each of the classical AEDs.71,122,123,124 Reliable data on new AEDs are not. yet available. A realistic estimate suggests that minor abnormalities are twice as frequent as in the general population (28% versus 14%).125 Combinations of AEDs Polytherapy is a risk factor for congenital malformations, including new AEDs.

The less common

types include ACTHoma, CRHoma, Serotoninoma, Calcitoninoma, GHRHoma, GRFoma, and parathyroid hormone-related peptide tumor. Nonfunctioning PETs are either an incidental finding or are associated with an expanding mass rather than a hormonal syndrome. Quizartinib nonfunctional tumors tend to present at later clinical stages with symptoms attributable to mass effect or metastases. Although nonfunctional tumors do not produce specific clinical syndromes, they Inhibitors,research,lifescience,medical may secrete inactive amine and peptide products such as neurotensin, alpha-subunit of human chorionic gonadotropin (alpha-hCG), neuron-specific enolase, pancreatic polypeptide (PP) and chromogranin A. Histopathology findings PETs may be either well circumscribed or infiltrative. The cut surface appears red to tan, reflecting the abundant microvasculature, or sometimes yellow because of high lipid content. Morphologically, well-differentiated PETs have characteristic “organoid” arrangements Inhibitors,research,lifescience,medical of the tumor cells, with solid, nested, trabecular, or ribbon-like/gyriform, tubuloacinar/psuedoglandular and mixed patterns. The cells are relatively uniform, with round to oval nuclei, Inhibitors,research,lifescience,medical coarsely granular and stippled (imparting the classical “salt-and-pepper” appearance) chromatin, and variable from pale to moderately eosinophilic cytoplasm. The cells produce abundant neurosecretory granules, as

reflected in the strong and diffuse immunohistochemical expression of neuroendocrine markers Inhibitors,research,lifescience,medical such as synaptophysin and chromogranin. Electron microscopy can identify secretory granules. There is usually minimal pleomorphism but less commonly there can be anaplasia, mitotic activity, and necrosis (1). Generally, the histologic features of the tumor do not correlate with anatomic location or hormone production, but there are exceptions:

amyloid deposition (insulin-associated peptide) Inhibitors,research,lifescience,medical often indicates an insulin-secreting PET, and glandular architecture with abundant psammoma body formation is usually seen in periampullary somatostatin-secreting PETs (1). The morphologic spectrum of these tumors can be variable, and the pathologic differential diagnosis includes chronic pancreatitis with neuroendocrine hyperplasia, poorly differentiated ductal adenocarcinoma, solid pseudopapillary tumor, acinar cell carcinoma, and pancreatoblastoma (6). However, serologic or immunohistochemical Tolmetin evidence for elevated hormones may be identified for PETs. PETs show tissue immunoreactivity for markers of neuroendocrine differentiation (chromogranins, synaptophysin, neuron-specific enolase, PGP9.5 and CD56) and may secrete various peptides and hormones. Expression of peptides such as insulin, glucagon, PP, somatastain, gastrin or VIP is common, and most functional PETs can be shown to produce the appropriate peptide by immunohistochemistry. In addition, minor cell populations producing a variety of other peptides are commonly detectable.

In this model, significant neuropathological damage is largely absent. In comparison with studies on human and experimental TLE, work on models of epilepsies with neocortical seizure foci has been relatively scarce, even though such models can also be validated in human in vitro studies. Models of TLE have proven useful as a complementary strategy to investigations on human epileptic brain tissue. In experiments on human tissue, a fundamental problem is the lack of living control tissue. Very rarely, nonepileptic human control tissue is available from

the penumbra of tumor resections in the temporal lobe. Other than this rare commodity, experimenters are left #BIIB057 cost keyword# with the option of comparing epileptic tissue with autopsy control tissue, which is impossible for physiological and some molecular biological approaches. A further, commonly used approach is to compare tissue from patients with AHS vs lesion-associated epilepsy. This strategy has allowed the investigation of the expression of candidate molecules associated Inhibitors,research,lifescience,medical with changes present only in one of these patient Inhibitors,research,lifescience,medical groups. For instance, molecules important

in synaptic reorganization would be expected to be present in specific areas in AHS, but not in lesion-associated epilepsy. Studies in animal models, on the other hand, always require validation with studies on human tissue to demonstrate their relevance to the human disorder unequivocally11 However, animal models Inhibitors,research,lifescience,medical do complement human studies in important ways. Firstly, animal models allow molecular and functional changes to be studied in detail without the constraints imposed by the lack of control material in experiments with human tissue. Further, having identified clear molecular changes, animal models allow us to determine the importance of such changes for hyperexcitability and

epileptogenesis. This question is important because a large number of regulated candidate molecules have been identified, all of which may be potentially important isothipendyl Inhibitors,research,lifescience,medical in the development of epilepsy. A major challenge will be to determine which of these manifold changes are functionally important in common forms of epilepsy. To decipher the causal role of candidate genes, it has become increasingly accepted that it is necessary to generate cell-specific and inducible gain – as well as loss-of-function models on a more systematic scale than previously attempted. Such approaches may be realized using viral transfer of small interfering RNAs (siRNAs), or transgenic models that allow cell-specific and inducible genetic modifications. Finally, animal models allow to study some aspects of epileptogenesis, which is virtually impossible in human tissue, because specimens are only obtained late during the disease course.

Case Report A 55-year-old obese male presented with an intermittent right scrotal mass of 6 years’ duration. The mass lesion protruded through the right inguinal canal before Docetaxel voiding and reduced in size thereafter. The patient complained of a reduction

in the force, caliber, intermittency, and frequency of urination. Scrotal examination revealed a soft scrotal mass with size variation related to voiding. Inhibitors,research,lifescience,medical A digital rectal examination revealed only mild prostatic enlargement. There was no underline disease in the patient’s past medical history, and his surgical history was negative. Urinalysis and renal function test and serum chemistry parameters were normal. Scrotal sonography, Inhibitors,research,lifescience,medical conducted to characterize the nature of the mass, demonstrated a hypoechoic lesion in the scrotum which stretched proximally to the intra-abdominal portion of the bladder. Change in the volume of the lesion during micturition was a diagnostic clue. Excretory urography was performed and showed a duplicated system in the left kidney with deviation of the left orifice to the right side of the trigon (figure 1), and cystography

illustrated herniation of the Inhibitors,research,lifescience,medical bladder to the right scrotum (figure 2). Figure 1 An intravenous urogram, showing a duplicated system in the left kidney and the fusion of both ureters in the distal portion with deviation of the left orifice to Inhibitors,research,lifescience,medical the right side of the trigon. Figure 2 Cystogram, demonstrating herniation of the bladder to the right scrotum. The patient was scheduled for the surgical repair of the hernia under spinal anesthesia

and in supine position. After placement of a urethral catheter, right inguinal incision was made. Next, the herniated bladder was dissected and reduced to the pelvic cavity. The floor of the right Inhibitors,research,lifescience,medical inguinal canal was thereafter reinforced with Prolene mesh. Finally, the urethral catheter was removed the day after surgery, and the patient was discharged after successful voiding. Follow-up cystography was done one month later and revealed no herniation (figure 3). The patient’s urinary complaints were significantly Resveratrol reduced after surgery. Figure 3 Follow-up cystography after surgery, revealing no herniation. Discussion Bladder hernia is usually asymptomatic, often occurs on the right side, and is direct in type. Small bladder hernia is usually asymptomatic, whereas large bladder hernia presents with intermittent swelling in the groin or the scrotum and lower urinary tract symptoms such as frequency, nocturia, and urgency, which may secondary to bladder outlet obstruction or secondary infection that is often superimposed.2 Large scrotal bladder hernia presents with two-stage micturition involving natural bladder emptying with a second-stage voiding by manual compression of the hernia.5 Change in the size of the hernia is correlated with the degree of bladder filling.

In the USA, the expansion of the early activation/auto launch strategy has shown some success when ground/air EMS services were dispatched simultaneously for attending to either critical injury or for persons further than 10 miles away from the hospital [11,12]. In BC, test data from the British Columbia Ambulance Service (BCAS) indicates that HEMS based on 911 interrogations is an effective basis for auto launch. The BCAS is seeking to extend the Vancouver-based early response/auto launch protocol to either Kelowna General Hospital (KGH) in Kelowna or the Royal Inland hospital (RIH) in Kamloops within the Inhibitors,research,lifescience,medical Interior Health Authority (IHA) in an effort to reduce the

time from insult of traumatic injuries to the arrival at tertiary care. The IHA provides services to the largest population in the province outside greater Vancouver and greater Inhibitors,research,lifescience,medical Victoria municipal

areas, servicing over 650,000 people distributed in highly pocketed areas throughout its region. Both KGH and RIH trauma centres provide 24-hour emergency services and core specialties including general surgery, orthopedics, ICU and neurosurgery. BCAS required the development of a defensible quantitative model that could identify where an additional helicopter resource could be placed that would shorten the transport time for major trauma patients Inhibitors,research,lifescience,medical to tertiary care and also be in a position to capture the greatest number of potential trauma Inhibitors,research,lifescience,medical incidents

as possible. We proposed a location optimization methodology derived from a geographic information system (GIS) to support this decision-making process. Our method is based on spatial analysis Inhibitors,research,lifescience,medical of multiple data sources, combined with a critical review of potential locations for the expansion of the auto launch program-based on analytical results. The model derives population catchments for each tertiary facility by amalgamating population data, road network travel times and impedances as outlined in previous health service optimization studies [13,14]. The integration of these datasets PKA inhibitor research buy results in secondly a highly dynamic and spatialized database of current accessibility and demand on acute surgical care facilities within the IHA and delivers a quantitative assessment of where best to extend the early response/auto launch program. Methods Defining the question Pre-hospital services in British Columbia BC are provided by the BCAS which is the largest single provider of emergency health care in Canada; BC is currently the only province that operates its own ambulance service. Province wide, BCAS operates out of nearly 190 stations with the goal of providing access and timely delivery of pre-hospital emergency care; they respond to over 500,000 emergency calls per year [15].