They were kept under standard conditions (light/dark cycle: 12 h;

They were kept under standard conditions (light/dark cycle: 12 h; humidity: 25-35%; and temperature: 22-28˚C) with standard food and water ad libitum. All the animal procedures were approved by the Institutional Committee for Care and Use of Animals. Materials Streptozotocin was obtained from Teva Parenteral Medicine

Inc. (Irvine, CA, USA). Nicotinamide (NA) was purchased from Sigma-Aldrich Chemical Co. (Steinheim, Germany). Inhibitors,research,lifescience,medical Streptozotocin and NA were dissolved in sodium chloride (0.9%). Ketamine and Xylazine were obtained from Alfasan (Woerden, Holland). Triphenyltetrazolium Chloride (TTC) was obtained from Sigma-Aldrich Chemical Co. (Steinheim, Germany). Kits for the measurement of coronary artery effluent creatine kinase (CK-MB) were obtained from Pars Azmoon Company (Pars Azmoon, Tehran, Iran). Experimental Design The animals (n=35) were randomly allocated to five groups, including a type 2 diabetes control group (n=7), a type 2 diabetes group (n=7), a renovascular Inhibitors,research,lifescience,medical hypertensive (HTN) group (n=7), a sham-operated group (Sham) (n=7) as a control for the renovascular hypertensive group, and a simultaneous type 2 diabetes (n=7) and renovascular hypertensive (HTN) group Inhibitors,research,lifescience,medical (n=7). Experimental Protocol Induction of Diabetes and Renovascular Hypertension Type 2 diabetes was induced by injecting the animals with single intraperitoneal administrations of NA (110 mg/kg) 15 min before single intraperitoneal administrations

of STZ (60 mg/kg).11 Seven days later, the animals’ blood glucose was determined using a Glucometer (Accu-Chek® Inhibitors,research,lifescience,medical active, Mannheim, Germany), and those with fasting blood glucose (FBG) levels higher than 126 mg/dl were taken as having type 2 diabetes.12

Six weeks after the injection of NA and STZ or normal saline, the animals were Talazoparib subjected to sham operation Inhibitors,research,lifescience,medical or placement of solid Plexiglas clips on the left renal arteries to induce two-kidney, one-clip renovascular hypertension as was described previously.13 Briefly, under Ketamine (60 mg/kg) and Xylazine (8 mg/kg) anaesthesia, incisions were made in the left flanks, and the left renal arteries and veins were exposed. The arteries were gently dissected from the veins, and solid Plexiglas clips (internal diameter=0.20-0.22 Non-specific serine/threonine protein kinase mm) were placed on the left renal arteries. The abdominal wall and skin incisions were then sutured using absorbable (catgut-3/0) and non-absorbable (silk-3/0) suture materials, respectively. The sham-operated animals were subjected to the same procedure, but no clip was placed on the left renal arteries.13 Four weeks after the sham-operation or induction of renovascular hypertension, the animals’ systolic blood pressure (SBP) and heart rate (HR) were measured using the noninvasive tail-cuff (Chart 5.0 software, PowerLab 4/30, ADInstruments Inc., MA, Sydney, Australia) method. Three consecutive measurements of blood pressure, which had a difference of less than 5 mm Hg, were considered valid.


epidemiology of rotavirus varies by setting [6] Seas


epidemiology of Libraries rotavirus varies by setting [6]. Seasonality of infection is prominent in temperate climates while a low prevalence is maintained throughout the year in tropical countries [7]. The mode of transmission, though believed to be mainly feco-oral, is also possibly airborne and person-to-person because infection occurs in childhood irrespective of sanitary conditions [8]. Rotaviral gastroenteritis is usually accompanied by vomiting see more and fever and results in severe disease among infants [9]. Rotavirus is excreted in large numbers during diarrhea and the virus can remain infectious on inanimate surfaces, moist surfaces and hands. This report describes rotavirus infection detected by stool Epacadostat research buy testing in children followed from birth to three years of age, with sampling during and in the absence of diarrhea. This study was conducted from 2002 through 2006 in three contiguous slums in Vellore, India after approval by the institutional review board of the Christian Medical College, Vellore. The study conduct, recruitment, and sample collection methods have been published previously [10]. Briefly, a birth cohort of 452 children was followed from birth till three years of

age, analysis was restricted to the 373 children who completed three years of follow-up. Surveillance of children for rotavirus infection was done by screening bimonthly stool samples and diarrheal stool samples, and clinical data were collected to record diarrheal severity below using the Vesikari score

with scores <5 considered mild, 6–10 moderate, 11–15 severe and 16–20 very severe [11]. In case of a surveillance sample, positive samples detected by ELISA (Dako Rota IDEIA, Ely, UK) were genotyped by reverse-transcription polymerase chain reaction (RT-PCR) for VP7 and VP4 amplification while for a diarrheal sample, irrespective of the ELISA result, one sample per episode was screened using RT-PCR for VP6 before genotyping [12]. The definitions for symptomatic and asymptomatic rotavirus infections used in this study are given in Table 1. Age-specific incidence and seasonality of symptomatic and asymptomatic infections were studied. The incidence rates were obtained by Poisson regression equations and frailty models adjusted for clustering of disease/infection within a child. For cumulative incidence of rotavirus infection, Kaplan–Meier estimates of median time to infection were calculated and compared between children infected with rotavirus overall and with specific genotypes. Factors influencing rotavirus infection as well as disease rates were studied using Poisson regression. To study the risk factors for rotavirus infection, children who experienced rotavirus infection in the first year were compared to children who did not experience rotavirus infection in the first year using multiple unconditional logistic regression.

It is beyond our scope even to attempt a summary of this expandin

It is beyond our scope even to attempt a summary of this expanding literature. Instead, we will present some of the main dimensions of memory that this work has highlighted as having potential for understanding neural mechanisms. Procedural memory Both clinical and functional neuroimaging studies have supported distinct neural systems involved in “procedural” learning and memory, which differ from those regulating “declarative” memory. Procedural memory refers to retention of skills acquired by repeated

Inhibitors,research,lifescience,medical practice, while declarative memory refers to knowledge of content of previously experienced situations. As established by the case of HM and confirmed in functional neuroimaging studies, declarative memory involves the hippocampus and associated temporal and frontal cortices. Procedural memory is different, as has been Inhibitors,research,lifescience,medical established by psychologists long ago, in multiple respects. It is mostly unconscious and its learning depends more on rote repetition than on insight. Furthermore, once learned, it is retained after the passage of years. Examples are riding a bicycle, skiing, driving a car, and swimming. If trained in these skills at an early age, one can retain these skills Inhibitors,research,lifescience,medical and, while rusty after prolonged lack of practice, would show evidence of prior learning by rapid return to earlier skill levels. This learning takes place in regions outside the hippocampus, predominantly in cerebellum,

basal ganglia, and sensorimotor cortex. Declarative memory Declarative memory refers to specific autobiographical events that can be recounted by an individual. For example, a memory of your birthday when

you received a PI3K inhibitor bicycle as a gift. One is able to place the event in time and context. Further distinctions have been made within declarative memory, between episodic Inhibitors,research,lifescience,medical and semantic Inhibitors,research,lifescience,medical memory. Semantic memory is factual, whereas episodic memory contains representations of past experience that include sensory, perceptual, conceptual, and affective features.11 Episodic memory can fade rapidly and is subject to distortions.12 All forms of declarative memory appear to recruit medial temporal structures. However, there is evidence that prefrontal regions are involved in the encoding of new episodic memories. More recently an important distinction within episodic memory has been proposed—between recollection and familiarity.13 Recollection reflects the retrieval of information, whereas familiarity reflects the passing of a threshold where one recognizes a stimulus Cell press or event as having been experienced. There is much current research attempting to identify distinct neural systems related to recollection and familiarity.14 Note that another domain, working memory, is often discussed in functional neuroimaging studies. Although that construct described by Baddeley15 encompasses mnemonic processes as it relates to events immediately preceding the present, its emphasis is on the rapid replacement of information by new input entering our mental scratch pad.

2 The issue of terminology concerns everyone: researchers, clini

2 The issue of terminology concerns everyone: researchers, clinicians, SKI-606 mouse public policy decision makers, bioinformaticists, and laypeople, as well as other stakeholders. The US National Human Genome Research Institute, and US National Cancer Institute have created useful glossaries: Talking Glossary of Genetic Terms, US National Human Genome Research Institute [] Dictionary of Cancer Terms, US National Cancer Institute [] There is an excellent glossary in the new, comprehensive, two-volume book set, Genomic and Personalized Medicine,

which was published by Elsevier/Academic Press in 2009 .3 Inhibitors,research,lifescience,medical This book set, available in print or electronically Inhibitors,research,lifescience,medical through ScienceDirect, is an excellent starting place for people who are trying to get an understanding of the many concepts and issues that comprise personalized medicine. The former US HHS Secretary, Michael O. Leavitt, wrote the foreword to this book. Section 12 of this book, titled “Neuropsychiatrie Disease Inhibitors,research,lifescience,medical Genomic Medicine,” includes eight chapters that discuss dementia, Parkinson’s disease, epilepsy, ophthalmology, neuromuscular

disorders, psychiatric disorders, depression, and bipolar disorder. Genomic and Personalized Medicine [] In short, the terminology that is used Inhibitors,research,lifescience,medical in article databases such as PubMed as well as on various Web sites is wideranging and makes it difficult to pull all of the relevant information on this topic together. Additional Web resources There are thousands of Web sites that pertain to personalized medicine and its subtopics. Any collection, especially one in a “brief report” such as this,

is necessarily a “selected” list. The following Inhibitors,research,lifescience,medical Web sites are provided as a sample of the range of projects and Web sites that are available: US National Institutes of Health (NIH) National Human Genome Research Institute (NHGRI) [] PhenX Toolkit, NI IGRI [] ENCODE Project: ENCyclopedia of DNA Elements, NHGRI [] Ethical, Legal, and Social Implications ELSI Research Program, NHGRI [] until Human Genome Project, NHGRI [] Pharmacogenetics Research Network, National Institute of General Medical Sciences (NIGMS) [] Environmental Genome Project, National Institute of Environmental Health Sciences (NIEHS) [ programs/egp/] NIH Chemical Genomics Center [] NIH Data Sharing Policy for Genome Wide Association Studies (GWAS) [] NIH Roadmap for Medical Research [http://nihroadmap.nih.

4, maintaining the ratio SBF volume (mL) per adsorbed ibuprofen

4, maintaining the ratio SBF volume (mL) per adsorbed ibuprofen mass (mg) equal to 1. Continuous magnetic stirring was maintained during the delivery experiments, to avoid limitation of the delivery rate by external Selleck Bioactive Compound Library diffusion constrains. The loaded ibuprofen concentration was monitored by UV-vis spectroscopy at a wavelength of 272nm and the delivered ibuprofen at 222nm. All samples were measured by triplicate and average values were used for the graphical

presentation and data treatment. The standard deviations are less than 5% in all cases. Characterization of meso- and microporous materials was carried out by X-ray diffraction (XRD), in a Siemens 5005 X-ray diffractometer, using Cu-Kα (Ni filter) operating at 40keV and 20mA. Inhibitors,research,lifescience,medical Fourier Transformed Infrared spectroscopy (FTIR) was performed Inhibitors,research,lifescience,medical in a Nicolet 560 equipment, scanning electron microscopy (SEM) analysis in a Hitachi FE S-4500 operating at 8 and 10keV, transmission electron microscopy (TEM) in a Phillips CM-10 operating at 80keV, and a Tecnai G20 FEI, superficial area measurements by N2 adsorption were taken in a Micromeritics Inhibitors,research,lifescience,medical ASAP 2010, previously degassing of the

samples was performed at 320°C, for 4h for the unloaded samples, and at 100°C, for 24h for the drug-loaded samples. Thermogravimetric analyses were carried out in an SDT Q600 TA Instruments equipment, using a heating rate of 10°C/min, from 30 to 900°C, in air atmosphere. The UV experiments were carried out in a Perkin Elmer Lamda2 UV spectrometer. 3. Results and Discussion Ibuprofen is used as analgesic and anti-inflammatory and in general acts as a vasoconstrictor; its molecular size is 1.3 × 0.6nm (Figure

Inhibitors,research,lifescience,medical 1). It is used as a model molecule in experiments of controlled drug release, due to its stability, its applicability, and its well-known behavior. Due to its dynamical diameter sizes, this molecule is interesting to compare the drug adsorption and release capability of solids of very different pore size, such as zeolites (with a pore size of 0.7nm) and mesoporous materials with pore size of 50nm. This can give information of the accessibility Inhibitors,research,lifescience,medical of this molecule to the pore channels and therefore evaluate the potential of this solids to be used as drug carriers. Figure 1 Ibuprofen molecule. Therefore, mesoporous SBA-15 see more materials, with different pore size and beta zeolite, were used as nanocapsules. They are both silica based materials with silanol groups in their internal and external surfaces, that can interact with the carboxylic acid groups of IBU via hydrogen bonding or with the pi electron density of the aromatic ring. The pore architecture of the mesoporous materials was modified by control of the pH of the synthesis gel, working in conditions above and below the isoelectric silica point. Figure 2 shows the dramatic change of particle morphology by SEM, for the materials synthesized at pH 0 and 4.5, identified as SBApH0 and SBApH4.5.

Unfortunately, the available data that address this hypothesis ar

Unfortunately, the available data that address this hypothesis are sparse due to the challenge of studying an adequate number of social groups. Depressive behavior may be only one in a range of potential responses to social subordination stress. Studying the attributes of subordinates that do not become depressed may provide valuable insights about alternative stress responses. Single caging may be considered a stressor as ABT888 it increases heart rate in adult female cynomolgus monkeys (Watson et al., Apr 1998). We measured circulating biomarkers and heart rate (HR) in single caged monkeys immediately prior to social housing. Females that had higher overnight HRs in single cages were later more likely to exhibit behavioral

depression in social groups, suggesting that stress sensitivity may increase the likelihood of a depressive Modulators response to social stress (Shively et al., Sep–Oct 2002). Likewise the monkeys that later developed behavioral depression in social groups had decreased cortisol secretion in a corticotropin-releasing hormone (CRH) challenge test, decreased circulating insulin-like growth factor-1 (IGF-1) concentrations, lower activity levels,

ABT-199 cell line and higher total plasma cholesterol (TPC) concentrations and ratios of TPC:high-density lipoprotein cholesterol (HDL-C) concentrations while singly caged. These data suggest that individuals at increased risk for a depressive response to social stress also differ in a number of

physiological systems associated with increased disease risk (Shively et al., Apr 2005). In a study of 46 ovariectomized cynomolgus monkeys, crotamiton socially subordinate females had increased cell proliferation and proportions of glandular and epithelial tissue, and less stroma in endometrium, and increased breast tissue thickness than their dominant counterparts (Shively et al., Jul–Aug 2004). These tissue characteristics are associated with increased risk of endometrial and breast cancer in women (Nucci et al., Mar 2003 and Ursin et al., Apr 2003). Socially dominant rhesus macaques live longer than their subordinate counterparts (Blomquist et al., 2011). Likewise, low social status is associated with increased mortality in the human population (Adler, Nov 2009 and Adler et al., Jan 1994). There is reason to believe that diet composition may modulate stress responses. For example, rats consuming a high fat diet have a higher cortisol response to stress compared to rats consuming a low fat diet (Legendre and Harris, Nov 2006). Likewise, chronic variable stress exaggerates the lipid response to a high fat diet (Manting et al., 2011). In clinical studies, consuming a high fat meal (mostly saturated animal fat) acutely exaggerates cardiovascular responses to stress (Jakulj et al., Apr 2007). Such responses have been shown to be attenuated in short term studies by consuming diets rich in polyunsaturated fats derived from plant sources (e.g.

50 The timing of EAA-rich protein consumption relative to the res

50 The timing of EAA-rich protein consumption relative to the resistance training bout may also play an important role in the anabolic response. Resistance training induces increased blood-flow and utilization of amino acids for muscle protein synthesis. Therefore,

milk-based proteins should be consumed in close proximity to the resistance training session.50 Also, the elderly, in comparison Inhibitors,research,lifescience,medical to the young, may require a greater amount of protein to achieve an anabolic response to resistance training. Yang et al.53 have reported that muscle protein synthesis in older adults is increased with ingestion of 40 g of whey protein, whereas in younger adults post-exercise rates of muscle protein synthesis are saturated with only 20 g of protein. The creatine/phospho-creatine energy system is used to sustain adenosine triphosphate (ATP) levels during times of Inhibitors,research,lifescience,medical high energy demand as in resistance training bouts.54 Previous studies have reported an age-associated reduction in skeletal muscle creatine/phospho-creatine.54 Rawson et al.54 Inhibitors,research,lifescience,medical reviewed the effect of creatine supplementation on skeletal muscle of

the elderly. They have reported that supplementation of creatine in older adults, in combination with resistance training, increases lean body mass, enhances fatigue resistance, increases muscle strength, and improves performance of activities of daily living to a greater extent than resistance training alone. Although reported to be a safe dietary supplement, the safety of creatine supplementation and its long-term benefits to the elderly population need to be further investigated before including it as a recommended Inhibitors,research,lifescience,medical strategy for the prevention and treatment of sarcopenia.54 In summary, to maximize

the benefits of exercise in older adults as a method to combat sarcopenia progression, adequate dietary intake is of great importance. This includes sufficient caloric intake and consumption of EAA-rich protein sources that would promote muscle anabolism, especially in Inhibitors,research,lifescience,medical older persons taking part in resistance training programs. ALCOHOL CONSUMPTION AND SKELETAL MUSCLE Alcohol misusers frequently suffer from low muscle mass and strength, muscle pain, cramps, difficulties in gait, and falls.55 This phenomenon is known as alcoholic myopathy.55 Acute alcoholic only myopathy occurs after severe alcoholic binges in malnourished alcoholics. It is a rare condition characterized by painful muscles, myoglobinuria, raised serum creatine kinase activities, and often renal impairment.55 However, chronic alcoholic myopathy is a common complication of alcoholism affecting approximately 50% of alcohol misusers.55 Chronic alcoholic myopathy is not associated with nutritional, vitamin, or mineral deficiencies or alcoholic liver disease, and it is reversible within 6–12 months of abstinence.

For example, people with osteoarthritis are more sensitive to exp

For example, people with osteoarthritis are more sensitive to experimental noxious stimuli at body sites distant from their

affected joints compared to people without arthritic pain (Farrell et al 2000, Imamura et al 2008, Lee et al 2011). Prolonged osteoarthritic pain is also associated with neurochemical, molecular and metabolic re-organisation in both the peripheral and central nervous systems (Farrell et al 2000, Bajaj et al 2001, Fernandezde-las-Penas et al 2009, Imamura et al 2008, Gwilym et al 2009, Im et al 2010, Mease et al 2011). These profound changes help to explain the diverse clinical manifestations of osteoarthritis, such as discordances between the degree of What is already known on this topic: People with osteoarthritis can experience local pain due to peripheral nociception, but recent research suggests they may also have generalised hyperalgesia. Among people with thumb carpometacarpal osteoarthritis, radial nerve mobilisation Nutlin-3a solubility dmso had local hypoalgesic effects. What this study adds: Selleck Cyclopamine Among people with unilateral thumb carpometacarpal osteoarthritis, radial nerve mobilisation also reduces pressure-pain thresholds in the contralateral hand, suggesting bilateral hypoalgesic effects. Interestingly, central sensitisation has been documented

in people with knee and hand osteoarthritis (Creamer et al 1996, Bajaj et al 2001, Farrell et al 2000, Imamura et al 2008). Bilateral hyperalgesia has been reported in the tibialis anterior muscle in people with unilateral knee osteoarthritis (Bajaj et al 2001). Injection of local anesthetic

in one knee was followed by pain relief in the contralateral, non-injected knee (Creamer et al 1996). Additionally, people with moderate to severe persistent knee pain have significantly lower pressure pain thresholds than controls (Imamura et al 2008). The role of central sensitisation mechanisms in maintenance and augmentation of upper extremity pain has been also studied in unilateral carpal tunnel (Fernandez-delas- Penas et al 2009) and lateral epicondylalgia (Fernandez-Carnero et al 2009), illustrating bilateral widespread pressure pain hypersensitivity, perhaps due to peripherally maintained central sensitisation. This sensitisation in both peripheral and central sensory neural pathways is believed to be relevant to the Thalidomide initiation and maintenance of persistent pain (Graven-Nielsen and Arendt-Nielsen 2002). An important feature of central sensitisation in osteoarthritis pain is hyperalgesia, often radiating far from the painful joint (Nijs et al 2009). Libraries Several studies indicate that manual therapies can induce mechanical hypoalgesia (Vicenzino et al 1996, Sterling et al 2001, Vicenzino et al 2001, Villafañe et al 2011a, Villafañe et al 2012a, Villafañe et al 2012b). This effect may be concurrent with sympathetic nervous system (Vicenzino et al 1996) and motor (Sterling et al 2001) excitation.

Clearly, this represents the particular challenge, underscores th

Clearly, this represents the particular challenge, underscores the importance of the analysis of gene-gene-environment, interactions, and implies that, potentially many different models of interactions will have to be explored. In this context, individual variation in drug response may involve any of the gene networks that are part of Inhibitors,research,lifescience,medical the complex interplay between specific disease-associated factors, pharmacokinetics, and pharmacodynamics.9,85-87,99 These may include any of the functional pathways involved in the specific pathophysiology of the

disease. Nonresponse may, for instance, be due to genetic heterogeneity in disease etiology. In this case, the drug may not, target the specific causative mechanisms active in the individual.87 Moreover, the gene encoding the specific drug target, represents the

first, Inhibitors,research,lifescience,medical component, of an entire downstream pathway that controls signal transduction and elicits the cellular effects. Thus, genetic variation in any of the genes regulating this pathway may cause variation in drug response. Furthermore, numerous genes or gene families are involved in drug transport and drug metabolism, such as the genes encoding the phase I and phase II enzymes, which Inhibitors,research,lifescience,medical are expressed in the liver.9,12,85-87,99 In addition, Inhibitors,research,lifescience,medical environmental factors, such as nutrition, exercise, access to substances of abuse, etc, may influence drug response. In the future, progress in the understanding of the molecular bases of disease and drug response is expected to come especially from advances in functional genomics as the basis for whole complex systems analysis. These advances will be based on the increasing elucidation of the function of all genes involved in all pathways constituting the relevant process. In this new approach to biological research, the same type

of Icotinib cost analyses, which are Inhibitors,research,lifescience,medical typically used to try to understand the function of single genes, are carried out on most, or all genes of the organism. Enormous amounts of information on the networks of biological processes are being generated, leading to the establishment Oxymatrine of models of specific functional networks. Apart from deriving many novel candidate genes and drug targets of interest, this may provide yet another approach to group multiple variants in genes, in which according to functional context, the model is used as a template for classification and functional interpretation of a spectrum of gene variants. Thus, systems analysis can be extended to pose the question of whether a specific metabolic pathway involving many genes of variable variability could be involved in a specific phenotype or disease.

With more than 32,000 patients evaluated, the CCR has never miss

With more than 32,000 patients evaluated, the CCR has never missed a single injury resulting in spinal

cord injury. Nevertheless, we have included the SCH772984 chemical structure following strategies to maximize the safety of this study: 1. We have re-designed the new proposal to include only a single centre to focus on safety and efficacy. 2. The single site proposed for this study also participated in the paramedic validation study. 3. Paramedics will only participate Inhibitors,research,lifescience,medical in this study if they: • have completed a 2-hour training session and, • pass a written test. 4. Paramedics will use the CCR under a medical directive signed by the Ministry of Health. 5. We will have an independent Data Safety Monitoring Committee review results on a regular basis; that committee will have the authority to recommend termination if patient safety is a concern. Ethical Considerations The study protocol received the approval of The Ottawa Hospital Inhibitors,research,lifescience,medical Research Ethics Board (protocol #2009142-01H) without the need for written patient consent. Paramedics will use the CCR under a medical directive, making training and participation in the study mandatory. Because of this, Inhibitors,research,lifescience,medical the Research Ethics Board also waived the need for paramedic consent. During a particular period in

time, all eligible patients will be managed by the paramedics in the same manner in this observational cohort study. Patients will not be randomized. Patients will not be subjected to new therapy, invasive procedures, undue risk or discomfort, or investigations beyond that which would normally be required in the course of patient care. Patient confidentiality will be maintained throughout Inhibitors,research,lifescience,medical the study and patient names will be removed from all records. This is consistent with the approach approved by the Research Ethics Boards for our previous physician, ED triage nurse, and paramedic validation and implementation studies. Study interventions Training Initial training for all paramedics will entail one hour of self-review of a teaching CD, followed by a short quiz, followed by an

in-person presentation of scenarios Inhibitors,research,lifescience,medical and question ADP ribosylation factor and answer. The teaching CD includes continuous audio and video presentation of slides on evidence and application, questions and answers, and case studies. All paramedics will have to successfully complete a written test in order to be certified in c-spine assessment. Run-in period This phase will allow the paramedics to fully clear the c-spine of low-risk patients. The purpose of the run-in period is to provide pilot experience with clearance and removal of immobilization in order to identify any logistical or unforeseen barriers. This run-in period is necessary since it will represent the first time that paramedics have actually not immobilized low-risk trauma victims in Ottawa, and we wish to proceed cautiously prior to enrolling cases for the study analysis.