More importantly, a subset of these regions, including the right

More importantly, a subset of these regions, including the right medial frontal gyrus, thalamus, ACC, left ventral striatum, and OFC, exhibited significant reward cue by target interactions. These results suggest that potentially rewarding trials (e.g., reward cues) are associated with lower activation

in attentional networks during following targets, possibly due to increased efficiency. In contrast, non-reward trials with high probability for money loss (e.g., non-reward cue followed by incongruent/most difficult targets) appear associated with higher activity in attentional networks indicating possible compensatory efforts to avoid punishment. In addition, Inhibitors,research,lifescience,medical these trials were also associated with lower

activity in regions of the motivational system, suggesting that they may be experienced as less rewarding. Acknowledgments The author would like to acknowledge Dr. Jeffrey Schwartz for his contrubution to this work. Conflict of Interest None declared. Supporting Information Additional Supporting Information may be found Inhibitors,research,lifescience,medical in Inhibitors,research,lifescience,medical the online version of this article: Table S1. Instruction for subjects. Click here to view.(27K, doc) Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting DAPT secretase mechanism materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.
Guanosine 3′,5′-cyclic monophosphate (cGMP) is an intracellular second messenger that is synthesized in response to the activation of either soluble guanylyl

cyclase by nitric oxide (NO) (Miki et al. 1977; Chinkers and selleck kinase inhibitor Garbers 1991) or the membrane-bound guanylyl cyclase GC-B primarily by the C-type natriuretic Inhibitors,research,lifescience,medical peptide (CNP) (Potter et al. Inhibitors,research,lifescience,medical 2006). Cyclic GMP effects are predominantly mediated by the activation of cGMP-dependent protein kinases (PKGs). Two distinct mammalian PKGs, PKG-I and PKG-II, have been identified, as well as two splice variants of PKG-I (PKG-Iα and -Iβ). Both PKG-I and -II are found in the brain; PKG-I is highly expressed in cerebellar Purkinje cells and, to a Anacetrapib lesser extent, in striatal medium-spiny neurons (Lohmann et al. 1981; Ariano 1983; DeCamilli et al. 1984; Jarchau et al. 1994). PKGs are implicated in various aspects of brain physiology, including development (Guan et al. 2009), neurotransmitter release (Guevara-Guzman et al. 1994; Lin et al. 1995), and synaptic plasticity (Zhuo et al. 1994). Alteration of gene expression in response to drugs of abuse is thought to underlie the persistent behavioral changes associated with chronic use (Nestler 2001). Epigenetic mechanisms that regulate the accessibility of genes to the transcriptional machinery in the mature brain control changes in gene expression produced by cocaine (Colvis et al. 2005; Cassel et al. 2006).

The operator then measures the overlap

distance of the tw

The operator then measures the overlap

distance of the two valves to better understand the position of the second valve that will be implanted. Certain steps can be taken to improve the accuracy of implantation. While focusing on the distal (inflow) aspect, the operator can release the second valve until it is one-third deployed, then focus on the proximal (outflow) aspect of the second valve and determine the optimal distance between the frame Inhibitors,research,lifescience,medical loops of the first and second valves. For this part it is important not to focus on the distal aspect (inflow) of the valves, because the “criss-cross” appearance of the struts will make it difficult to differentiate the individual valve frames. Once optimal distance between the outflow tips is determined, the operator can deploy the remainder of the valve while strictly maintaining the prescribed distance

between the two frames. After complete release of the second valve, it is likely that there will be no significant AR observed and, as a result, no need for balloon Inhibitors,research,lifescience,medical aortic valvuloplasty (BAV) post-implantation. Inhibitors,research,lifescience,medical When AR (grade ≥2) is observed, or when tortuous anatomies challenge the implantation of the second valve, the operator should assess for incomplete expansion and axialization of the second valve’s frame using control TEE or rotational fluoroscopy. If this is confirmed, BAV post-implantation should be considered High Implantation With the possibility of full valve retrieval up to four-fifths of the way through the deployment process, such a situation should rarely occur except in cases of technical mistakes during the last steps of the procedure. Inhibitors,research,lifescience,medical Examples include (A) www.selleckchem.com/products/Y-27632.html failure to notice incomplete disengagement of both frame loops from the delivery catheter before withdrawing the catheter; (B) Inhibitors,research,lifescience,medical failure

to manage the distal tip of the delivery catheter (i.e., nose cone) through the prosthesis after successful valve deployment, resulting in tip displacement of the valve frame; (C) post-implant dilatation without the use of rapid pacing, or rapid pacing terminated too early relative to balloon inflation, resulting in ejection of the balloon-valve unit into the ascending aorta. Unfortunately, a high implantation does not offer the same attractive options for correction as a low implantation. However, it is important to first clearly define the criteria for acceptable parameters Batimastat despite a “too-high” implantation. To a certain extent, the sealing effect of the native calcified aortic valve around the frame (similar to a chimney above the annulus) can make a “too-high” implantation perfectly compatible with a good result, with no to mild or moderate AR. The control angiogram and the hemodynamic blog post analysis provide the criteria for an acceptable result: (1) AR grade ≤2; (2) no ventricular-aortic gradient; and (3) no coronary occlusion.

That is, it is a quantification of the rule that determines how a

That is, it is a quantification of the rule that determines how a BAY 734506 choice is made. When response bias shifted to a relatively more liberal bias, that is, the decision criterion changed, increased activation was observed in the left IFG. This seems to be in line with the aforementioned findings from Crone and colleagues (Crone et al. 2006) who observed an increase in activity in this region when the rule used to make a choice needed to be changed. Previous studies investigating the

sellckchem neural correlates of perceptual decision-making have implicated the left SFS in the computation Inhibitors,research,lifescience,medical of perceptual decisions (Heekeren et al. 2004, 2006; Pleger Inhibitors,research,lifescience,medical et al. 2006; Philiastides et al. 2011). For example, Heekeren and colleagues (Heekeren et al. 2006) found that activation in

the left superior frontal sulcus reflected the comparison of accumulated evidence needed for the discrimination of perceptual stimuli. When activity in this region was disrupted, the rate of sensory Inhibitors,research,lifescience,medical evidence accumulation decreased and decisions became less accurate (Philiastides et al. 2011). While the left SFS may be involved in comparing sensory evidence, we (Reckless et al. 2013) previously found that a more ventral region of the frontal cortex, the left IFG may be involved in adjusting the decision criterion between different decision environments. Inhibitors,research,lifescience,medical However, the block design of that study limited how this

relationship could be interpreted. The present findings suggest that the left IFG is indeed involved in adapting the decision criterion. This is in keeping with findings from Rahnev and colleagues (Rahnev et al. 2011) who found that individuals who adjusted their response bias more based on information from predictive cues had greater activation in the left IFG. However, Inhibitors,research,lifescience,medical one problem that arises when considering results across perceptual decision-making studies is whether the perceptual decision-making task was one of detection or one of discrimination and what decision-making model was used to evaluate the behavioral Dacomitinib and imaging findings. This study used a detection task and signal detection theory (SDT). Rahnev and colleagues (Rahnev et al. 2011), who found a similar relationship between response bias and activation in the left IFG, used a discrimination task and SDT. The finding that there is a relationship between response bias and the left IFG in both a discrimination and a detection task suggests that the relationship is independent of the type of perceptual decision-making task performed. A limitation of this study was that it used one theory of decision-making to investigate the neural correlates of the decision criterion.

In 2001, Saito et al (25) evaluate the efficacy of oral carvedi

In 2001, Saito et al. (25) evaluate the efficacy of oral carvedilol (10.1-40.3 μg/kg/day) for 6 months in 4 DMD patients who had elevated plasma atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP), and a low ejection fraction (EF< 40%) in echocardiography. The values did not change significantly compared with controls. Clinical symptoms also did not change in either group. Inhibitors,research,lifescience,medical They conclude that carvedilol therapy did not change the left ventricular dysfunction in DMD. However carvedilol therapy can be safe for patients with dilated

cardiomyopathy associated with muscular dystrophy, even producing a modest improvement in systolic and diastolic function (26). Combination of therapy It has been reported that the Inhibitors,research,lifescience,medical combination of an ACEinhibitor and a beta-blocker has additive effects in patients with congestive heart failure. Such an approach has been extended to Duchenne muscular dystrophy patients with left ventricular dysfunction in order to assess AZD-2281 whether this combination was associated with long term survival of DMD patients with dilated cardiomyopathy. In 1999, Ishikawa et al. (27) reported the effectiveness of the combination of Inhibitors,research,lifescience,medical ACEI and beta-blockers in 11 DMD patients with symptomatic heart failure for relief of symptoms and decrease of activated neuroendocrine

level during 5-year Sorafenib B-Raf follow up. In 2006, Kajimoto et al. (28) confirmed the beneficial effects of the association beta-blocker carvedilol/ACEI on ventricular function in Inhibitors,research,lifescience,medical 13 patients with muscular dystrophy compared with the ACEI only. In fact the combination therapy of carvedilol and an ACEI for 2 years resulted in a significant increase in left ventricular fractional shortening (LVFS), while in the ACEI group, there was no significant change in LVFS. Left ventricular enddiastolic dimension increased in the

ACEI group, but not in the carvedilol/ACEI group. Ten years later, Ogata et al. (29) studied the long term efficacy Inhibitors,research,lifescience,medical Cilengitide of an ACEI and a beta-blocker in 52 DMD patients with reduced LVEF, with [12] or without [40] symptoms of heart failure. They showed that 5-year and 7-year survival rates of symptomatic patients were 81 and 71% respectively. Survival rate became 0 at 10,9 years. In the prevention group (asymptomatic patients) 5- and 7-year survival rates were 97 and 84% respectively, and 10-year survival rate was 72%. The beneficial effects of the combined ACEIs and beta- blockers therapy has been observed in DMD patients, with both gene deletions or point-mutations (30). Recent papers (31, 32) confirm that the use of ACEIs and beta-blockers in patients with DMD reverse congestive heart failure signs and symptoms, delay regression of left ventricular disfunction and improve systolic function.

1998) is a short structured diagnostic interview, developed joint

1998) is a short structured diagnostic interview, developed jointly by psychiatrists and clinicians in the United States and Europe for DSM-IV and ICD-10 (International Classification of Diseases) psychiatric disorders. With an selleck kinase inhibitor administration time of approximately 15 min, it was designed to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials, epidemiology studies, and as a first step in outcome tracking in nonresearch clinical settings. Crane and colleagues (2007) argued that MINI is appropriate

for use in experimental Inhibitors,research,lifescience,medical studies because it requires much less time than the Structured Clinical Interview for the DSM-IV (SCID; First et al. 1996). The Chinese version of the MINI was translated by the Taiwanese Society of Psychiatry (Si et al. 2009). The BDI-II (Beck et al. 1996) is a commonly used assessment of the severity of depression. It is a 21-item self-report inventory measuring the Inhibitors,research,lifescience,medical affective, cognitive, and physical symptoms of depression. The Chinese version was translated by the Chinese Behavioral Science Corporation (2000). A few studies have shown that the BDI-II is a valid and reliable assessment tool for Chinese populations (Yeung et al. 2002; Byrne et al. 2004). Procedure Each blog of sinaling pathways patient was assessed with the MINI, followed by the BDI-II, to evaluate the severity of her current depressed mood. Healthy Inhibitors,research,lifescience,medical controls took only the BDI-II as a preliminary

screening. The study was conducted one-to-one in a quiet room at the hospital. Participants then

Inhibitors,research,lifescience,medical sat in front of a computer, which delivered the experimental task. To make the participants believe that they were playing with real people, a cartoon lasting about 10 sec was presented before the task that informed the participant that the experimental computer was in the process of connecting with the server and the investor. The task lasted about 30 min. Participants were debriefed after the experiment to confirm that they had been actively participating. Data analysis Trials with reaction times exceeding three standard deviations of the mean were excluded. The number of trials excluded Inhibitors,research,lifescience,medical was less than 5% of the total trials in each condition for each participant. Repeated-measures analyses of variance (ANOVAs) were then used to analyze the reaction time for all responses, frequencies of deceptive and altruistic responses, and the ratios of deceptive to altruistic responses. The ANOVAs included two within-subject factors: the repayment proportion (R, three AV-951 levels: 20%[low], 50%[equal], and 80%[high]) and the probability that the investor would detect the trustees’ repayment amount (P, two levels: 25%[low] and 75%[high]). The differences between the two groups (patients with depression and healthy participants) were then analyzed by between-subject comparison. Results Frequency of choice for deceptive responses Patients with depression made deceptive responses less frequently (0.25 ± 0.29) than the healthy participants (0.37 ± 0.

228,230 Relatively less attention has been given to bipolar disor

228,230 Relatively less attention has been given to bipolar disorder, despite its severity. However, there have been findings of altered induced responses in the β and γ bands.231-253 In alcoholic patients (after long abstinence from alcohol), resting β is increased, α is low in certain seriously subsets, α-band interhemispheric coupling is greater, γ is decreased in visual tasks, and evoked responses are less.234 Attention-deficit hyperactivity disorder patients have been consistently found to have increased

frontal θ power and increased γ-β ratio compared with controls,35 γ power in response to auditory stimuli have also been found to be increased.236 Abnormalities of α and Inhibitors,research,lifescience,medical β rhythms have also been found in personality-disordered Inhibitors,research,lifescience,medical patients.237-239 Patients with autism spectrum disorders (ASD) also have remarkably altered EEG/MEG patterns, often time characterized by “disorganized” but high γ power and reduced rhythm.211,240-242 Advancing disease understanding We believe that, while investigation of oscillations in the brain can also deepen our understanding of the pathophysiology of mental disease, progress has been disappointingly slow, with discoveries of new psychotherapeutic drugs practically at a standstill, and development of homologous relevant animal models being extremely challenging.243 Working under the principle

that cognition Inhibitors,research,lifescience,medical and perception are supported by brain-generated ensemble patterns in cortical networks

and that impairment of proper temporal organization underlies the various deficits associated with psychiatric and neurological disorders, then studying network Inhibitors,research,lifescience,medical oscillations should be an effective and novel method for both furthering our understanding of the basis of neuropsychiatry Inhibitors,research,lifescience,medical disease and for finding new treatments. Network oscillations have a combination of properties, which allows them to be particularly appropriate targets for further mechanistic and therapeutic research. First, as discussed above, network oscillations are robust pheno types whose general properties are well preserved throughout mammalian evolution. Second, rhythms vary within a small but reliable range from individual to individual in a manner that has been born out by data to relate to function and disease. Third, on a shorter time scale oscillations are strongly influenced Drug_discovery by both overt and cognitive behaviors. Fourth, different rhythms are specific to particular brain structures and, finally, they have the right temporal scale for the assessment of cell assembly patterns. These features, when combined, suggest that reliably measurable selleck chemicals signals correlating with specific disease and functional impairment can be detected in specific regions of the brain in response to specific behaviors and stimuli and can be reliably studied in animals to further our understanding, with an aim towards novel therapeutics.

For example, one study evaluated 978 patients with mild-to-modera

For example, one study evaluated 978 patients with mild-to-moderate AD treated with slow dose escalation of galantamine.24 After 4 weeks of placebo, patients were randomized to one of four treatment groups: research only placebo or galantamine escalated to final doses

of 8,16, or 24 mg/day. At 5 months, both the 16 and 24 mg/day groups showed very little change from baseline, while the placebo group scores deteriorated. As a result, the 16 and 24 mg/day groups exhibited significantly better NPI total scores as compared to placebo (P<0.05). Improvements were also seen in the ADASCog and CIBIC-plus in the 16 and 24 mg/day groups.24 Combination therapy: rationale, Inhibitors,research,lifescience,medical efficacy, and safety A potential treatment regimen may be developed based on the stages of AD. The latent stage, which may last for several decades, exists among individuals at known genetic risk of late-life AD.2-5 These patients may show changes in functional abilities, early neuroanatomic Inhibitors,research,lifescience,medical changes, and regional hypometabolism in temporal and parietal lobes in their middle life.25 During this stage, neuroprotection with NSAIDs, NMDA receptor antagonists, and estrogen may slow or attenuate progress and prove beneficial. During the prodromal stage, early cognitive symptoms appear, and as damage increases substantial impairment develops.25 Inhibitors,research,lifescience,medical Treatment interventions in this stage may slow

table 1 progression from mild symptoms to disabling dementia. Cholinesterase inhibitors may work best at this stage of the disease. During Inhibitors,research,lifescience,medical the symptomatic stage, the goal is to improve existing cognitive functions and prevent current symptoms from worsening.25 Medications that may be beneficial during this stage include Ginkgo biloba, NMDA receptor antagonists, antipsychotics, and antidepressants. Treatment strategies for the immediate Inhibitors,research,lifescience,medical future should include therapy with some or all of the following compounds: acetylcholinesterase inhibitors, Ginkgo biloba, NSAIDs, NMDA receptor antagonists, atypical antipsychotics, and SSRIs. One study is currently investigating whether the concurrent use of an atypical antipsychotic (risperidone, olanzapine,

or quetiapine) and galantamine increases the incidence of adverse events associated with either class Carfilzomib of drug.26 Subjects from the following multicenter, double-blind, placebo-controlled studies of galantamine in the USA were included: GAL-USA-1 and GAL-USA-10. Only the subjects that were cither on galantamine 16 or 24 mg, or placebo were included. Subjects who used conventional antipsychotics and subjects who took atypical antipsychotics only during screening were excluded. Specific adverse events outcomes included the following: falls, peripheral edema, rhinitis, somnolence, urinary tract infection, and extrapyramidal symptoms. These adverse events have been described in previous studies of atypical antipsychotic treatment in older adults.

Since the stabilization exercises exerted a minimal load on the s

Since the stabilization exercises exerted a minimal load on the spinal column, it can be regarded as an important clinical approach to curing acute LBP in rehabilitation centers. These exercises are

used to strengthen the muscles affecting the spinal stabilization system. In addition, the present study demonstrated that the muscle activation in arm extension was less than that in the bird-dog position. As was mentioned before, in the bird-dog position, the body is unstable and patients with weak muscles are not able to tolerate this exercise. Thus, arm extension, which has not been investigated in the previous studies, can be deemed the starting stage of quadruped exercises before Inhibitors,research,lifescience,medical progress to the bird-dog exercise. Oliveira27 also suggested the progression of exercises from simple to complex because of the high demands of muscle activation during complex exercises. For the all the Inhibitors,research,lifescience,medical research hitherto reported in the existing literature, comparison should be made between LBP patients and healthy individuals to shed further light on the subject. Conclusion

In the four-point kneeling position performed by our healthy subjects, all the muscles responsible for core stability seemed to work in harmony. Ruxolitinib However, in the different positions, as loads were applied to the spine and the bases of support were changed, muscle activation was altered in order to balance Inhibitors,research,lifescience,medical the stability and demands of the movements. Acknowledgment The present article was extracted from a thesis written by Farahnaz Emami and was financially supported by Shiraz University of Medical Sciences, Shiraz, Iran (Grant No. 692). Hereby, the authors would like to thank Dr. Motealleh for his technical assistance and Ms. A. Keivanshekouh for her linguistic assistance. We would also like to Inhibitors,research,lifescience,medical thank the Research Improvement Center, Shiraz University of Medical Sciences, Shiraz, Iran. Conflicts of Interest: None declared.
Background: Unlike Inhibitors,research,lifescience,medical the western hemisphere, information about stroke epidemiology in southern Iran is scarce. The aim of this study was to determine the main epidemiological characteristics of patients with stroke and its mortality Carfilzomib rate in southern Iran.

Methods: A retrospective, single-center, hospital-based longitudinal study was performed at Nemazee MG132 solubility Hospital in Shiraz, Southern Iran. Patients with a diagnosis of hemorrhagic and ischemic strokes were identified based on the International Classification of Diseases, 9th and 10th editions, for the period between 2001 and 2010. Demographics including age, sex, area of residence, socioeconomic status, length of hospital stay, and discharge destinations were analyzed in association with mortality. Results: 16351 patients with a mean age of 63.4 years (95% CI: 63.1, 63.6) were included in this analysis. Men were slightly predominant (53.6% vs. 46.4%). Forty-seven percent of the total sample was older than 65,17% were younger than 45, and 2.6% were children younger than 18.

Brain oscillations provide framework for a neural syntax Most, if

Brain oscillations provide framework for a neural syntax Most, if not all, network oscillations are based on inhibition wherein populations of principal neurons are paced by repetitive trains of inhibitory postsynaptic potentials. These rhythmic inhibitory volleys provide windows of alternating reduced and enhanced excitability of principal cells in a temporally coordinated manner.17,45 Indeed, segregation of excitatory principal cells into functional groups, often referred to as cell assemblies and assembly sequences,46 is perhaps the most important service performed by the

large family of inhibitory neuron classes Inhibitors,research,lifescience,medical in the cortex.47,48 Inhibition-based oscillations may do so by providing a natural means to “stop” signals of neuronal information flow by temporally silencing principal cells and “chunking” selleck chemicals Axitinib streams of messages into shorter frames, as evidenced by the observation that oscillations have well-defined Inhibitors,research,lifescience,medical onsets and offsets with characteristic Inhibitors,research,lifescience,medical maximum and minimum spiking activity in the information-transmitting principal

cells.49 This stop-start parsing function of neuronal oscillators and their hierarchical cross-frequency coupling organization (see section below as well as Figure 2), in turn, can support syntactical rules, known to both sender and receiver, making communication Inhibitors,research,lifescience,medical more OSI-744 straightforward than interpreting long

uninterrupted messages50 or stochastic patterns of spikes. In general, syntax is a set of principles that allows the generation of rich combinations from a limited number of elements using a minimal number of rules. It has been hypothesized that the Inhibitors,research,lifescience,medical fundamental element of neuronal syntax is an assembly of neurons discharging together in a γ cycle.51-53 The most important role of the cell assembly is to bring together sufficient numbers of peer neurons so that their collective spiking can bring above discharge threshold the proper population of downstream postsynaptic neurons.52 Consequently, from the point of view Anacetrapib of the downstream (“reader” or “integrator”) target cells, collective activity of upstream neurons is classified as a single event53 only if their spikes occur within the time-integrating window (ie, within the membrane time constant of the neurons, tends to be 10 to 30 msec; if signals occur within this time scale, they will be combined as a unitary event).54 Spikes of upstream neurons which fire outside the integration time window must be part of another event, or a separate assembly.

Comparison of the results of this study with an evidence-based mo

Comparison of the results of this study with an evidence-based model of VM performance (Table ​(Table4)4) demonstrated that the introduction of such a model would undoubtedly improve the standard of care provided to patients with haemodynamically stable SVT by MICA Paramedics through compliance with a means of maximising the effect of vagal manoeuvres in the prehospital setting. Of interest is that the results obtained demonstrate a trend toward a higher Inhibitors,research,lifescience,medical compliance

to individual elements of an evidence-based model than a previously studied emergency physician cohort [2], suggesting the potential for this model to be incorporated into the wider primary care field for the management of SVT. This study is potentially limited by the small sample size. The influence of cultural and individual learning to provide a higher than expected

compliance with the evidence-based model is not quantifiable within this study, however further studies may be able to differentiate chance from Inhibitors,research,lifescience,medical acquired knowledge, and hence eliminate this potential limitation. The ability to generalise these results to the operational MICA Paramedic population in Victoria http://www.selleckchem.com/products/Y-27632.html should be undertaken with caution as these results may not be a true representation of the total Victorian operational MICA Paramedic population. Conclusion This study has highlighted a need to Inhibitors,research,lifescience,medical broaden and standardise the education of VM, through the promotion of an evidence-based model of practice, selleck chem inhibitor across the spectrum of primary emergency health care disciplines. At present, it would appear there is little scientific evidence utilised in the education of MICA Paramedics Inhibitors,research,lifescience,medical with regard to vagal manoeuvres and the reversion of SVT. This study has specifically identified the need for an evidence-based approach

to the education of student MICA Paramedics, and a continuing Inhibitors,research,lifescience,medical education program for qualified MICA Paramedics, in the biomechanics and processes involved in terminating SVT in order to improve patient care. Competing interests The authors declare that they have no competing interests. Authors’ contributions GS conceived the study and undertook the data collection. Both authors devised the study methodology. Dacomitinib MB undertook the statistics and both authors compiled the manuscript. Both authors have read and approved the manuscript. Pre-publication history The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-227X/9/23/prepub Acknowledgements We wish to acknowledge the MICA Paramedics who gave their time for the study.
The demand for emergency medical services is increasing in industrialized countries [1-5]. In many countries, ambulance responses are tailored to give priority to true emergency calls and thus save the lives of patients suffering from serious conditions.