This review focuses on the use of iPSCs in cardiovascular medicine. The Promise of iPSCs for Cardiovascular Medicine: a Comparison to Other Stem Cell Sources A stem cell is defined by its capacity for both self renewal and directed differentiation. There are three broad categories of stem cells for application in regenerative medicine: iPSCs, embryonic stem cells (ESCs), and adult stem cells. The ESC is derived Inhibitors,research,lifescience,medical from the inner cell mass of the fetal blastula and is pluripotent, i.e., it is able to

differentiate into any cell type of the adult body. ESCs can replicate via mitotic division while retaining their undifferentiated state (self-renewal) or differentiate into lineage-specific cells under the appropriate stimuli. ESCs

can theoretically be used to create any tissue in the body for the purpose of regenerative medicine. Indeed, clinical trials are currently underway using these cells. However, a cell lineage or tissue created using Inhibitors,research,lifescience,medical ESCs will be immunologically distinct from the host, requiring immunosuppression. This concern may be partially addressed by creating banks of ESCs that would be matched for major histocompatibility Inhibitors,research,lifescience,medical antigens to recipients. However, ethical concerns have been voiced in using ESCs because they are derived from early human embryos. By contrast, there are no such ethical concerns with the use of adult stem cells. These cells are multipotent rather than pluripotent; in other words, they partially lineage-committed, typically giving rise only to cells of a given germ layer. These multipotent cells are found in the bone marrow, the circulation, and within most tissues. Because they can be harvested from an individual and expanded ex vivo, they do not need to overcome an immunologic barrier. Inhibitors,research,lifescience,medical Recent preclinical and clinical studies indicate that some common sources of stem cells—including hematopoietic stem cells, endothelial progenitor cells, cardiac stem cells, mesenchymal stem cells, or adipose stem cells—may reduce infarct size and improve cardiac Selleck PD98059 contractile function in patients with myocardial infarction.1-3 Inhibitors,research,lifescience,medical These beneficial effects are modest in humans and thought to be due largely to paracrine

effects of secreted factors from the adult stem cells rather than the incorporation of the cells into the affected tissue. In addition to the limited MTMR9 (if any) benefit of adult stem cell therapy, there are significant drawbacks compared to pluripotent stem cells such as ESCs or iPSCs. Adult stem cells are limited in their differentiation potential and replicative capacity; in other words, they can only give rise to a limited set of cells, and they have a limited number of population doublings before they senesce. Furthermore, in the case of autologous adult stem cells, the conditions that give rise to cardiovascular disease (e.g., hypercholesterolemia, aging, or tobacco exposure) are known to decrease their number and function.

The aim in palliating patients with malignant GOO is to re-establish an oral intake by restoring gastrointestinal continuity. This ultimately improves patients’ quality of life in

the advanced stages of cancer. Traditionally, surgical gastrojejunostomy (GJ) has been the standard treatment approach for these patients. find more Although GJ relieves symptoms in almost all patients, the procedure is associated with morbidity of 10-16% and mortality of up to 7% (3-5). Also, post-operatively, most patients suffer delayed gastric emptying that is often associated with longer hospital stay (6). Although laparoscopic Inhibitors,research,lifescience,medical GJ has been introduced as a less invasive alternative to open GJ, the technique still carries substantial risk and is not widely available (7-10). Endoscopic placement Inhibitors,research,lifescience,medical of self-expandable metal stents (SEMSs) has emerged as an alternative means for palliation of GOO. Multiple uncontrolled case-series studies have demonstrated SEMSs to be safe

and effective with technical success of 90-100% and clinical success of 67-100% (11-17). Randomized trials have shown mixed results, with two trials Inhibitors,research,lifescience,medical favouring endoscopic SEMS (18,19) and one favouring surgical GJ (20). Therefore, it is currently unknown whether patients with GOO are best palliated with endoscopic SEMS placement or GJ. Also, SEMS are expensive and it is unclear whether their use is less costly when compared with surgical GJ. Although direct cost studies have shown that SEMS placement is less Inhibitors,research,lifescience,medical costly than surgery, the general applicability of the data is debatable given the small number of patients enrolled in each of these single-institution trials (7,21,22). Hence we performed this meta-analysis to compare outcomes of endoscopic stenting (ES) with GJ. The primary goal of this study is to the

compare the overall complication rate and effectiveness (ability to tolerate oral intake) of SEMS and GJ in patients with GOO. The secondary objective is to identify predictors of clinical outcomes [reintervention Inhibitors,research,lifescience,medical rate, length of hospital stay (LOHS), hospitalization charges, and complications]. Methods Study protocol We followed the Preferred unless Reporting Items for Systematic reviews and Meta-Analyses PRISMA guidelines where possible in performing our systematic review (23). We performed a systematic search through MEDLINE (from 1950), PubMed (from 1946), EMBASE (from 1949), Current Contents Connect (from 1998), Cochrane library, Google scholar, Science Direct, and Web of Science to January 2013. The search terms included “gastric outlet, gastroduodenal or duodenal obstruction’’, ‘‘gastrojejunostomy, gastroenterostomy or surgical bypass’’, and ‘‘endoscopic and stent”, which were searched as text word and as exploded medical subject headings where possible. No language restrictions were used in either the search or study selection. The reference lists of relevant articles were also searched for appropriate studies. A search for unpublished literature was not performed.

However, recent, evidence from imaging studies lends further support for a positive benefit of estrogen on cognitive functioning. In cortical regions typically hypometabolic in AD, Ebcrling et al221 found that older women who had never taken estrogen exhibited metabolic

ratios intermediate to those of AD patients and women on ERT. Similarly, a longitudinal Inhibitors,research,lifescience,medical assessment of regional cerebral blood flow changes observed increased flow over time in estrogen users compared with nonusers, particularly in the hippocampus and temporal lobes.222 Since the decision to take ERT may be impacted by education and socioeconomic variables, randomized clinical trials are needed to systematically address the merits of estrogen for cognitive processing in older women. To date, there have been a limited number of randomized clinical trials of estrogen use in healthy individuals, with the majority short-term in duration and often investigating younger adults.215,223 Inhibitors,research,lifescience,medical Data from large, long-term, randomized clinical trials in this population

are required before we can adequately assess the long-term benefits of estrogen use on cognition as well as its role in AD prevention. Neuronal degeneration Several clinical trials with nootropics, such as piracetam, have been conducted in older adults, and Inhibitors,research,lifescience,medical a significant positive impact of piracetam on both memory and attentional functions was observed.224-226 Additionally, two

studies have investigated the affect, of 4.8 Inhibitors,research,lifescience,medical g/day of piracetam on the driving ability of elderly adults exhibiting deficits in psychomotor speed at, baseline. While some investigators found that treatment with piracetam reduced the numbers of errors committed in real traffic, still others observed no benefit of piracetam on driving performance.62,227 The few studies conducted with pramiracetam in this population Inhibitors,research,lifescience,medical have also observed improvements in memory performance relative to placebo.228,229 Nonpharmacological treatments for normal aging Memory training Studies those from several groups including our own have documented the efficacy of providing cognitive training aimed at instructing older adults to use mnemonics for practical problems such as recall of names, faces, and lists. 230-234 However, some have criticized such interventions because the effects demonstrated have often been modest and shortterm.235 Furthermore, only a few studies have examined whether the benefits of memory training programs persist for longer periods and these have yielded mixed results.236-238 Additionally, it is unclear whether or not, Protein Tyrosine Kinase inhibitor subjects continue to employ the mnemonic technique acquired and whether this reported use of the mnemonic affects memory function. Several investigators found that at follow-up subjects had ceased to apply the mnemonic techniques acquired.

In both diseases, affected muscles show a high number of central selleckchem nuclei and a markedly increased variation in fiber diameter that commonly ranges

from less than 10 μm to greater than 100 μm (Fig. 2A, D). Basophilic regenerating fibers, splitting fibers, fibrosis and adipose deposition occur in both diseases to a variable degree depending on the extent of muscle involvement. Ring finger fibers and sarcoplasmic masses are generally more frequent in DM1 muscle biopsy. Recently the comparison of muscle biopsy findings in classic DM1 with those in DM2 has indicated that specific features are present in DM2 muscle biopsy helping the diagnosis of DM2. Inhibitors,research,lifescience,medical Severely atrophic fibers with pyknotic nuclear Inhibitors,research,lifescience,medical clumps similar in appearance to the severely atrophic fibers in neurogenic atrophy are frequently found in DM2 biopsy also before the occurrence of muscle weakness (Fig. 2D). In DM1, nuclear clumps are present in end-stage muscle biopsy (88). A predominant type 2 fiber atrophy in contrast

to the type 1 atrophy observed in DM1, has been described in DM2 (87, 89, 90, 91) (Fig. 2B,C,E,F). Moreover, in DM2 muscle biopsy central nucleation selectively affects type 2 fibers and the atrophic nuclear clumps express fast myosin isoform (type 2 fiber) Inhibitors,research,lifescience,medical indicating that DM2 is predominantly a disease of type 2 myofibers (90) (Fig. 2F; Table 3). Figure 2. Panel showing muscle histology in DM1 and DM2. A-C. Transversal sections from DM1 muscle biopsies. A. Haematoxylin & Eosin: fiber size variation and central nuclei (arrows) are present. B, C. The population of atrophic fibers (white arrow)

are … Table 3. Muscle histopatology in DM1 and DM2. Management In general the management of DM2 is similar to Inhibitors,research,lifescience,medical that of DM1, but there is less need for supportive care, such as bracing, scooters, or wheelchairs. Cataracts require monitoring. Cardiorespiratory disorders are responsible for 70% of the mortality in DM1 and many of these patients could have been treated by active monitoring and a lower threshold Inhibitors,research,lifescience,medical for input. Disturbances in cardiac rhythm are less frequent in DM2, but abnormalities do occur (121, 36-38), and serial monitoring with an electrocardiogram is the necessary to check for covert dysrhythmia. Hypogonadism and insulin resistance need monitoring in both diseases. Myotonia tends to be less marked and less troublesome in DM2, but in specific circumstances antimyotonia therapy is helpful, especially if muscle stiffness is frequent and persistent or if pain is prominent (92). Cognitive difficulties also occur in DM2 as in DM1 but become manifest in adult life and appear to be associated with decreased cerebral blood flow to frontal and anterior temporal lobes (39, 93) and decreased brain volume (94, 95). The changes are less severe than in DM1. Their aetiology is unknown but may relate to the toxic effect of intranuclear accumulations of abnormally expanded RNA.

A palm based interactive tailored patient assessment, containing a selection of symptoms, problems and concerns, rating of this items from 1–4 and prioritization for support was tested in 145 lymphoma and leukemia patients in a single centre in Norway. The assessment output was immediately

delivered to treating physicians and nurses in the intervention group. The outcomes measured were the Inhibitors,research,lifescience,medical same assessments: Numbers of symptom problems and concerns addressed, change in symptom distress and need for support. In the intervention group there were more Ruxolitinib molecular weight symptoms addressed, less symptom distress measured and patient were less in need for symptom management support [48]. A second randomized controlled trial investigated the effect of the ESRA-C (electronic self-report assessment cancer) on in 660 cancer patients at two institutions. The output from the ESRA-C was displayed to the treatment team in the intervention group. The primary outcome was

the likelihood of discussion of symptoms and quality of life issues (SQLIs) between clinicians and Inhibitors,research,lifescience,medical patients and the secondary endpoints the visit duration and the perceived usefulness by clinicians. When the SQLIs were considered as problematic, they were more frequently discussed during the visit in the intervention group; the length of visit time was equal between the two groups. The clinicians perceived the output as useful [20]. Strengths The strength of our approach, is the defined Inhibitors,research,lifescience,medical clinical setting, chemotherapy in palliative intention, where Inhibitors,research,lifescience,medical disease related symptoms, treatment related toxicities and clinical benefit parameters guide treatment. In contrast to the previous studies which aimed at a general improvement of communication our study aims to improve symptom control due to more in depth symptom assessment and adaption of chemotherapy due to Inhibitors,research,lifescience,medical better monitoring of toxicity and clinical benefit parameters. A second strength is the multicenter setting which tests the intervention in a real life environment and differences

between centers can be further studied. The main focus on specific and generic patient reported outcomes (quality of life, and symptoms) reflects patient centered these care in the oncological setting. Limitations E-MOSAIC intervention may be effective on several levels (i.e., awareness of patient, awareness of physician, coping, symptom control, communication), this study tests the hypothesis to overall improve the quality of palliative cancer care, rather than focusing on specific outcomes only. Global single-item QoL indicators are similarly efficient as multi-item scales for overall treatment comparisons and changes over time because they reflect the summation of the individual meaning and importance of various factors [38]. The use of a single-item tool to appropriately obtain a measure of overall QoL was reported from a cooperative multicenter study setting [49]. Patient-rated QoL may be influenced by many factors.

40 Taken together, serotonergic hallucinogens and psychotomimetic NM..DA antagonists produce schizophrenia-like deficits in behavioral measures of sensory gating such as PPI, and do so by actions localized to different parts of the CSPT circuitry. Despite their different primary mechanisms and sites of action, however, a common denominator of the effects of these drug classes is that they alter the dynamics of the integrated Inhibitors,research,lifescience,medical CSPT circuitry such that normal information processing is

distorted by deficits in fundamental forms of sensorimotor gating. Serotonergic amphetamines; MDMA Psychological effects In contrast to serotonergic hallucinogens and NMDA antagonists, a typical recreational and nontoxic dose of MDMA (1.5-7 mg/kg PO) produces an affective state of enhanced mood, profound Inhibitors,research,lifescience,medical well-being, happiness, increased extroversion and sociability, slight derealization and depersonalization, little anxiety, and moderate thought disturbances, but no hallucinations in normal volunteers.95 Depersonalization phenomena are mild and, in contrast to hallucinogens (eg, psilocybin), not experienced as problematic or psychotic fusion, but experienced as a pleasurable state of loosened ego boundaries as measured by the APZ Selleckchem ROCK inhibitor questionnaire (Figure 2). Similar findings were reported with MDMA

and its congener MDE in healthy Inhibitors,research,lifescience,medical volunteers.96-100 Brain imaging studies To identify the functional neuroanatomy involved in the action of MDMA in humans, the effect of MDMA (1.7 mg/kg) versus placebo on regional cerebral blood flow (C.BF) was investigated in MDMA-naive human subjects using PET and Inhibitors,research,lifescience,medical [H2 15O]-PET.101 M.DMA moderately increased brain activity as indexed by CBF bilaterally in the ventromedial prefrontal cortex, the ventral anterior cingulate, the inferior temporal lobe, and the medial occipital cortex and in the cerebellum. Decreases in CBF were found bilaterally in the motor and somatosensory cortex, Inhibitors,research,lifescience,medical the superior temporal lobe, the dorsal cingulate cortex, the insula, and the

thalamus. Unilateral decreases were found in the left amygdala, and the right parahippocampus. This activation pattern and associated affective state, which was characterized by heightened mood, increased extroversion, slight derealization, Levetiracetam and intensification of vision, substantially differ from those seen in ketamine- and psilocybin-induced psychosis-like syndromes. The activation of prefrontal and related limbic/paralimbic structures in conjunction with deactivation of the amygdala may underlie the emotional effects of MDMA. This view is consistent with findings implicating the amygdala,102,103 orbitofrontal cortex,103 ventral anterior cingulate cortex,103,104 prefrontal cortex, temporal lobe, and thalamus104 in the regulation of mood and emotion. In this network, the amygdala appears to play a pivotal role in the mediation of both positive and negative emotions.

Each volume consisted of 36 slices acquired parallel to the AC-PC plane (sequential acquisition; 3.5 mm thick with a 0.5 mm gap;

260 × 260 mm in-plane resolution, 64 × 64 matrix). The first three volumes were discarded to allow for magnetization equilibrium. A T1-weighted FSPGR structural image (TR = 7.7 msec, TE = 3.0 msec, flip angle 12°) was acquired for anatomical comparison. Cushions were placed around the participants’ head to minimize movement and earplugs and headphones were used to minimize noise. Behavioral analysis Effect of motivation on decision-making behavior Inhibitors,research,lifescience,medical Discrimination (d′) and response bias (c) were calculated using signal detection theory (Macmillan and Creelman 2009). Discrimination Inhibitors,research,lifescience,medical Alectinib chemical structure measures one’s ability to identify a target stimulus from a nontarget stimulus and is calculated using the inverse z-transformed hit rate (HR) and false-positive rate (FPR): A d′ score of 0 indicates an inability to discriminate between stimuli. The better an individual’s discrimination, the larger the d′ score.

Response bias is calculated as: Inhibitors,research,lifescience,medical and measures a participant’s willingness to say the target stimulus is present. A response bias equal to 0 indicates that a participant is equally likely to say a target or nontarget stimulus is present. A larger positive score indicates that the participant is less likely to say the target stimulus is present (conservative bias), while a large negative score indicates an increased willingness to say the target stimulus is present Inhibitors,research,lifescience,medical (liberal bias). Given the equal proportion of target and nontarget trials and the neutral Inhibitors,research,lifescience,medical payoff matrix in this study, the mathematically optimal response bias is neutral (c = 0). Two one-way, repeated-measures ANOVAs were used to test the effect of motivation on discrimination and response bias (IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY, USA: IBM Corp.). A two-way (4 × 2), repeated-measures ANOVA was used to examine the effect of motivation

and decision (Yes/No) on the natural log (ln) transformed response times (RT). nearly Greenhouse–Geisser corrections were applied when the assumption of nonsphericity was broken. Significant differences were identified at P < 0.05. Effect sizes were calculated using Pearson’s r. Values of r = 0.10, 0.30, and 0.50 reflect small, medium, and large effect sizes, respectively (Cohen 1988). Where there was a significant difference in response bias between levels of motivation, the change in response bias (Δc) was calculated as: The more negative Δc, the bigger the shift toward a more liberal response bias. The more positive Δc, the bigger the shift toward a more conservative response bias.

Cholinergic innervation is widespread throughout the brain innervating nearly every neural zone. Many cholinergic projections do not terminate at synapses, but rather nonsynaptically where they contribute to diffuse volume transmission (Dani and Bertrand 2007). This could be the case for most hippocampal and cortical projections

(Descarries et al. 1997), and would be similar to the action of other neurotransmitters including serotonin, dopamine, and noradrenaline (Vizi et al. 2010). Inhibitors,research,lifescience,medical What differentiates cholinergic transmission from these other neurotransmitters is that movement of acetylcholine (ACh) is via diffusion that is limited by acetylcholinesterase hydrolysis and not a reuptake pump (Dani and Bertrand 2007). Differently located nAChRs appear to exert different effects. Unlike in the periphery, where nAChR activation underpins fast neurotransmission at neuromuscular junctions, the role of fast transmission appears limited centrally although Inhibitors,research,lifescience,medical recent results suggest a possible role in hippocampal pyramidal neurons (Grybko et al. 2011). Many

studies have CP-868596 ic50 identified a role for nAChRs in modulating neurotransmitter concentrations, with activation of presynaptic nAChRs known to enhance release of neurotransmitters acetylcholine, dopamine, noradrenaline, serotonin, glutamate, Inhibitors,research,lifescience,medical and gamma-aminobutyric acid (GABA) (Dani and Bertrand 2007). This appears to be consequence of facilitating

increasing concentration of intracellular Ca2+ through augmenting calcium influx and altering activity of voltage-gated Ca2+ channels within the terminal. Alterations in multiple Inhibitors,research,lifescience,medical receptor regulated intracellular Ca2+ pathways are linked to mood and anxiety disorders (Plein and Berk 1999, 2001; Berk et al. 2001). Numerous investigations have explored how activation of nAChRs by nicotine can exert effects on mood and anxiety symptoms. Nicotine can lead Inhibitors,research,lifescience,medical to both anxiogenic and anxiolytic effects that appear to depend upon the animal strain, medroxyprogesterone dosing regimen, and experimental paradigm utilized. Exposure to nicotine in rat models leads to upregulation of nAChRs (Slotkin 2004) that is shortly followed by desensitization as exposure is continued. Activation of nAChRs, particularly the α4β2 and α7 subtypes, appears to enhance release of serotonin in several brain regions, including the dorsal raphe nucleus (Reuben and Clarke 2000; Ma et al. 2005). Interestingly, α4β2 receptor knockout mice demonstrate an increase in basal anxiety (Ross et al. 2000), suggesting a role for these receptors in anxiety regulation. These receptors also upregulate dopamine and noradrenergic neurons (Lichtensteiger et al. 1988), with these effects likely important in mediating the anxiolytic effects of nicotine (McGranahan et al. 2011).

In addition, age, the most significant risk factor for dementia, also plays a role in the extent of ADassociated neuropathology observed in the brain, irrespective of the presence or absence of dementia symptoms. Thus, if questions regarding the presence, absence, or extent of neuropathologic lesions or Ruxolitinib in vivo neurobiological Inhibitors,research,lifescience,medical changes are framed in the context of whether persons with MCI meet neuropathological criteria for AD, the results may lead to very different conclusions than if the questions are framed within the context of whether persons with MCI present with lesion densities or neurobiological changes that are different from those without cognitive impairments. In general,

Inhibitors,research,lifescience,medical the brains of persons with MCI do not meet neuropathological criteria for AD, but they nevertheless evidence pathological features that are qualitatively, but not quantitatively, AD-like (please see below). An illustrative example is a study of the association of neuritic plaques with cognitive compromise as defined by the CDR.35 Persons with no cognitive impairment were compared with those with different levels of impairment. Persons with CDRs of 0.5 (ie, MCI), had cortical neuritic plaque densities that were significantly higher than that of persons with intact Inhibitors,research,lifescience,medical cognition. Yet, the majority

of the studied sample with CDR scores of 0.5 and even those with CDR scores of 1 did not meet accepted neuropathological criteria lor AD.31,32,36 Similar results Inhibitors,research,lifescience,medical have been reported using different MCI classification schemes and different metrics of AD-associated lesion densities

(eg, ref 37). General neuropathology The majority of the studies of the neuropathology Inhibitors,research,lifescience,medical of MCI, especially degenerative/amnestic MCI,11,12 suggest that in most instances MCI is associated with a less fervent manifestation of the neuropathologies that are generally associated with dementia. Unselected MCI samples derived from memory clinic or general geriatric populations evidence a variety of neuropathologic lesions such as those associated with diffuse Lewy body disease, cerebrovascular disease, ischemic changes and hippocampal sclerosis, argtrophilic grain disease, Parkinson’s disease, and, of course, AD (eg, refs 37-40). Nearly invariably, the extent of these lesions is considerably 17-DMAG (Alvespimycin) HCl less than those observed in persons with frank dementia. In general, relative to persons with intact cognition, the frequency of AD-associated neuropathology in persons with MCI, especially those with amnestic MCI, is significantly greater than other neuropathologic lesions associated with dementia.40,41 Hallmark lesions of AD Alzheimer’s disease is characterized by extracellular neuritic plaques (NP) and intracellular neurofibrillary tangles (NFT).

At each center we used

several interventions: 1) Catheters could only be placed by those who were trained, certified, and had performed enough procedures to maintain competence. Often, simulation was used in initial training. 2) All catheters were placed using five barrier precautions, using standardized line kits. 3) Time outs and documentation were standardized. 4) Inhibitors,research,lifescience,medical Vigorous efforts by the leadership and clinical thought-leaders assured that these measures were performed every time, with every line. 5) Because we believed that catheters placed outside of our hospitals were not up to our standards, all such catheters were removed within hours of the patient’s arrival. As figure 2 shows, at BIDMC these measures reduced central line infection 9-fold, and the improvements have been maintained for years since the interventions began. UPMC and other hospitals in Pittsburgh participated in a joint effort to eliminate these infections; the results were reported in Morbidity and Mortality Weekly Reports under the title “Elimination of central line infections: Pittsburgh”. Inhibitors,research,lifescience,medical More recently, a collaborative Inhibitors,research,lifescience,medical effort across the state of Michigan has resulted in sharp reductions in central line infections state-wide.9,10 Figure 2 Central line

infection rate in ICUs (CLABSI) by quarter, plotted on the ordinate as infections per thousand ICU patient days. FY refers to fiscal year. VENTILATOR-ASSOCIATED PNEUMONIA Endotracheal tubes provide ready access for mouth flora to enter the lung, often resulting in pneumonia. A large body of evidence has shown that adoption of several measures, including elevation of the head of the bed to 30 degrees, Inhibitors,research,lifescience,medical daily awakening of sedated ventilator patients, and frequent assessment of ability to remove the endotracheal tube, reduces the rate of ventilator-associated pneumonia (VAP).11 At both UPMC and BIDMC Inhibitors,research,lifescience,medical the ventilator bundle was adopted and performed on every patient, every day. The rate of VAP fell 10-fold with adoption of the bundle and

has remained at this new lower level for the past 2 years. With the adoption of these and other quality Epigenetic animal study improvement measures, length Thalidomide of stay in the ICUs fell 20%, permitting the same number of ICU beds to care for 20% more patients. This obviated the need to build an additional ICU to care for increasing ICU volume. Moreover, mortality in the ICU population fell 12%, so that for every 40 patients cared for in the ICUs, one less patient died. Since we care for 6,000 ICU patients per year, this means we now avoid deaths in some 150 patients per year. REDUCING IN-HOSPITAL CARDIOPULMONARY ARRESTS Retrospective forensic chart studies of patients who have undergone cardiopulmonary arrests reveal that up to 80% of cardiopulmonary arrests are preceded by some indication of physiologic instability, ranging from high fever to high or low pulse, to high or low respiratory rate, to loss of mental status, to marked nursing concern (reviewed in 12,13).