Oscillations of Drops with Mobile Contact Lines on the International Space Station: Elucidation of Terrestrial Inertial Droplet Spreading.

We analyze shape oscillations of sessile water drops with fully mobile contact lines (CL) aboard the International Space Station. The unique microgravity environment enables the study of centimeter-sized droplets with associated inertial-capillary motions. Plane-normal substrate vibrations induce resonance behaviors quantified by frequency scans from which the natural frequencies and mode shapes are identified for nine different hydrophobic surfaces. Experimental observations agree well with, and validate, a recent spectral prediction of mobile CL sessile drop oscillations. The experimental findings help elucidate terrestrial droplet inertial spreading, a poorly understood phenomenon pervasive in many processes.

11ß-hydroxysteroid dehydrogenase type 1 has no effect on survival during experimental malaria but affects parasitemia in a parasite strain-specific manner.

Malaria is a global disease associated with considerable mortality and morbidity. An appropriately balanced immune response is crucial in determining the outcome of malarial infection. The glucocorticoid (GC) metabolising enzyme, 11ß-hydroxysteroid dehydrogenase-1 (11ß-HSD1) converts intrinsically inert GCs into active GCs. 11ß-HSD1 shapes endogenous GC action and is immunomodulatory. We investigated the role of 11ß-HSD1 in two mouse models of malaria. 11ß-HSD1 deficiency did not affect survival after malaria infection, but it increased disease severity and parasitemia in mice infected with Plasmodium chabaudi AS. In contrast, 11ß-HSD1 deficiency rather decreased parasitemia in mice infected with the reticulocyte-restricted parasite Plasmodium berghei NK65 1556Cl1. Malaria-induced antibody production and pathology were unaltered by 11ß-HSD1 deficiency though plasma levels of IL-4, IL-6 and TNF-α were slightly affected by 11ß-HSD1 deficiency, dependent on the infecting parasite. These data suggest that 11ß-HSD1 is not crucial for survival of experimental malaria, but alters its progression in a parasite strain-specific manner.

A double-blind, placebo-controlled randomized trial of creatine for the cancer anorexia/weight loss syndrome (N02C4): an Alliance trial.

BACKGROUND: Multiple pilot studies, including one in colorectal cancer patients, suggest that creatine, an amino acid derivative, augments muscle, improves strength, and thereby could palliate the cancer anorexia/weight loss syndrome. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled trial, incurable patients with this syndrome were assigned creatine (20 g/day load×5 days followed by 2 g/day orally) versus identical placebo. Patients were weighed once a week for 1 month and then monthly. Patients were also assessed over 1 month for appetite and quality of life (validated questionnaires), fist grip strength, body composition (bioelectrical impedance), and adverse events. The primary endpoint was 10% or greater weight gain from baseline during the first month. RESULTS: Within this combined cohort of 263 evaluable patients (134 received creatine and 129 placebo), only 3 gained ≥10% of their baseline weight by 1 month: two creatine-treated and the other placebo-exposed (P = 1.00). Questionnaire data on appetite, quality of life, and activities of daily living showed no statistically significant differences between groups. Similarly, no statistically significant differences between groups were observed for fist-grip strength or body composition. Rates and severity of adverse events were comparable between groups. Finally, a median survival of 230 and 239 days were observed in the creatine and placebo groups, respectively (P = 0.70). CONCLUSION: Creatine, as prescribed in this trial, had no effect on the cancer anorexia/weight loss syndrome.

Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance).

BACKGROUND: Carboplatin (C) and paclitaxel (P) are standard treatments for carcinoma of unknown primary (CUP). Everolimus, an mTOR inhibitor, exhibits activity in diverse cancer types. We did a phase II trial combining everolimus with CP for CUP. We also evaluated whether a gene expression profiling (GEP) test that predicts tissue of origin (TOO) could identify responsive patients. PATIENTS AND METHODS: A tumor biopsy was required for central confirmation of CUP and GEP. Patients with metastatic, untreated CUP received everolimus (30 mg weekly) with P (200 mg/m(2)) and C (area under the curve 6) every 3 weeks. The primary end point was response rate (RR), with 22% needed for success. The GEP test categorized patients into two groups: those having a TOO where CP is versus is not considered standard therapy. RESULTS: Of 45 assessable patients, the RR was 36% (95% confidence interval 22% to 51%), which met criteria for success. Grade ≥3 toxicities were predominantly hematologic (80%). Adequate tissue for GEP was available in 38 patients and predicted 10 different TOOs. Patients with a TOO where platinum/taxane is a standard (n = 19) tended to have higher RR (53% versus 26%) and significantly longer PFS (6.4 versus 3.5 months) and OS (17.8 versus 8.3 months, P = 0.005), compared with patients (n = 19) with a TOO where platinum/taxane is not standard. CONCLUSIONS: Everolimus combined with CP demonstrated promising antitumor activity and an acceptable side-effect profile. A tumor biomarker identifying TOO may be useful to select CUP patients for specific antitumor regimens. CLINICALTRIALSGOV: NCT00936702.

Effects of early amiodarone administration during and immediately after cardiopulmonary resuscitation in a swine model.

BACKGROUND: Aim of this experimental study was to compare haemodynamic effects and outcome with early administration of amiodarone and adrenaline vs. adrenaline alone in pigs with prolonged ventricular fibrillation (VF). METHODS: After 8 min of untreated VF arrest, bolus doses were administered of adrenaline (0.02 mg/kg) and either amiodarone (5 mg/kg) or saline (n = 8 per group) after randomisation. Cardiopulmonary resuscitation (CPR) was commenced immediately after drug administration, and defibrillation was attempted 2 min later. CPR was resumed for another 2 min after each defibrillation attempt, and the same dose of adrenaline was given every 4th minute during CPR. Haemodynamic monitoring and mechanical ventilation continued for 6 h after return of spontaneous circulation (ROSC), and the pigs were euthanised at 48 h. Researchers were blinded for drug groups throughout the study. RESULTS: There was no difference in rates of ROSC and 48-h survival with amiodarone vs. saline (5/8 vs. 7/8 and 0/8 vs. 3/8, respectively). Diastolic aortic pressure and coronary perfusion pressure were significantly lower with amiodarone during CPR and 1 min after ROSC (P < 0.05). The number of electric shocks required for terminating VF, time to ROSC and adrenaline dose were significantly higher with amiodarone (P < 0.01). The incidence of post-resuscitation tachyarrhythmias tended to be higher in the saline group (P = 0.081). CONCLUSION: Early administration of amiodarone did not improve ROSC or 48-h survival rates, and was associated with worse haemodynamics in this swine model of cardiac arrest.

Quantification of microbial risks to human health caused by waterborne viruses and bacteria in an urban slum.

AIMS: To determine the magnitude of microbial risks from waterborne viruses and bacteria in Bwaise III in Kampala (Uganda), a typical slum in Sub-Saharan Africa. METHODS AND RESULTS: A quantitative microbial risk assessment (QMRA) was carried out to determine the magnitude of microbial risks from waterborne pathogens through various exposure pathways in Bwaise III in Kampala (Uganda). This was based on the concentration of Escherichia coli O157:H7, Salmonella spp., rotavirus (RV) and human adenoviruses F and G (HAdV) in spring water, tap water, surface water, grey water and contaminated soil samples. The total disease burden was 680 disability-adjusted life years (DALYs) per 1000 persons per year. The highest disease burden contribution was caused by exposure to surface water open drainage channels (39%) followed by exposure to grey water in tertiary drains (24%), storage containers (22%), unprotected springs (8%), contaminated soil (7%) and tap water (0.02%). The highest percentage of the mean estimated infections was caused by E. coli O157:H7 (41%) followed by HAdV (32%), RV (20%) and Salmonella spp. (7%). In addition, the highest infection risk was 1 caused by HAdV in surface water at the slum outlet, while the lowest infection risk was 2.71 × 10(-6) caused by E. coli O157:H7 in tap water. CONCLUSIONS: The results show that the slum environment is polluted, and the disease burden from each of the exposure routes in Bwaise III slum, with the exception of tap water, was much higher than the WHO reference level of tolerable risk of 1 × 10(-6) DALYs per person per year. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this study provide guidance to governments, local authorities and nongovernment organizations in making decisions on measures to reduce infection risk and the disease burden by 10(2) to 10(5) depending on the source of exposure to achieve the desired health impacts. The infection risk may be reduced by sustainable management of human excreta and grey water, coupled with risk communication during hygiene awareness campaigns at household and community level. The data also provide a basis to make strategic investments to improve sanitary conditions in urban slums.

N0539 phase II trial of fulvestrant and bevacizumab in patients with metastatic breast cancer previously treated with an aromatase inhibitor: a North Central Cancer Treatment Group (now Alliance) trial.

BACKGROUND: Based on preclinical studies, the vascular endothelial pathway is an important mechanism for estrogen receptor resistance. We conducted a phase II study of fulvestrant and bevacizumab in patients with aromatase inhibitor pretreated metastatic breast cancer. PATIENTS AND METHODS: A single-stage phase II study was conducted with these objectives: 6-month progression-free survival (PFS), tumor response, toxic effect, and overall survival. Regimen: 250 mg fulvestrant days 1 and 15 (cycle 1) then day 1 (cycle 2 and beyond) and 10 mg/kg bevacizumab days 1 and 15 of each 4-week cycle. RESULTS: At interim analysis, 20 eligible patients initiated treatment, 11 were progression free and on treatment at 3 months, not meeting the protocol-specified efficacy requirements (at least 12 of 20). Accrual remained open during interim analysis with 36 patients enrolling before final study closure. Among the 33 eligible patients, the median PFS was 6.2 months [95% confidence interval (CI) 3.6-10.1 months]. Of the 18 with measurable disease, 4 (22%) patients (95% CI 6% to 48%) had a confirmed tumor response (1 complete, 3 partial). The most common grade 3/4 adverse events were hypertension 3 (9%) and headache 3 (9%). CONCLUSIONS: The fulvestrant/bevacizumab combination is safe and tolerable; however, it did not meet its statistical end point.

Minimum alveolar concentration (MAC) for sevoflurane and xenon at normothermia and hypothermia in newborn pigs.

BACKGROUND: Neuroprotection from therapeutic hypothermia increases when combined with the anaesthetic gas xenon in animal studies. A clinical feasibility study of the combined treatment has been successfully undertaken in asphyxiated human term newborns. It is unknown whether xenon alone would be sufficient for sedation during hypothermia eliminating or reducing the need for other sedative or analgesic infusions in ventilated sick infants. Minimum alveolar concentration (MAC) of xenon is unknown in any neonatal species. METHODS: Eight newborn pigs were anaesthetised with sevoflurane alone and then sevoflurane plus xenon at two temperatures. Pigs were randomised to start at either 38.5°C or 33.5°C. MAC for sevoflurane was determined using the claw clamp technique at the preset body temperature. For xenon MAC determination, a background of 0.5 MAC sevoflurane was used, and 60% xenon added to the gas mixture. The relationship between sevoflurane and xenon MAC is assumed to be additive. Xenon concentrations were changed in 5% steps until a positive clamp reaction was noted. Pigs' temperature was changed to the second target, and two MAC determinations for sevoflurane and 0.5 MAC sevoflurane plus xenon were repeated. RESULTS: MAC for sevoflurane was 4.1% [95% confidence interval (CI): 3.65-4.50] at 38.5°C and 3.05% (CI: 2.63-3.48) at 33.5°C, a significant reduction. MAC for xenon was 120% at 38.5°C and 116% at 33.5°C, not different. CONCLUSION: In newborn swine sevoflurane, MAC was temperature dependent, while xenon MAC was independent of temperature. There was large individual variability in xenon MAC, from 60% to 120%.

Prediction of countershock success in patients using the autoregressive spectral estimation.

OBJECTIVES: Ventricular fibrillation (VF) is a life-threatening cardiac arrhythmia and within of minutes of its occurrence, optimal timing of countershock therapy is highly warranted to improve the chance of survival. This study was designed to investigate whether the autoregressive (AR) estimation technique was capable to reliably predict countershock success in VF cardiac arrest patients. METHODS: ECG data of 1077 countershocks applied to 197 cardiac arrest patients with out-of-hospital and in-hospital cardiac arrest between March 2002 and July 2004 were retrospectively analyzed. The ECG from the 2.5 s interval of the precountershock VF ECG was used for computing the AR based features Spectral Pole Power (SPP) and Spectral Pole Power with Dominant Frequency weighing (SPPDF) and Centroid Frequency (CF) and Amplitude Spectrum Area (AMSA) based on Fast Fourier Transformation (FFT). RESULTS: With ROC AUC values up to 84.1% and diagnostic odds ratio up to 19.12 AR based features SPP and SPPDF have better prediction power than the FFT based features CF (80.5%; 6.56) and AMSA (82.1%; 8.79). CONCLUSIONS: AR estimation based features are promising alternatives to FFT based features for countershock outcome when analyzing human data.

Ajuga remota Benth.: from ethnopharmacology to phytomedical perspective in the treatment of malaria.

Treatment and control of malaria have become more difficult with the spread of drug-resistant parasites and insecticide-resistant mosquito vectors. In the search for new antimalarial drugs, ethnopharmacological sources should merit more attention. Establishing the safety of traditional herbal medicines, along with identifying their active principles, are essential steps in the production of a properly standardized and accessible herbal medicine. Phytochemical characterization could also serve as a base for the development of new chemical compounds. The genus of Ajuga belongs to the family Lamiaceae and contains at least 301 species. Many of these plants have been used in traditional medicine. Ajuga remota in particular is traditionally used as a herbal remedy for fever and infections, and is prescribed for malaria by 66% of the Kenyan herbalists. A large number of compounds have already been isolated from A. remota, including ergosterol-5,8-endoperoxide (6), ajugarin-I (1), 8-O-acetylharpagide (5) and several phytoecdysteroids. In vitro pharmacological studies have been conducted on constituents of A. remota of which some of them displayed a concentration-dependent inhibition of chloroquine-sensitive and -resistant Plasmodium falciparum and Mycobacterium tuberculosis. Inhibition of parasitaemia was demonstrated in mouse models with P. berghei, supporting the traditional use of the plant against malaria. In this state-of-the-art review, A. remota as a possible therapeutic tool for malaria is discussed.

Finite-amplitude dynamics of coupled cylindrical menisci.

The cylindrical meniscus is a liquid/gas interface of circular-cap cross-section constrained along its axis and bounded by end-planes. The inviscid motions of coupled cylindrical menisci are studied here. Motions result from the competition between inertia and surface tension forces. Restriction to shapes that are of circular-cap cross-section leads to an ordinary differential equation (ode) model, with the advantage that finite-amplitude stability can be examined. The second-order nonlinear ode model has a Hamiltonian structure, showing dynamical behavior like the Duffing-oscillator. The energy landscape has either a single- or double-welled potential depending on the extent of volume overfill. Total liquid volume is a bifurcation parameter, as in the corresponding problem for coupled spherical-cap droplets. Unlike the spherical-cap problem, however, axial disturbances can also destabilize, depending on overfill. For large volumes, previously known axial stability results are applied to find the limit at which axial symmetry is lost and comparison is made to the Plateau-Rayleigh limit.

Malaria: host-pathogen interactions, immunopathological complications and therapy.

Malaria is a global tropical disease causing more than 1 million deaths and 300 million clinical cases every year. It is caused by parasites from the genus Plasmodium and is transmitted by Anopheles mosquitoes. Approximately 3 billion people live in malaria-endemic regions and a majority of them are infected. In this review, we discuss the life cycle of the parasite, the complex interactions with the human host and the ensuing immune reactions and complications. The immune system plays a dual role in malaria, by providing life-saving immunity against the parasite, but also by causing often lethal complications in a number of patients. Cytokines, chemokines and proteases are key players in the immunopathological complications, and we propose immunomodulation with dexamethasone as a promising strategy for the therapy of malaria-associated acute respiratory distress syndrome.

Neutrophil responses to injury or inflammation impair peripheral gustatory function.

The adult peripheral taste system is capable of extensive functional plasticity after injury. Sectioning the chorda tympani (CT), a primary sensory afferent nerve, elicits transient changes in the uninjured, contralateral population of taste receptor cells. Remarkably, the deficits are specific to the sodium transduction pathway. Normal function is quickly restored in the intact nerve, in parallel with an influx of macrophages to both the denervated and uninjured sides of the tongue. However, changing the dietary environment by restricting sodium blocks the macrophage response and prolongs functional alterations. Since the functional deficits occur before macrophages are present in the peripheral taste system, we hypothesized that neutrophils play a role in modulating neural responses in the intact CT. First, the dynamics of the neutrophil response to nerve injury were analyzed in control-fed and sodium-deficient rats. Nerve sectioning briefly increased the number of neutrophils on both the denervated and uninjured sides of the tongue. The low-sodium diet amplified and extended the bilateral neutrophil response to injury, in parallel with the persistent changes in sodium taste function. To test the impact of neutrophils on taste function, we depleted these cells prior to nerve sectioning and recorded neural responses from the intact CT. This treatment restored normal sodium responses in the uninjured nerve. Moreover, recruiting neutrophils to the tongue induced deficits in sodium taste function in both CT nerves. Neutrophils play a critical role in ongoing inflammatory responses in the oral cavity, and may induce changes in taste perception. We also suggest that balanced neutrophil and macrophage responses enable normal neural responses after neural injury.

Inhibition of enzymatic degradation of adhesive-dentin interfaces.

Adhesive procedures activate dentin-associated matrix metalloproteinases (MMPs), and so iatrogenically initiate bond degradation. We hypothesized that adding MMP inhibitors to adhesive primers may prevent this endogenous enzymatic degradation, thereby improving bond durability. A non-specific MMP inhibitor (chlorhexidine) and a MMP-2/9-specific inhibitor (SB-3CT) were admixed to the primers of an etch & rinse and a self-etch adhesive, both considered as gold-standard adhesives within their respective categories. For dentin powder exposed to the adhesives under clinical application conditions, gelatin zymography revealed the release of MMP-2 (not of MMP-9) by the etch & rinse adhesive, while no release of enzymes could be detected for the mild self-etch adhesive, most likely because of its limited dentin demineralization effect. The built-in MMP inhibitors appeared effective in reducing bond degradation only for the etch & rinse adhesive, and not for the self-etch adhesive. Water sorption of adhesive interfaces most likely remains the principal mechanism of bond degradation, while endogenous enzymes appear to contribute to bond degradation of only etch & rinse adhesives.

Standard basic life support vs. continuous chest compressions only in out-of-hospital cardiac arrest.

BACKGROUND: The importance of ventilations after cardiac arrest has been much debated recently and eliminating mouth-to-mouth ventilations for bystanders has been suggested as a means to increase bystander cardiopulmonary resuscitation (CPR). Standard basic life support (S-BLS) is not documented to be superior to continuous chest compressions (CCC). METHODS: Retrospective, observational study of all non-traumatic cardiac arrest patients older than 18 years between May 2003 and December 2006 treated by the community-run emergency medical service (EMS) in Oslo. Outcome for patients receiving S-BLS was compared with patients receiving CCC. All Utstein characteristics were registered for both patient groups as well as for patients not receiving any bystander CPR by reviewing Ambulance run sheets, Utstein forms and hospital records. Method of bystander CPR as well as dispatcher instruction was registered by first-arriving ambulance personnel. RESULTS: Six-hundred ninety-five out of 809 cardiac arrests in our EMS were included in this study. Two-hundred eighty-one (40%) received S-CPR and 145 (21%) received CCC. There were no differences in outcome between the two patient groups, with 35 (13%) discharged with a favourable outcome for the S-BLS group and 15 (10%) in the CCC group (P=0.859). Similarly, there was no difference in survival subgroup analysis of patients presenting with initial ventricular fibrillation/ventricular tachycardia after witnessed arrest, with 32 (29%) and 10 (28%) patients discharged from hospital in the S-BLS and CCC groups, respectively (P=0.972). CONCLUSIONS: Patients receiving CCC from bystanders did not have a worse outcome than patients receiving standard CPR, even with a tendency towards a higher distribution of known negative predictive features.

Matrix metalloproteinase-9/gelatinase B is a putative therapeutic target of chronic obstructive pulmonary disease and multiple sclerosis.

Matrix metalloproteinases (MMPs) are a large family of proteolytic enzymes involved in an array of physiological and pathological processes from development, morphogenesis, reproduction, wound healing, and aging to inflammation, angiogenesis, neurological disorders, and cancer cell invasion and metastasis. The imbalance between MMP activity and the inhibitory action of tissue inhibitors of metalloproteinases (TIMPs) are implicated in multiple diseases. Secreted in the body in a latent form, upon activation MMP-9 (gelatinase B) acts on many inflammatory substrates, and thus is suspected of contributing to the progression of cardiovascular disease, rheumatoid arthritis, and the subjects of this review, chronic obstructive pulmonary disease (COPD) and multiple sclerosis (MS). COPD is the fourth most common cause of death in the United States. In COPD, increased expression of MMP-9 by inflammatory cells e.g. neutrophils and macrophages is correlated with a variety of processes that cause lung damage. MMP-9 is also important in cytokine and protease modulation; it degrades the serine protease inhibitor alpha(1)-antitrypsin, which thus may lead to lung destruction. MS affects approximately 400,000 Americans and over a million people worldwide. Upregulation of MMP-9 increases the permeability of the blood brain barrier (BBB), facilitates the infiltration of leukocytes into the central nervous system, and causes myelin sheath degradation and neuronal damage. Early stage clinical trials have shown promising results when MMP-9 is inhibited in MS. These observations lead to the hypothesis that MMP-9 is a potential drug target for both COPD and MS and further development of highly potent and specific MMP-9 inhibitors is warranted.

Detection of carbon dioxide in expired air after oesophageal intubation; the role of bystander mouth-to-mouth ventilation.

BACKGROUND: The identification of a correctly placed tube during anaesthesia routinely depends on the detection of carbon dioxide (CO2) in the expired air. RESULTS: We describe a previously unreported cause of false-positive prediction in two patients with high initial values of CO2 in expired air after oesophageal intubation. Both patients had received bystander cardiopulmonary resuscitation with mouth-to-mouth ventilation, and the CO2 from the rescuers' expired air was trapped and subsequently detected after oesophageal intubation.

Misplaced and dislodged endotracheal tubes may be detected by the defibrillator during cardiopulmonary resuscitation.

We present two cases of unrecognized endotracheal tube misplacements in out-of-hospital cardiopulmonary resuscitation recognized by the analysis of transthoracic impedance. In Case 1, ventilation-induced changes in transthoracic impedance disappeared after an intubation attempt corresponding to oesophageal intubation. This was clinically recognized after several minutes, the endotracheal tube was repositioned and alterations in transthoracic impedance resumed. In Case 2, the initial ventilation-induced signal change following endotracheal intubation weakened after a few minutes. At that time, the defibrillator gave vocal and visual feedback to the rescuers on ventilatory inactivity, a pharyngeal air leak was discovered simultaneously and the tube was found to be dislodged. Continuous monitoring of transthoracic impedance provided by the defibrillator during cardiopulmonary resuscitation may contribute to the early detection of an initially misplaced or later dislodged endotracheal tube.

Compression force-depth relationship during out-of-hospital cardiopulmonary resuscitation.

BACKGROUND: Recent clinical studies reporting the high frequency of inadequate chest compression depth (<38 mm) during CPR, have prompted the question if adult human chest characteristics render it difficult to attain the recommended compression depth in certain patients. MATERIAL AND METHODS: Using a specially designed monitor/defibrillator equipped with a sternal pad fitted with an accelerometer and a pressure sensor, compression force and depth was measured during CPR in 91 adult out-of-hospital cardiac arrest patients. RESULTS: There was a strong non-linear relationship between the force of compression and depth achieved. Mean applied force for all patients was 30.3+/-8.2 kg and mean absolute compression depth 42+/-8 mm. For 87 of 91 patients 38 mm compression depth was obtained with less than 50 kg. Stiffer chests were compressed more forcefully than softer chests (p<0.001), but softer chests were compressed more deeply than stiffer chests (p=0.001). The force needed to reach 38 mm compression depth (F38) and mean compression force were higher for males than for females: 29.8+/-14.5 kg versus 22.5+/-10.2 kg (p<0.02), and 32.0+/-8.3 kg versus 27.0+/-7.0 kg (p<0.01), respectively. There was no significant variation in F38 or compression depth with age, but a significant 1.5 kg mean decrease in applied force for each 10 years increase in age (p<0.05). Chest stiffness decreased significantly (p<0.0001) with an increasing number of compressions performed. Average residual force during decompression was 1.7+/-1.0 kg, corresponding to an average residual depth of 3+/-2 mm. CONCLUSION: In most out-of-hospital cardiac arrest victims adequate chest compression depth can be achieved by a force<50 kg, indicating that an average sized and fit rescuer should be able to perform effective CPR in most adult patients.