One of the

major simplifications of CG models is the repr

One of the

major simplifications of CG models is the representation of the solvent, which is either implicit or modeled explicitly as a van der Waals particle. The effect of polarization, and thus a proper screening of interactions ON-01910 datasheet depending on the local environment, is absent. Given the important role of water as a ubiquitous solvent in biological systems, its treatment is crucial to the properties derived from simulation studies. Here, we parameterize a polarizable coarse-grained water model to be used in combination with the CG MARTINI force field. Using a three-bead model to represent four water molecules, we show that the orientational polarizability of real water can be effectively accounted

for. This has the consequence that the dielectric screening of bulk water is reproduced. At the same time, we parameterized our new water model such that bulk water density and oil/water partitioning data remain at the same level of accuracy PF-04929113 as for the standard MARTINI force field. We apply the new model to two cases for which current CG force fields are inadequate. First, we address the transport of ions across a lipid membrane. The computed potential of mean force shows that the ions now naturally feel the change in dielectric medium when moving from the high dielectric aqueous phase toward the low dielectric membrane interior. In the second application we consider the electroporation process of both an oil slab and a lipid bilayer. The electrostatic field drives the formation of water filled pores in both cases, following a similar mechanism as seen with atomistically detailed models.”
“Using electric field-induced second harmonic generation (EFISHG) measurements, we directly probed a time-varying space charge field responsible for carrier injection followed by radiative recombination (electroluminescence; EL). Experiments

using tetracene as the active layer of a top-contact field-effect transistor with application of a pulsed voltage showed that a JQ-EZ-05 chemical structure space charge field remained around the source electrode-caused by injected holes, but not by electrons. Observing the time-varying EFISHG intensity at the electrodes clearly showed that the space charge field formed in the vicinity of the electrodes made a dominant contribution to the opposite-polarity carrier injection, directly leading to EL around the electrodes by carrier recombination. We concluded that EFISHG measurement is useful for probing carrier behavior in luminescent materials, by eliminating two-photon excited photoluminescence from the material induced using an incident laser. (C) 2011 American Institute of Physics. [doi:10.1063/1.3554835]“
“Background: Switching warfarin for heparin has been a practice for managing periprocedural anticoagulation in high-risk patients undergoing device-related procedures.

From the global decays of the Nd3+ F-4(3/2) level in single and c

From the global decays of the Nd3+ F-4(3/2) level in single and codoped samples,

the transfer efficiencies were estimated; they increase with Yb3+ content reaching similar to 93% for 1 at. learn more % Nd, 5 at. % Yb: YAG sample. The mechanisms and parameters of the Nd. Yb energy transfer were inferred from the Nd3+ decays in the codoped samples, after the separation of the self-quenching inside the donors (Nd3+) from the transfer to acceptors (Yb3+). It was proved that the Nd. Yb energy is resonant and dominated by dipole-dipole interactions. Due to the large transfer efficiencies, (Nd,Yb):YAG ceramic could be a promising material for Yb3+ emission under pumping in strong Nd3+ absorption lines. (c) 2010 American Institute of Physics. [doi: 10.1063/1.3525269]“
“In the oral cavity, chronic inflammation has been observed at various stages of oral squamous cell carcinomas (OSCC). Such inflammation could result from persistent mucosal or epithelial cell colonization by microorganisms. There is increasing evidence of the involvement of oral bacteria in inflammation, warranting NVP-LDE225 further studies on the association of bacteria with the progression of OSCC. The objective of this study was to evaluate the diversity and relative abundance of bacteria in the saliva of subjects with OSCC. Using 454 parallel DNA

sequencing, similar to 58 000 PCR amplicons that span the V4-V5 hypervariable region of rRNAs from five subjects were sequenced. Members of eight phyla (divisions) of bacteria were detected. The majority of classified

sequences belonged to the phyla Firmicutes (45%) and Bacteroidetes (25%). Further, 52 different genera containing approximately 860 (16.51%) Microbiology inhibitor known species were identified and 1077 (67%) sequences belonging to various uncultured bacteria or unclassified groups. The species diversity estimates obtained with abundance-based coverage estimators and Chao1 were greater than published analyses of other microbial profiles from the oral cavity. Fifteen unique phylotypes were present in all three OSCC subjects.”
“We employ electroless etching to disperse silicon on insulator (SOI) wafers in ionic silver HF into wirelike silicon nanostructures. The procedure allows detachment of the nanowires at the oxide interface and enables easy recovery of dispersions for subsequent controlled delivery. Nanowires 10 mu m long and 50-100 nm thick are demonstrated using an SOI substrate of 10 mu m device thickness. Direct material analysis shows no silver contamination after a wet-etch silver clean. Anodization treatment of the wires was conducted. Our measurements and analysis show that the wires are not amenable to anodization resulting from the fact that the nanowire radius is less than the thickness of depletion layer.

New ionomers are currently being sought to replace the ionomers,

New ionomers are currently being sought to replace the ionomers, which contain fluorine and are harmful to environment and Elafibranor expensive. A new and promising ionomer is a sulfonated ethylene/styrene copolymer. A nearby alternating copolymer with styrene content of 47 mol % was polymerized with metallocene/MAO catalyst. Membranes were prepared by hot-pressing copolymer films with a glassfiber tissue. Phenyl

rings in the copolymers were sulfonated with chlorosulfonic acid as a sulfonating agent. As the alternating structure of the copolymer, sulfonic groups were evenly distributed along the membranes. The membranes were characterized by determining water uptake, ion exchange capacity, proton conductivity, and mechanical properties. The studies revealed that the sulfonated copolymers have promising properties for proton-conducting applications. All membranes had good ion exchange capacity, similar to 3.5 meq/g, and proton conductivity, over 50 mS/cm. Due to the high water uptake of the sulfonated copolymer, mechanical properties of the membranes were improved by using the glassfiber tissue

as reinforcement. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012″
“Alcohol use, abuse, and dependence have the potential learn more to result in alcoholic cardiomyopathy (ACM). This distinct form of congestive heart failure (CHF) is responsible for 21-36% of all cases of nonischemic dilated cardiomyopathy in Western society. Without complete abstinence, the 4-year mortality for ACM approaches 50%. Therefore, accurate and detailed assessment of alcohol GDC0068 use in congestive heart failure is essential. The prevalence

of problematic alcohol use is unrecognized by many clinicians. Clinical assessment of alcohol intake is often reduced to a simple question such as, “”Do you drink?”" Denial and minimization are hallmarks of alcohol abuse, with many individuals underreporting their use of alcohol. Clinicians can overcome these hurdles by implementing practical history taking measures to improve the accuracy of self-reported alcohol use. The data regarding the dangers of ongoing alcohol use in individuals with ACM make attempts to engage individuals in treatment to support abstinence essential. Suggestions for detailed and accurate assessment are discussed.”
“Numb chin syndrome (NCS), also known as mental nerve neuropathy, is characterized by facial and oral numbness restricted to the distribution of the mental nerve. Although not a common neuropathy, the clinical importance of this syndrome is its frequent association with malignancies, particularly breast cancer and lymphoma. In this paper, we present a rare case of Burkitt cell acute lymphocytic leukemia initially presenting with bilateral NCS. In this case, no abnormalities were detected on initial blood tests and radiologic investigations except for partial loss of lamina dura around mandibular teeth. Furthermore, we found no evidence of any other signs of central nervous system involvement apart from NCS.

5 x 10(12) to 3 x 10(13)/cm(2), while no noticeable shift is obse

5 x 10(12) to 3 x 10(13)/cm(2), while no noticeable shift is observed in that for the higher probing energy. Assuming the carriers rapidly thermalize after excitation, this indicates that the optical phonon emission time decreases from about 50 to about 20 fs and the energy relaxation TPX-0005 rate increases from 4 to 10 meV/fs. The observed density dependence is inconsistent with the phonon bottleneck effect. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3573674]“
“Purpose: To estimate the biological doses for two severely exposed subjects (A and B) in a radiation accident in Shandong Jining, China

in 2004.

Materials and methods: Conventional chromosome aberration analysis and cytokinesis-block micronuclei (CBMN) assay were performed in peripheral blood and bone marrow samples on two subjects after the accident. A new dose-effect curve and the nuclear division index (NDI) obtained from in vitro irradiation experiments using high dose of (60)Co gamma-rays were used to estimate the exposed doses.

Results: No metaphases or binucleated cells were observed in the peripheral blood cultures from either of the subjects. However, metaphases and binucleated cells were obtained from both subjects after bone marrow cultures.

Both dicentric/ring LY2603618 datasheet and micronuclei yields were very high. The dose estimated for A and B were 20.0 Gy and 8.8 Gy, respectively, by dicentric/ring scoring, similar to the data by combination of the CBMN and NDI (CBMN+NDI) assay. The estimated doses by the two methods were in accordance with the clinical symptoms.

Conclusion: The new curve, together with the CBMN+NDI assay, are reliable for estimating higher selleck doses of irradiation. In future radiation accidents, the accuracy and significance of these methods can be further tested.”
“Heart failure is a leading cause of morbidity and mortality worldwide. The current strategies for treatment are limited, and new therapeutic approaches are needed. Experimental studies and clinical trials suggest that stem cell

transplantation may improve cardiac function and prevent cardiac remodeling of the injured heart. Although the results of the studies were exciting, many problems remain to be resolved such as the best method of delivering the targeted cells. Direct injection into the myocardium and intracoronary artery infusion are the two most used methods of delivery in clinical settings. However, in a portion of patients with occluded coronary arteries and poor collaterals, transplanted cells may not reach the target ischemic lesion. To resolve this problem, we hypothesize that retrograde coronary venous delivery of stem cells may be a promising therapeutic strategy for the patients with occluded coronary arteries and poor collaterals.

Hence screw dislocations in AlN are established as highly promine

Hence screw dislocations in AlN are established as highly prominent conductive nanowires in semiconducting thin films and prospects for novel, highly functional nano-device materials through exploitation of screw TDs are attested. (C) 2011 American Institute of Physics. [doi:10.1063/1.3632985]“
“Background: Many of the foods abundant HM781-36B in vivo in the traditional Mediterranean diet, such as vegetables and fish, have been associated with slower cognitive

decline.

Objective: We investigated whether adherence to a Mediterranean dietary pattern or to the Healthy Eating Index-2005 (HEI-2005) is associated with cognitive change in older adults.

Design: This article is based on analyses of data from an ongoing longitudinal study in adults aged >= 65 y known as the Chicago Health and Aging Project (CHAP). CHAP participants (2280 blacks and 1510 whites) with >= 2 cognitive assessments were evaluated for adherence to 1) the Mediterranean dietary pattern (MedDiet; maximum score: 55) and 2) the HEI-2005 (maximum score: 100). For both scoring systems, higher scores connote greater adherence. Cognitive function was assessed at 3-y intervals on the basis of a composite measure of global cognition. Linear mixed models were used to examine

the association of dietary scores to change in cognitive function. Mean follow-up RG7112 time was 7.6 y.

Results: Mean (+/- SD) scores for participants were 28.2 +/- 0.1 for the MedDiet and 61.2 +/- 9.6 for the HEI-2005.

White participants had higher energy-adjusted MedDiet scores but lower HEI-2005 scores than did black participants. Higher MedDiet scores were associated with slower rates of cognitive decline (beta = +0.0014 per 1-point increase, SEE = 0.0004, P = 0.0004) after adjustment for age, sex, race, education, participation in cognitive activities, and energy. No such associations were observed for HEI-2005 scores.

Conclusion: The Mediterranean dietary pattern as captured by the MedDiet scoring system may reduce the rate of cognitive decline with older age. Am J Clin Nutr 2011;93:601-7.”
“Exposure of pregnant women and their unborn Navitoclax in vitro children to engineered nanoparticles (NPs) is not yet of major public concern. However, this may soon change in light of the ever-increasing production of NPs and the continuous appearance of novel NP-containing consumer products. However, NPs may not only pose risks to exposed individuals; they offer major potential for the development of novel therapeutic strategies to treat specifically either the mother or the developing foetus. Hence there is every reason to explore the transplacental transfer of engineered NPs in more detail, and to find answers to the vast number of open questions in this fascinating field of research.

As the temperature increases, an initial decrease followed by a s

As the temperature increases, an initial decrease followed by a subsequent increase of hysteresis

loss, P(h), and eddy current loss, P(e) is observed. Both P(h) and P(e) increase with increasing frequency. When f >= 300 kHz, a residual loss, P(r), appears. P(e) increases with increasing temperature and frequency. The temperature and frequency dependence of P(h) can be explained by irreversible domain wall movements, P(e) by the skin effect, and P(r) by domain wall resonance, respectively. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3581880]“
“Mechanical click here devices are sought to support insufficient or paralysed striated muscles including the failing heart. Nickel-titanium alloys (nitinol) present the following two properties: (i) super-elasticity, this website and (ii) the potential to assume different crystal structures depending on temperature

and/or stress. Starting from the martensite state nitinol is able to resume the austenite form (state of low potential energy and high entropy) even against an external resistance. This one-way shape change is deployed in self-expanding vascular stents. Heating induces the force generating transformation from martensite to the austenite state while cooling induces relaxation back to the martensite state. This two-way shape change oscillating between the two states may be used in cyclically contracting support devices of Alvocidib silicon-coated nitinol wires. Such a contractile

device sutured to the right atrium has been tested in vitro in a bench model and in vivo in sheep. The contraction properties of natural muscles, specifically of the myocardium, and the tight correlation with ATP production by oxidative phosphorylation in the mitochondria is briefly outlined. Force development by the nitinol device cannot be smoothly regulated as in natural muscle. Its mechanical impact is forced onto the natural muscle regardless of the actual condition with regard to metabolism and Ca(2+)-homeostasis. The development of artificial muscle on the basis of nitinol wires is still in its infancy. The nitinol artificial muscle will have to prove its viability in the various clinical settings.”
“The postictal state and its features were recognized by physicians from Babylonian times through to the advent of modern neurology in the late 19th century. Among varied descriptions and definitions lies one of the best known and still used eponyms in medicine, Todd’s paralysis. Despite a relative lack of biological insight, many key observations were made in an era mostly devoid of treatments for epilepsy. (C) 2010 Elsevier Inc. All rights reserved.”
“This research addresses the wavelength dependence of the fabrication of Ag nanostructures through photoinduced deposition using single crystal ferroelectric lithium niobate as a template.

In the evaluated study, the LPI GPR55 system in adipose tissue wa

In the evaluated study, the LPI GPR55 system in adipose tissue was examined. GPR55 is expressed in white adipose tissue and its expression is higher in visceral than in subcutaneous fat. GPR55 expression is higher in obese than in lean subjects, and in the obese group is greater in diabetic than in nondiabetic patients. In addition, plasma LPI concentration is increased in obese individuals. In vitro, LPI increases intracellular Ca2+ concentration and stimulates the expression of PPAR-gamma and genes involved in fatty

acid synthesis. In contrast to human adipocytes, LPI has no effect on triglyceride selleck products accumulation in rodent adipocytes and adipose tissue GPR55 expression is downregulated in both leptin-deficient mice and rats made obese by a high-fat diet, indicating that the role of GPR55 in adipose tissue is species specific.”
“Above-ground pipelires for in situ oil sands development are potentially significant vectors of habitat fragmentation for large mammals. We evaluated the use of elevated pipeline clearances (distance between the ground and the bottom of the pipeline) and pipeline crossing structures, I:he two primary methods of mitigating the barrier effect of above-ground pipelines on

large mammals, with a particular emphasis on moose (Alces alces), in northern Alberta, Canada. Winter snow tracking and remote cameras Blebbistatin mouse Tozasertib inhibitor were employed for one year to monitor large mammal interactions with a 5.5 km stretch of pipeline mitigated with five pipeline crossing structures and a 1.6 km control area of unmitigated pipeline. A minimum threshold pipeline clearance of 140 cm was critical in allowing adult moose to cross underneath the pipeline. Pipeline crossing structures facilitated movement across the pipeline and were used more than sections of elevated pipelines by all species. (C) 2008 Elsevier Ltd. All rights reserved.”
“After endosymbiosis, organelles lost most of their initial genome. Moreover, expression of the few remaining genes became tightly controlled by the nucleus through

trans-acting protein factors that are required for post-transcriptional expression (maturation/stability or translation) of a single (or a few) specific organelle target mRNA(s). Here, we characterize the nucleus-encoded TDA1 factor, which is specifically required for translation of the chloroplast atpA transcript that encodes subunit a of ATP synthase in Chlamydomonas reinhardtii. The sequence of TDA1 contains eight copies of a degenerate 38-residue motif, that we named octotrico peptide repeat (OPR), which has been previously described in a few other trans-acting factors targeted to the C. reinhardtii chloroplast. Interestingly, a proportion of the untranslated atpA transcripts are sequestered into high-density, non-polysomic, ribonucleoprotein complexes.

PCR amplification and direct sequencing of the WISP3 gene reveale

PCR amplification and direct sequencing of the WISP3 gene revealed a homozygous mutation at nucleotide 156 of the WISP3 gene, resulting in a Cys52-to-ter

substitution. This mutation has previously been reported in French, Italian, and Arab families. Interestingly, the C52X mutation was found to be associated with a c. 248G -> A (G83E) variation, suggesting the existence of a founder effect. By contrast, the presence of the same aberration in three different ethnic groups could imply that this particular site is prone to mutation. Basal fasting concentrations of growth hormone, insulin-like Proton Pump inhibitor growth factor-1, and insulin-like growth factor binding protein-3, as well as glucose and insulin

levels revealed no aberrations. In conclusion, consideration of this rare disease that causes significant morbidity with short stature, osteopenia www.selleckchem.com/PARP.html and arthritic complaints would prevent unnecessary examinations and treatment attempts. Testing for this specific mutation in suspected cases could provide a rapid and definitive diagnosis.”
“The mechanical and thermal characteristics and morphology of polyamide 6 (PA6)/isotactic polypropylene (iPP) blends (10/90 w/w) prepared with different processing procedures and incorporated with an aryl amide nucleating agent, a kind of beta-nucleating agent (beta-NA) for iPP, were investigated. The yield strength and flexural modulus of the blends decreased as beta-NA was introduced into the blends, whereas the impact strength and elongation at break improved. The crystalline structures of the blends closely depended on (1) the processing conditions and (2) competition between the beta-nucleating effect of beta-NA and the alpha-nucleating effect of PA6 for iPP. Scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction were adopted

to reveal the microstructures of the blends. At a low beta-NA content (< 0.1 wt %), the alpha-phase iPP dominated the blends, whereas the relative content of the beta-phase iPP increased remarkably when the CH5424802 in vivo beta-NA content was not less than 0.1 wt %. The processing conditions also showed profound influences on the supermolecular structures of iPP; this resulted in different mechanical properties of the blends. As for PA6, the crystallization behavior and crystalline structure did not exhibit obvious changes, but PA6 did play an important role in the epitaxial crystallization of iPP on PA6. (c) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 121: 554-562, 2011″
“Neurosyphilis is still a significant medical problem in developing countries and syphilitic ocular manifestations are often not diagnosed due to the lack of typical characteristics.

They may have an intrasheath subluxation of the peroneal tendons,

They may have an intrasheath subluxation of the peroneal tendons, which can be confirmed with use of a dynamic ultrasound. Surgical repair of tendon tears combined with a peroneal groove-deepening procedure with retinacular reefing is a reproducibly effective procedure for this condition.

LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence”
“Background. To evaluate the diagnostic and prognostic utility of monitoring the Epstein-Barr virus (EBV) load in learn more the cerebrospinal fluid (CSF) and peripheral blood for the patients with

EBV-associated central nervous system (CNS) diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT), 172 patients undergoing allo-HSCT were enrolled in the study.

Methods. The EBV DNA levels of blood were monitored regularly in recipients of transplants for 3 years post transplantation. The EBV DNA levels of CSF were monitored in patients with EBV-associated CNS diseases before the treatment and at different points following the treatment.

Results. Post-transplant EBV-associated diseases developed in 27 patients, including 12 patients with EBV-associated CNS diseases. The 3-year cumulative incidences of EBV-associated diseases and EBV-associated CNS diseases

were 19.5 PXD101 molecular weight similar to 3.5% and 8.6 similar to 2.4%, respectively. Patients with EBV-associated diseases showed higher loads of EBV DNA in their blood compared with patients with EBV DNA-emia. No difference was seen between the EBV DNA levels of blood in patients with CNS involvement and patients without CNS involvement. The EBV DNA loads of blood increased 3-14 days before the clinical manifestations of EBV-associated diseases emerged. The EBV DNA loads of CSF were higher than that of blood in patients with EBV-associated CNS diseases. In 12 patients

with EBV-associated CNS diseases, EBV DNA levels were declining in both blood and CSF with the control of diseases, and the EBV DNA loads of CSF decreased faster than that HIF inhibitor of blood in 5 patients who responded to treatment, and the EBV DNA levels of CSF increased in 5 patients who were unresponsive to treatment. On multivariate analysis, the use of anti-thymocyte globulin and intensified conditioning regimens were independent risk factors for EBV-associated diseases and EBV-associated CNS diseases.

Conclusions. EBV-associated CNS diseases are not rare after alloHSCT. The EBV DNA loads of CSF could act as an important indicator, but the EBV DNA loads of blood could not, for the diagnosis, prognosis, and therapeutic evaluation of EBV-associated CNS diseases.”
“BACKGROUND: The modified Ludloff proximal first metatarsal osteotomy is indicated for the surgical correction of moderate-to-severe hallux valgus deformity associated with metatarsus primus varus. We report the intermediate-term results of this procedure.

However, the PVA hydrogel prepared at 10,000 atm for 10 min exhib

However, the PVA hydrogel prepared at 10,000 atm for 10 min exhibited the slowest release rate of model drugs. Thus, we found that the release rates of the model drugs from the PVA hydrogels were controlled by the degree of crosslinking in the resulting gels, which was determined from the operation parameters of the ultrahigh-pressure treatment, such as the pressure, time, and concentration of the PVA solution. Therefore, an ultrahigh-pressure process is promising for drug-carrier development because of the nonharmful simple preparation process. (C) 2010 Wiley Periodicals,

Inc. J Appl Polym Sci 119: 2725-2729, 2011″
“Background: Infants less than 3 months of age are at highest risk of hospitalization and death from pertussis. Several studies have examined antibody responses to pertussis vaccines at birth but no previous study has evaluated 2 doses of monovalent acellular pertussis vaccine (aPV) before 2 months SBE-β-CD of age.

Methods: Seventy-six newborns were randomized at birth to 3 groups-aPV at birth and 1 month, aPV at birth, and control. All infants received hepatitis B vaccine (HBV) at birth followed at 2, 4, SRT2104 and 6 months by a combination vaccine including aPV, diphtheria, tetanus, Haemophilus influenzae type b (Hib), hepatitis B, polio antigens and 7 valent conjugate pneumococcal vaccine. IgG antibody responses to pertussis toxoid (PT), filamentous

hemagglutinin (FHA), and pertactin (PRN) were measured in maternal serum and in infants at 2, 4, buy LDK378 6, and 8 months of age. Antibody responses to hepatitis B, diphtheria, tetanus, and Hib were measured at 8 months only. A parental diary and active telephone follow-up occurred for 7 days after each vaccination.

Results: The aPV birth dose was well tolerated. By 2 months of age, 22 of 25 (88%) of 2 dose recipients had detectable IgG antibody to PT (IgG PT) compared with 9 of 21 (43%) who received a birth dose only and 3 of 20 (15%) of controls. Infants in the 2 dose group had a geometric mean concentration (GMC) of IgG PT of 16 ELISA units per mL (EU/mL), 95% CI: 11 to 25, significantly higher than birth dose only (5 EU/mL, 95% CI: 3-8) and controls

(3 EU/mL, 95% CI: 2-5). At 8 months of age, following 5, 4, and 3 doses of aP-containing vaccine, respectively, IgG PT had plateaued but IgG to FHA and PRN increased with successive doses. There was a trend to lower antibody responses for hepatitis B and Hib with higher numbers of Pa doses.

Conclusion: These data suggest that aPV at birth and 1 month induces significantly higher IgG antibody against pertussis antigens by 2 months of age without reducing subsequent pertussis antibody responses. Larger and more detailed studies of aPV from birth are needed to evaluate other antibody responses and the potential of this approach to reduce death and morbidity from Bordetella pertussis infection in the first 3 months of life.”
“BACKGROUND: Heart disease and stroke are leading causes of death in North America.