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This paper investigates the ability of subjective expectations about life expectancy to predict wealth holding patterns in later life. Based on panel data from the Asset and Health Dynamics among the Oldest Old, we estimate a structural life-cycle model with bequests. Each individual's subjective survival rates in the future are estimated with data on his belief of survival probabilities to a target age. This estimation is build upon a Bayesian updating method developed in Gan et al. (2005). We find that life-cycle model using subjective survival rates performs better than using life-table survival rates in predicting wealth holdings. This result suggests that subjective survival expectations play an important role in deciding consumption and savings. In addition, the estimation results show that most bequests are involuntary or accidental.

Previous studies have demonstrated that the otoacoustic emissions (OAEs) measured during behavioral tasks can have different magnitudes when subjects are attending selectively or not attending. The implication is that the cognitive and perceptual demands of a task can affect the first neural stage of auditory processing-the sensory receptors themselves. However, the directions of the reported attentional effects have been inconsistent, the magnitudes of the observed differences typically have been small, and comparisons across studies have been made difficult by significant procedural differences. In this study, a nonlinear version of the stimulus-frequency OAE (SFOAE), called the nSFOAE, was used to measure cochlear responses from human subjects while they simultaneously performed behavioral tasks requiring selective auditory attention (dichotic or diotic listening), selective visual attention, or relative inattention. Within subjects, the differences in nSFOAE magnitude between inattention and attention conditions were about 2-3 dB for both auditory and visual modalities, and the effect sizes for the differences typically were large for both nSFOAE magnitude and phase. These results reveal that the cochlear efferent reflex is differentially active during selective attention and inattention, for both auditory and visual tasks, although they do not reveal how attention is improved when efferent activity is greater.

The missing maxillary lateral incisor in adolescent patients presents an orthodontic challenge. Historically, there have been three treatment options to address this clinical problem: (1) canine substitution, (2) tooth auto-transplantation, and (3) dental restoration. Unfortunately, these methods are not without limitation. A novel treatment concept, originating in 2003 and utilizing orthodontic miniscrew implants, is presented along with the rationale, clinical technique and 8 years of follow-up., (© 2014 British Orthodontic Society.)

Both otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) are sexually dimorphic, and both are believed to be influenced by prenatal androgen exposure. OAEs and AEPs were collected from people affected by 1 of 3 categories of disorders of sex development (DSD) - (1) women with complete androgen insensitivity syndrome (CAIS); (2) women with congenital adrenal hyperplasia (CAH); and (3) individuals with 46,XY DSD including prenatal androgen exposure who developed a male gender despite initial rearing as females (men with DSD). Gender identity (GI) and role (GR) were measured both retrospectively and at the time of study participation, using standardized questionnaires. The main objective of this study was to determine if patterns of OAEs and AEPs correlate with gender in people affected by DSD and in controls. A second objective was to assess if OAE and AEP patterns differed according to degrees of prenatal androgen exposure across groups. Control males, men with DSD, and women with CAH produced fewer spontaneous OAEs (SOAEs) - the male-typical pattern - than control females and women with CAIS. Additionally, the number of SOAEs produced correlated with gender development across all groups tested. Although some sex differences in AEPs were observed between control males and females, AEP measures did not correlate with gender development, nor did they vary according to degrees of prenatal androgen exposure, among people with DSD. Thus, OAEs, but not AEPs, may prove useful as bioassays for assessing early brain exposure to androgens and predicting gender development in people with DSD., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Human subjects performed in several behavioral conditions requiring, or not requiring, selective attention to visual stimuli. Specifically, the attentional task was to recognize strings of digits that had been presented visually. A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE), called the nSFOAE, was collected during the visual presentation of the digits. The segment of the physiological response discussed here occurred during brief silent periods immediately following the SFOAE-evoking stimuli. For all subjects tested, the physiological-noise magnitudes were substantially weaker (less noisy) during the tasks requiring the most visual attention. Effect sizes for the differences were >2.0. Our interpretation is that cortico-olivo influences adjusted the magnitude of efferent activation during the SFOAE-evoking stimulation depending upon the attention task in effect, and then that magnitude of efferent activation persisted throughout the silent period where it also modulated the physiological noise present. Because the results were highly similar to those obtained when the behavioral conditions involved auditory attention, similar mechanisms appear to operate both across modalities and within modalities. Supplementary measurements revealed that the efferent activation was spectrally global, as it was for auditory attention., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In this study, a nonlinear version of the stimulus-frequency OAE (SFOAE), called the nSFOAE, was used to measure cochlear responses from human subjects while they simultaneously performed behavioral tasks requiring, or not requiring, selective auditory attention. Appended to each stimulus presentation, and included in the calculation of each nSFOAE response, was a 30-ms silent period that was used to estimate the level of the inherent physiological noise in the ear canals of our subjects during each behavioral condition. Physiological-noise magnitudes were higher (noisier) for all subjects in the inattention task, and lower (quieter) in the selective auditory-attention tasks. These noise measures initially were made at the frequency of our nSFOAE probe tone (4.0 kHz), but the same attention effects also were observed across a wide range of frequencies. We attribute the observed differences in physiological-noise magnitudes between the inattention and attention conditions to different levels of efferent activation associated with the differing attentional demands of the behavioral tasks. One hypothesis is that when the attentional demand is relatively great, efferent activation is relatively high, and a decrease in the gain of the cochlear amplifier leads to lower-amplitude cochlear activity, and thus a smaller measure of noise from the ear., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Maternal preeclampsia is associated with altered placental development in the first trimester of pregnancy. Confined placental trisomy 16 mosaicism (CPM16) is a genetic abnormality of the placenta that is highly predisposing to preeclampsia. We previously demonstrated widespread alterations in DNA methylation in 3rd trimester placentae associated with chromosomally normal early-onset preeclampsia (EOPET) and questioned whether similar changes would be associated with CPM16, making this condition a potential model for studying EOPET-associated changes early in pregnancy., Methods: Using the Illumina Infinium HumanMethylation450 BeadChip, 3rd trimester CPM16 placental samples (N = 10) were compared to gestational age matched controls, and to 1st trimester trisomy 16 placentae (N = 5)., Results: DNA methylation differences associated with CPM16 were identified at 2254 CpGs using stringent criteria (FDR < 0.01, Δβ > 0.15). A subset of these differences (11%; p < 0.0001) overlapped those observed in chromosomally normal EOPET using similarly stringent criteria (FDR < 0.01; Δβ > 0.125). Importantly, the majority of EOPET-associated CpGs were significantly altered (p < 0.05) in CPM16 with a similar Δβ distribution. This was true for CPM16 with (N = 5) and without (N = 5) EOPET, although EOPET cases showed a tendency towards larger changes. Of the shared CPM16/EOPET associated changes, three CpGs near two genes (ARGHEF37 and JUNB) were also altered in 1st trimester trisomy 16 placentae., Discussion: Despite the limited sample size, widespread DNA methylation changes are observed in Trisomy 16 that overlap those seen previously in chromosomally normal EOPET. Hence, Trisomy 16 may provide a model to study the progression of placental changes that occurs in EOPET across different gestational ages., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In recent years, consumer choice has become an important element of public policy. One reason is that consumers differ in their tastes and needs, which they can express most easily through their own choices. Elements that strengthen consumer choice feature prominently in the design of public insurance markets, for instance in the United States in the recent introduction of prescription drug coverage for older individuals via Medicare Part D. For policy makers who design such a market, an important practical question in the design phase of such a new program is how to deduce enrollment and plan selection preferences prior to its introduction. In this paper, we investigate whether hypothetical choice experiments can serve as a tool in this process. We combine data from hypothetical and real plan choices, elicited around the time of the introduction of Medicare Part D. We first analyze how well the hypothetical choice data predict willingness to pay and market shares at the aggregate level. We then analyze predictions at the individual level, in particular how insurance demand varies with observable characteristics. We also explore whether the extent of adverse selection can be predicted using hypothetical choice data alone., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We study the Medicare Part D prescription drug insurance program as a bellwether for designs of private, non-mandatory health insurance markets, focusing on the ability of consumers to evaluate and optimize their choices of plans. Our analysis of administrative data on medical claims in Medicare Part D suggests that fewer than 25% of individuals enroll in plans that are ex ante as good as the least cost plan specified by the Plan Finder tool made available to seniors by the Medicare administration, and that consumers on average have expected excess spending of about $300 per year, or about 15% of expected total out-of-pocket cost for drugs and Part D insurance. These numbers are hard to reconcile with decision costs alone; it appears that unless a sizeable fraction of consumers place large values on plan features other than cost, they are not optimizing effectively., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Pseudomyxoma peritonei (PMP) is an uncommon but lethal variant of adenocarcinoma. Many recent case series have reported improved survival with the combination of cytoreductive surgery and intraperitoneal chemotherapy (IPEC) in treating PMP. The aim of this study was to analyze the published studies for improved survival with this treatment strategy., Methods: Data from all studies using IPEC in treating PMP were analyzed. We searched PubMed, MEDLINE, and the Cochrane Library (through September 2011). Studies were limited to English and PMP with appendiceal origin. Twenty-nine studies were identified, with 15 studies from different treatment centers that were specifically analyzed for differences in 5-y mortality and morbidity. Observed to expected (OE) ratios were calculated for both mortality and morbidity., Results: Mean and median 3-y, 5-y, and 10-y survival rates were 77.18%/77.85%, 76.63%/79.5%, and 57.3%/55.9%, respectively. Of the 10 studies that had sufficient data to calculate OE ratios from the 5-year mortality data, two had OE ratios lower than 1. Of the 11 studies that had data sufficient to calculate OE ratios from the morbidity data, four had OE ratios that were less than 1., Conclusions: Combining cytoreductive surgery and IPEC improves the survival of patients with PMP, regardless of treatment modality. Although this treatment strategy is associated with an increased risk of morbidity, the increase in survival may be acceptable in proposing an alternative to debulking procedures alone., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The ability of a breast cancer cell to evade apoptosis has a key role in tumor progression and sensitivity to treatment. High levels of Bcl-2-associated X protein (Bax) in tumor cells have been found to promote apoptosis and sensitize cells to anti-cancer therapies. Bcl-2-associated X protein redistribution to the mitochondrial membrane results in the release of proapoptotic factors including cytochrome C, second-mitochondrial-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low PI (Smac/DIABLO), and Ca(2+). We aimed to explore this pathway in cancerous breast cell lines treated with the naturally occurring antioxidant 3,5-dimethoxy-4-hydroxystilbene (pterostilbene)., Methods: We used whole cell lysates +/- Bax SiRNA from the cell lines MCF-7 and MDA-MB-231 in an enzyme-linked immunosorbent assay to quantify Bax, cytochrome C, Smac/DIABLO expression, and manganese superoxide dismutase (MnSOD) activity after treatment with pterostilbene. We quantified cell death using histone-related DNA complexes from cytosolic and mitochondrial fractions and used methylthiazol tetrazolium assay to analyze cell proliferation, in the presence of Bax-silencing or scrambled RNA. We measured changes in cytosolic calcium using the ratiometric calcium-sensitive dye fura-2-AM using an inverted ratiometric monochromator microscope., Results: Treatment of MCF-7 and MDA-MB-231 (MDA) cells with pterostilbene caused concentration-dependent increases in intracellular Bax at all doses tested. RNA silencing of Bax resulted in reduced rates of apoptosis in both cells types and increased cell survival when treated with pterostilbene. We observed an increase in cytochrome C in MDA cells after treatment with pterostilbene. The MCF-7 cells showed a net increase in cytosolic cytochrome C, with a corresponding reduction in mitochondrial cytochrome C after treatment with 50 and 75 μmol/L pterostilbene. We observed this again in Smac/DIABLO expression in both cell types. In MCF-7 cells, pterostilbene treatment caused an increase in cytosolic but a decrease in mitochondrial Smac/DIABLO protein concentrations. Pterostilbene significantly increase MnSOD activity in MDA-MB-231 cells. Finally, pterostilbene resulted in significant increases in cytosolic calcium concentrations., Conclusions: The natural dietary compound pterostilbene has an anti-proliferative effect and induces apoptosis in breast cancer cells in vitro via Bax activation and overexpression, resulting in increased MnSOD, Smac/DIABLO, and cytochrome C activity and cytosolic Ca(2+) overload., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a natural dietary compound and the primary antioxidant component of blueberries. It has increased bioavailability in comparison to other stilbene compounds, which may enhance its dietary benefit and possibly contribute to a valuable clinical effect. Multiple studies have demonstrated the antioxidant activity of pterostilbene in both in vitro and in vivo models illustrating both preventative and therapeutic benefits. The antioxidant activity of pterostilbene has been implicated in anticarcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. In this review, we explore the antioxidant properties of pterostilbene and its relationship to common disease pathways and give a summary of the clinical potential of pterostilbene in the prevention and treatment of various medical conditions.

Background: We have previously demonstrated that pterostilbene, a compound in blueberries, exerts antiproliferative effects against pancreatic adenocarcinoma. However, little is known about the anti-inflammatory effects of pterostilbene in pancreatitis. Therefore, the aim of this study was to evaluate the effect of pterostilbene on inflammatory markers in an in vitro pancreatitis model. We hypothesized that pterostilbene would ameliorate the immediate inflammatory response in tumor necrosis factor alpha (TNF-α)-induced pancreatitis through downregulation of signal transducer and activator of transcription 3 (STAT3) and inhibition of TNF-α-induced secretion of lipase and proinflammatory cytokines interleukins (ILs) 1β and 6., Methods: AR42J acinar cells were pretreated with TNF-α to induce pancreatitis followed by 25 and 50 μM pterostilbene for 15 and 30 min. Secretion of lipase was quantified using a lipase assay and used as a marker of TNF-α-induced pancreatitis. Detection of STAT3, IL-1β, and IL-6 was performed using enzyme-linked immunosorbent assay. Analysis of variance and Tukey post hoc analysis were used for statistical analysis., Results: TNF-α increased the secretion of lipase, IL-1β, and IL-6. Pterostilbene treatment inhibited TNF-α-induced secretion of lipase (P<0.01 and P<0.001), IL-1β (P<0.05), and IL-6 (P<0.05 and P<0.01). Inhibition of STAT3 by pterostilbene occurred with treatment doses of 25 and 50 μM (P<0.001 and P<0.01)., Conclusions: The dietary compound pterostilbene exerts an anti-inflammatory effect in pancreatitis through downregulation of STAT3 and decreased the secretion of lipase, IL-1β, and IL-6. Pterostilbene's amelioration of pancreatitis in vitro makes it an advantageous anti-inflammatory agent. Further studies are necessary to determine pterostilbene's role as a protective or therapeutic agent in pancreatitis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Infant mortality in British Columbia (BC) First Nations remains elevated relative to other residents. The p.P479L (c.1436C>T) variant of carnitine palmitoyltransferase 1 (CPT1A) is frequent in some aboriginal populations and may be associated with increased infant deaths. This work was initiated to determine the performance of acylcarnitine profiling for detecting this variant, to determine its frequency in BC, and to determine if it is associated with sudden infant deaths in this population., Methods: Newborn screening cards from all BC First Nations infants in 2004 and all sudden unexpected deaths in BC First Nations infants (1999-2009) were genotyped for the CPT1A p.P479L variant and linked to archival acylcarnitine data., Results: The CPT1A p.P479L variant is frequent in BC First Nations but is not evenly distributed, with higher rates in coastal regions (up to 25% homozygosity) with historically increased infant mortality. There is also an overrepresentation of p.P479L homozygotes in unexpected infant deaths from these regions, with an odds ratio of 3.92 (95% confidence interval: 1.69-9.00). Acylcarnitine profiling will identify p.P479L homozygotes with a 94% sensitivity and specificity., Conclusions: The CPT1A p.P479L variant is common to some coastal BC First Nations, and homozygosity for this variant is associated with unexpected death in infancy. The high frequency of this variant in a wide range of coastal aboriginal communities, however, suggests a selective advantage, raising the possibility that this variant may have differing impacts on health depending on the environmental or developmental context.

Background: Postmarketing reports have linked exenatide use with acute pancreatitis and pancreatic cancer, but a definitive relationship has yet to be established., Subjects and Methods: We conducted a retrospective cohort analysis of patients with type 2 diabetes with employer-provided health insurance from 2007 to 2009. Multivariate models estimated the association between exenatide use and acute pancreatitis and pancreatic cancer. We required at least 1 year of exenatide exposure in the pancreatic cancer analysis. Sensitivity analyses were conducted that quasirandomized exenatide use based on patient out-of-pocket costs., Results: Among 268,561 patients included in the acute pancreatitis analysis, only 2.6% used exenatide. Hospitalization for acute pancreatitis was rare (0.247% of patients). In unadjusted and adjusted analyses, patients who did not use exenatide were more likely to be hospitalized for acute pancreatitis (0.249% vs. 0.196% in unadjusted analysis), but the difference was not statistically significant in either analysis (P = 0.22 and P = 0.70, respectively). Among 209,306 patients in the pancreatic cancer analysis, 0.070% were diagnosed with pancreatic cancer, and 0.88% had at least 1 year of continuous exenatide exposure prior to the diagnosis. Those with exenatide exposure had higher rates of pancreatic cancer compared with those without (0.081% vs. 0.070% in unadjusted analysis). In both unadjusted and adjusted analyses, the difference was not statistically significant (P = 0.80 and P = 0.46, respectively). In sensitivity analyses, results were similar., Conclusions: We found no association between exenatide use and either hospitalization for acute pancreatitis or pancreatic cancer in a large sample of privately insured U.S. patients.

Both distortion-product otoacoustic emissions (DPOAEs) and performance in an auditory-masking task involving combination tones were measured in the same frequency region in the same ears. In the behavioral task, a signal of 3.6 kHz (duration 300 ms, rise/fall time 20 ms) was masked by a 3.0-kHz tone (62 dB SPL, continuously presented). These two frequencies can produce a combination tone at 2.4 kHz. When a narrowband noise (2.0-2.8 kHz, 17 dB spectrum level) was added as a second masker, detection of the 3.6-kHz signal worsened by 6-9 dB (the Greenwood effect), revealing that listeners had been using the combination tone at 2.4 kHz as a cue for detection at 3.6 kHz. Several outcomes differed markedly by sex and racial background. The Greenwood effect was substantially larger in females than in males, but only for the White group. When the magnitude of the Greenwood effect was compared with the magnitude of the DPOAE measured in the 2.4 kHz region, the correlations typically were modest, but were high for Non-White males. For many subjects, then, most of the DPOAE measured in the ear canal apparently is not related to the combination-tone cue that is masked by the narrowband noise.

Brief tones of 1.0 and 8.0 kHz were used to evoke auditory brainstem responses (ABRs), and the differences between the wave-V latencies for those two frequencies were used as a proxy for cochlear length. The tone bursts (8 ms in duration including 2-ms rise/fall times, and 82 dB in level) were, or were not, accompanied by a continuous, moderately intense noise band, highpass filtered immediately above the tone. The proxy values for length were compared with various measures of otoacoustic emissions (OAEs) obtained from the same ears. All the correlations were low, suggesting that cochlear length, as measured by this proxy at least, is not strongly related to the various group and individual differences that exist in OAEs. Female latencies did not differ across the menstrual cycle, and the proxy length measure exhibited no sex difference (either for menses females vs. males or midluteal females vs. males) when the highpass noises were used. However, when the subjects were partitioned into Whites and Non-Whites, a substantial sex difference in cochlear length did emerge for the White group, although the correlations with OAEs remained low. Head size was not highly correlated with any of the ABR measures., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: To investigate the inhibitory role of pterostilbene in pancreatic cancer, we conducted a genomic analysis of pterostilbene-treated pancreatic cancer cells. We also investigated the effect of pterostilbene upon the carcinogenic markers, manganese superoxide dismutase, cytochrome C, Smac/DIABLO, and STAT3 phosphorylation in vitro. The antiproliferative effects of pterostilbene were further evaluated in an in vivo model., Methods: Pancreatic cancer cells were treated with pterostilbene and evaluated with DNA microarray analysis. Pterostilbene-treated cells were analyzed for cytochrome C, Smac/DIABLO, manganese superoxide dismutase (MnSOD)/antioxidant activity, and STAT3 phosphorylation using ELISA. Data were statistically analyzed using ANOVA. Pterostilbene was then administered to nude mice for 8 weeks, and tumor growth rates were recorded and statistically analyzed., Results: Microarray analysis of pterostilbene-treated cells revealed upregulation of pro-apoptosis genes. In vitro, pterostilbene treatment altered levels of phosphorylated STAT3, MnSOD/antioxidant activity, cytochrome C, and Smac/DIABLO. In nude mice, oral pterostilbene inhibited tumor growth rates., Conclusion: Pterostilbene alters gene expression in pancreatic cancer and increases the antiproliferative markers cytochrome C, Smac/DIABLO, and MnSOD/antioxidant activity. It was also shown to inhibit phosphorylated STAT3, a marker of accelerated tumorigenesis, and decrease pancreatic tumor growth in vivo. Further studies are warranted to elucidate the effects of pterostilbene in humans.

Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is an antioxidant that is primarily found in blueberries. Studies suggest that pterostilbene exhibits the hallmark characteristics of an effective anticancer agent based on its antineoplastic properties in several common malignancies. In vitro models have shown that pterostilbene inhibits cancer growth through alteration of the cell cycle, induction of apoptosis, and inhibition of metastasis. In vivo, pterostilbene inhibits tumorigenesis and metastasis with negligible toxicity. Pterostilbene has also been shown to be effective as an inducer of antioxidant capacity in multiple cancer cell lines that may facilitate its function as an anticarcinogenic compound. Additionally, preliminary studies show that pterostilbene exhibits much greater bioavailability compared with other stilbene compounds; however the exact pharmacologic mechanism of pterostilbene and its effects in humans are still under investigation. In this review, we present a comprehensive summary of the antineoplastic mechanisms of pterostilbene based on the results of preclinical studies and highlight recent advances in the study of this dietary compound., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The hormone leptin is implicated in breast carcinogenesis in obese women. One mechanism is through its activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT3) and apoptosis dysregulation. We have shown that the antioxidant pterostilbene inhibits proliferation and induces apoptosis in breast cancer. Therefore, the goal of this study was to evaluate the effect of pterostilbene on cell proliferation and JAK/STAT3 signaling in leptin-stimulated breast cancer., Methods: Breast cancer cells were treated with leptin alone or in combination with pterostilbene. Detection of cell proliferation and JAK/STAT3 signaling were performed using enzyme-linked immunosorbent assay protocols. Statistical analysis was performed with analysis of variance and Tukey post hoc analysis., Results: Pterostilbene suppresses constitutive as well as leptin-induced JAK/STAT3 activation. Pterostilbene treatment also inhibited leptin-induced cell proliferation., Conclusions: Pterostilbene has an inhibitory effect on leptin-stimulated breast cancer in vitro through reduction of cell proliferation and JAK/STAT3 signaling, a critical regulatory component of tumorigenesis in obesity-related breast cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Context: With widespread interest in natural remedies and "wholistic" treatments, there has been a renewed focus on the impact of spirituality related alternative therapy for many current chronic diseases., Objective: To assess the potential impact of spiritual beliefs on lifestyle choices such as tobacco use, we conducted a patient survey., Design/setting: This cross-section study was conducted using a 27-question survey of patients seen at the Mayo Clinic over a 14-week period., Patients: We invited all patients (smokers and nonsmokers) seen in several Mayo Clinic divisions to participate in this voluntary survey., Interventions: The survey included demographic information, history of tobacco use or nonuse, and assessment of spirituality., Main Outcome Measure: Among the 501 patients who participated, 370 were nonsmokers and 131 were smokers. Compared with smokers, nonsmokers more often participated in religious activities such as regular weekly church attendance (48% vs. 24%), daily prayer, and Bible study (49% vs. 24%; P < .001). Current smoking was negatively correlated with religious activities. However, after adjustment for demographic factors, there was no significant difference in intrinsic spirituality (importance of religion) between the two groups (P < .130)., Result: Nonsmokers are more likely to engage in religious activities such as prayer, Bible study, and regular church attendance. Further studies may be helpful to clearly define the potential impact of spirituality on smoking cessation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We describe respiratory chain complex IV deficiency (cytochrome c oxidase deficiency) in a female infant with a neonatal rapidly progressive fatal course characterized by microcephaly, encephalopathy, persistent lactic acidosis, and hypertrophic cardiomyopathy. Postmortem cardiac muscle study showed marked complex IV deficiency. In contrast, complex IV activity was only slightly decreased in the skeletal muscle. Subsequent molecular investigations showed compound heterozygosity for two known pathogenic mutations in the COX15 gene. We compare the findings in our patient to those of the three previously reported cases., (Copyright © 2011 Wiley-Liss, Inc.)

The auditory system exhibits differences by sex and by sexual orientation, and the implication is that relevant auditory structures are altered during prenatal development, possibly by exposure to androgens. The otoacoustic emissions (OAEs) of newborn male infants are weaker than those of newborn females, and these sex differences persist through the lifespan. The OAEs of nonheterosexual females also are weaker than those of heterosexual females, suggesting an atypically strong exposure to androgens some time early in development. Auditory evoked potentials (AEPs) also exhibit sex differences beginning early in life. Some AEPs are different for heterosexual and nonheterosexual females, and other AEPs are different for heterosexual and nonheterosexual males. Research on non-humans treated with androgenic or anti-androgenic agents also suggests that OAEs are masculinized by prenatal exposure to androgens late in gestation. Collectively, the evidence suggests that prenatal androgens, acting globally or locally, affect both nonheterosexuality and the auditory system., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In this study we estimate the reliability of reflex response variables to identify the main sources of variability and to estimate appropriate measurement strategies to obtain more reliable measures. Back muscle surface electromyography (EMG) was recorded in healthy males during anteriorly-directed sudden loading perturbations applied to the trunk. Measures of EMG reflex latency and amplitude were obtained. The generalizability theory was used as a framework to estimate the magnitude of the different variance components and the reliability of the measures corresponding to various simulations of different measurement strategies. Reliability of the different variables was poor to moderate (intraclass correlation coefficient range 0-0.62). Averaging scores across homologous muscles and several trials were strategies to achieve more acceptable reliability. The reflex response of back muscles is inherently variable, and a large measurement effort is necessary to obtain reliable and, consequently, valid and responsive estimations of this neuromuscular function., (Copyright © 2011 Wiley Periodicals, Inc.)

An imbalance of imprinted gene expression within 11p15.5 is observed in Beckwith-Wiedemann syndrome (BWS), as well as in a variety of placental abnormalities including complete hydatidiform mole (CHM), placental mesenchymal dysplasia (PMD) and triploidy. To facilitate the diagnosis of epigenetic errors and chromosomal imbalance of 11p15.5, we validated a pyrosequencing assay to measure methylation at KvDMR1 using blood samples from 13 BWS cases, 8 of which showed reduced methylation as compared to control blood. An imbalance between maternal and paternal genomes as is found in triploidy, CHM or PMD was also associated with altered KvDMR1 methylation. A reciprocal pattern of methylation was obtained in the triploid cases by assaying the proximal 11p15.5 ICR associated with H19. To distinguish chromosome 11 specific alterations from whole genome imbalance, other imprinted differentially methylated regions (DMRs) can be utilized. Thus, pyrosequencing assays for DMRs associated with SGCE, SNRPN, and MEST were also compared for their utility in diagnosing parental imbalance in placental samples. While each of these assays could successfully distinguish parental origin of triploidy, SGCE showed the clearest separation between groups. The combined use of a chromosome 11p15.5 assay (e.g. KvDMR1 or H19-ICR) and non-chromosome 11 assay (e.g. SGCE) provides a potentially valuable diagnostic tool in the rapid screening of methylation errors in placental disorders. These results also show the maintenance of imprinting status at these loci in the human placenta, even in the presence of abnormal pathology., (© 2010 John Wiley & Sons A/S.)

Auditory evoked potential (AEP) data from two studies originally designed for other purposes were reanalyzed. The auditory brainstem response (ABR), middle-latency response (MLR), and long-latency response (LLR) were measured. The latencies to each of several peaks were measured for each subject for each ear of click presentation, and the time intervals between successive peaks were calculated. Of interest were differences in interpeak intervals between the sexes, between people of differing sexual orientations, and between the two ears of stimulation. Most of the differences obtained were small. The largest sex differences were for interval I → V in the ABR and interval N1 → N2 of the LLR (effect sizes > 0.6). The largest differences between heterosexuals and nonheterosexuals were for the latency to Wave I in both sexes, for the interval Na → Nb in females, and for intervals V → Na and Nb → N1 in males (effect sizes > 0.3). The largest difference for ear stimulated was for interval N1 → N2 in heterosexual females (effect size ∼0.5). No substantial differences were found in the AEP intervals between women using, and not using, oral contraceptives. Left/right correlations for the interpeak intervals were mostly between about 0.4 and 0.6. Correlations between the ipsilateral intervals were small; i.e., interval length early in the AEP series was not highly predictive of interval length later in the series. Interpeak intervals appear generally less informative than raw latencies about differences by sex and by sexual orientation., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background: Tamoxifen is widely used for the treatment of breast cancer. Pterostilbene, a bioavailable stilbenoid found in blueberries, has been found to inhibit breast cancer growth in vitro. It was hypothesized that combining pterostilbene with tamoxifen would produce additive effects on estrogen receptor-positive breast cancer cells., Methods: Two estrogen receptor-positive breast cancer cell lines, MCF7 and ZR-751, were pretreated with graduated doses of pterostilbene for 24 hours, followed by 5 μmol/L tamoxifen. MTT proliferation assays and Cell Death Detection ELISA(PLUS) tests evaluated cell viability and apoptosis., Results: MCF7 cells showed inhibition (10 and 20 μmol/L, P < .001; 30 μmol/L, P < .05) at all time points when combined with tamoxifen. ZR-751 cells showed additive reductions in cell viability (P < .001). Cell Death Detection ELISA(PLUS) indicated increased apoptosis (P < .01)., Conclusions: Pterostilbene shows an additive inhibitory effect on breast cancer cells when combined with tamoxifen, most likely from augmented cancer cell apoptosis., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The detectability of a 10-ms tone masked by a 400-ms wideband noise was measured as a function of the delay in the onset of the tone compared to the onset of the noise burst. Unlike most studies like this on auditory overshoot, special attention was given to signal delays between 0 and 45 ms. Nine well-practiced subjects were tested using an adaptive psychophysical procedure in which the level of the masking noise was adjusted to estimate 79% correct detections. Tones of both 3.0 and 4.0 kHz, at different levels, were used as signals. For the subjects showing overshoot, detectability remained approximately constant for at least 20-30 ms of signal delay, and then detectability began to improve gradually toward its maximum at about 150-200 ms. That is, there was a "hesitation" prior to detectability beginning to improve, and the duration of this hesitation was similar to that seen in physiological measurements of the medial olivocochlear (MOC) system. This result provides further support for the hypothesis that the MOC efferent system makes a major contribution to overshoot in simultaneous masking.

A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE) was measured using stimulus waveforms similar to those used for behavioral overshoot. Behaviorally, the seven listeners were as much as 11 dB worse at detecting a brief tonal signal (4.0 kHz, 10 ms in duration) when it occurred soon after the onset of a wideband masking noise (0.1-6.0 kHz; 400 ms in duration) than when it was delayed by about 200 ms, and the nonlinear SFOAE measure exhibited a similar effect. When either lowpass (0.1-3.8 kHz) or bandpass noise (3.8-4.2 kHz) was used instead of the wideband noise, the physiological and behavioral measures again were similar. When a highpass noise (4.2-6.0 kHz) was used, the physiological and behavioral measures both showed no overshoot-like effect for five of the subjects. The physiological response to the tone decayed slowly after the termination of the noise, much like the time course of resetting for behavioral overshoot. One subject exhibited no overshoot behaviorally even though his cochlear responses were like those of the other subjects. Overall, the evidence suggests that some basic characteristics of overshoot are obligatory consequences of cochlear function, as modulated by the olivocochlear efferent system., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

A procedure for extracting the nonlinear component of the stimulus-frequency otoacoustic emission (SFOAE) is described. This nSFOAE measures the amount by which the cochlear response deviates from linear additivity when the input stimulus is doubled in amplitude. When a 4.0-kHz tone was presented alone, the magnitude of the nSFOAE response remained essentially constant throughout the 400-ms duration of the tone; response magnitude did increase monotonically with increasing tone level. When a wideband noise was presented alone, nSFOAE magnitude increased over the initial 100- to 200-ms portion of the 400-ms duration of the noise. When the tone and the wideband noise were presented simultaneously, nSFOAE magnitude decreased momentarily, then increased substantially for about the first 100 ms and then remained strong for the remainder of the presentation. Manipulations of the noise bandwidth revealed that the low-frequency components were primarily responsible for this rising, dynamic response; no rising segment was seen with bandpass or highpass noise. The rising, dynamic nSFOAE response is likely attributable to activation of the medial olivocochlear efferent system. This perstimulatory emission appears to have the potential to provide information about the earliest stages of auditory processing for stimuli commonly used in psychoacoustical tasks.

Congenital brain tumors are rare. Clinically, they often result in macrocrania, hydrocephalus, and focal neurologic deficits. Fetal onset may result in dystocia and stillbirth. Antenatal detection is becoming more common as the result of neuroimaging, and modalities such as magnetic resonance imaging can assist in narrowing the pathologic differential diagnoses. Teratomas and astrocytomas appear to be the most common congenital neoplasms. Amongst the latter, all grades and many subtypes are represented in the congenital time period, including the diffusely infiltrative forms of astrocytoma. Gliosarcoma is currently considered a variant of glioblastoma (i.e., astrocytoma, World Health Organization grade IV) that exhibits genetically similar yet phenotypically separate histologic regions of high-grade astrocytoma and sarcoma. Only rare instances of congenital gliosarcoma have been reported. We detail the case of a 1-day-old term male who presented with macrocrania, hydrocephalus, and signs of increased intracranial pressure. Pathology revealed evidence of a classic gliosarcoma.

Otoacoustic emissions (OAEs) differ between the sexes in humans, rhesus and marmoset monkeys, and sheep. OAEs also are different in a number of special populations of humans. Those basic findings are reviewed and discussed in the context of possible prenatal-androgen effects on the auditory system. A parsimonious explanation for several outcomes is that prenatal exposure to high levels of androgens can weaken the cochlear amplifiers and thereby weaken otoacoustic emissions (OAEs). Prenatal androgen exposure apparently also can alter auditory evoked potentials (AEPs). Some non-hormonal factors possibly capable of producing sex and group differences are discussed, and some speculations are offered about specific cochlear structures that might differ between the two sexes.

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges.

Background: Previous research has revealed that the ratios of the lengths of various pairs of human fingers differ in males and females., Method: In an attempt to determine whether parallel sex differences also exist in the relative lengths of human metacarpals and metatarsals, the lengths of the metapodials for both hands and both feet were measured in a collection of human skeletons. For each hand and each foot, all of the 10 possible pairwise ratios for length of the five metapodials were calculated., Results: For the skeletons of European/Caucasian extraction (Ns=89 males, 50 females), there were substantial sex differences for several of the metacarpal-length ratios, but the pattern was not identical with the pattern previously reported for human fingers. Namely, the largest sex differences were for the three ratios involving metacarpal 5 on the left hand, while the sex difference for the ratio comparing the second and fourth metacarpals (the comparison commonly showing the largest sex difference for fingers) was small and non-significant for both hands in these European-Americans. For the skeletons of African extraction (Ns=65 males, 55 females), no sex differences were found in any of the 20 metacarpal-length ratios. This outcome was unexpected because past research had shown sex differences in finger-length ratios for people of African extraction. For metatarsals, none of the 20 ratios exhibited a substantial sex difference for either group of skeletons., Conclusions: A discrepancy apparently exists between the length ratios based on fingers and those based on metacarpals.

Otoacoustic emissions (OAEs) were measured in male and female Suffolk sheep (Ovis aries). Some sheep had been administered androgens or estrogens during prenatal development, some were gonadectomized after birth, and some were allowed to develop normally. As previously reported for spotted hyenas, gonadectomy did not alter the OAEs for either sex; accordingly, the untreated/intact and the untreated/gonadectomized animals were pooled to form the control groups. The click-evoked otoacoustic emissions (CEOAEs) exhibited by the female control group (N=12) were slightly stronger (effect size=0.42) than those in the male control group (N=15), which is the same direction of effect reported for humans and rhesus monkeys. Females administered testosterone prenatally (N=16) had substantially weaker (masculinized) CEOAEs than control females (effect size=1.15). Both of these outcomes are in accord with the idea that prenatal exposure to androgens weakens the cochlear mechanisms that underlie the production of OAEs. The CEOAEs of males administered testosterone prenatally (N=5) were not different from those of control males, an outcome also seen in similarly treated rhesus monkeys. Males administered dihydrotestosterone (DHT) prenatally (N=3) had slightly stronger (hypo-masculinized) CEOAEs than control males. No spontaneous otoacoustic emissions (SOAEs) were found in any ears, a common finding in non-human species. To our knowledge, this is the first ruminant species measured for OAEs.

Although several studies have documented the existence of sex differences in spontaneous otoacoustic emissions (SOAEs) and transient-evoked OAEs (TEOAEs) in humans, less has been published about sex differences in distortion-product OAEs (DPOAEs). Estimates of sex and ear differences were extracted from a data set of OAE measurements previously collected for other purposes. In accord with past findings, the sex differences for TEOAEs were substantial for both narrowband and wideband measures. By contrast, the sex differences for DPOAEs were about half the size of those for TEOAEs. In this sample, the ear differences were small for TEOAEs in both sexes and absent for DPOAEs. One implication is that the cochlear mechanisms underlying DPOAEs appear to be less susceptible to whatever influences are responsible for producing sex differences in TEOAEs and SOAEs in humans. We discuss the possibility that differences in the effective level of the stimuli may contribute to these outcomes.

Distortion-product otoacoustic emissions (DPOAEs) were weak or absent in about one-third of sheep (Ovis aries) of both sexes tested for otoacoustic emissions (OAEs) even though their click-evoked OAEs (CEOAEs) seemingly were typical of other sheep of the same sex. Various pieces of evidence suggest that the absence of measurable DPOAEs was unlikely to be attributable to anesthetic effects, a poorly located probe tip, a pressure differential between middle and outer ears, season of the year, body position during testing, temperature effects, or previous medical history. Sheep apparently can exhibit a marked dissociation between DPOAEs and CEOAEs. In those sheep having measurable DPOAEs, the DPOAEs were stronger in males than in females, which is the opposite direction of effect from the CEOAEs measured in these same sheep and in humans. In female sheep exposed to higher-than-normal levels of androgens during gestation, the measurable DPOAEs were stronger than in untreated females. Although this also was the opposite direction of effect from expected, it still was a shift in the male direction, in accord with past findings about the masculinizing effects of androgens on OAEs. In sheep, androgen exposure appears to have different effects on the mechanisms underlying DPOAEs from those underlying CEOAEs.

Distortion-product otoacoustic emissions (DPOAEs) were measured in a New World primate, the common marmoset (Callithrix jacchus). We determined the optimal primary-tone frequency ratio (f(2)/f(1)) to generate DPOAEs of maximal amplitude between 3 and 24 kHz. The optimal f(2)/f(1), determined by varying f(2)/f(1) from 1.02 to 1.40 using equilevel primary tones, decreased with increasing f(2) frequency between 3 and 17 kHz, and increased at 24 kHz. The optimal f(2)/f(1) ratio increased with increasing primary-tone levels from 50 to 74 dB SPL. When all stimulus parameters were considered, the mean optimal f(2)/f(1) was 1.224-1.226. Additionally, we determined the effect of reducing L(2) below L(1). Decreasing L(2) below L(1) by 0, 5, and 10 dB (f(2)/f(1)=1.21) minimally affected DPOAE strength. DPOAE levels were stronger in females than males and stronger in the right ear than the left, just as in humans. This study is the first to measure OAEs in the marmoset, and the results indicate that the effect of varying the frequency ratio and primary-tone level difference on marmoset DPOAEs is similar to the reported effects in humans and Old World primates.

Snail family proteins are key regulators of epithelial-mesenchymal transition, but their role in endothelial-to-mesenchymal transition (EMT) is less well studied. We show that Slug, a Snail family member, is expressed by a subset of endothelial cells as well as mesenchymal cells of the atrioventricular canal and outflow tract during cardiac cushion morphogenesis. Slug deficiency results in impaired cellularization of the cardiac cushion at embryonic day (E)-9.5 but is compensated by increased Snail expression at E10.5, which restores cardiac cushion EMT. We further demonstrate that Slug, but not Snail, is directly up-regulated by Notch in endothelial cells and that Slug expression is required for Notch-mediated repression of the vascular endothelial cadherin promoter and for promoting migration of transformed endothelial cells. In contrast, transforming growth factor beta (TGF-beta) induces Snail but not Slug. Interestingly, activation of Notch in the context of TGF-beta stimulation results in synergistic up-regulation of Snail in endothelial cells. Collectively, our data suggest that combined expression of Slug and Snail is required for EMT in cardiac cushion morphogenesis.

During the past two decades, there has been a remarkable increase in the availability and utility of tumor markers and tumor genetics in the diagnosis, and management of the various GI malignancies. Still, there is considerable variability among physicians in the use of followup studies following potentially curative resection of any of the GI cancers. Multiple surveillance strategies have been published at cost ranging from a few hundred to several thousand dollars per patient. Therefore, the literature on the currently available GI tumor markers, will be reviewed. Those tumor markers can be tested and detected basically in one of two clinical settings: (a) serum-based; in serum specimens, and (b) tissue-based; in endoscopic and surgical specimens.

The otoacoustic emissions (OAEs) measured in a collection of special populations of humans and certain nonhuman species suggest that OAEs may provide a window into some processes of human prenatal development and sexual differentiation. For reasons that are unclear, OAEs appear to be highly sensitive to events occurring during prenatal development that seem to be related to the degree of exposure to androgens a fetus receives. The (largely circumstantial) evidence for a relationship between androgen exposure and OAE strength comes from a series of studies of twins, children with attention-deficit/hyperactivity disorder, people of differing sexual orientations, and spotted hyenas, among others. Some conclusions are bolstered by parallel studies using auditory evoked potentials (AEPs). OAEs and AEPs are simple, objective, noninvasive measures that appear to have potential as tools of value to researchers working on a wide variety of basic and applied topics beyond audition., (© 2008 Association for Psychological Science.)

We report on the 46th patient with Schinzel-Giedion syndrome (SGS) and the first observation of splenopancreatic fusion in this syndrome. In the antenatal period, a male fetus was found to have bilateral hydronephrosis. Postnatally, in keeping with a diagnosis of SGS, there were large fontanelles, ocular hypertelorism, a wide, broad forehead, midface retraction, a short, upturned nose, macroglossia, and a short neck. Other anomalies included cardiac defects, widened and dense long bone cortices, cerebral ventriculomegaly, and abnormal fundi. Splenopancreatic fusion, usually encountered in trisomy 13, was found on autopsy. Schinzel-Giedion syndrome is likely a monogenic condition for which neither the heritability pattern nor pathogenesis has yet been determined. A clinical diagnosis may be made by identifying the facial phenotype, including prominent forehead, midface retraction, and short, upturned nose, plus one of either of the two other major distinguishing features: typical skeletal abnormalities or hydronephrosis. Typical skeletal anomalies include a sclerotic skull base, wide supraoccipital-exoccipital synchondrosis, increased cortical density or thickness, and broad ribs. Other highly supportive features include neuroepithelial tumors (found in 17%), hypertrichosis, and brain abnormalities. Severe developmental delay and poor survival are constant features in reported patients., (2008 Wiley-Liss, Inc.)

Ambulatory assessment of trunk posture is important in improving our understanding of the risk of low back injury. Recently, small inertial sensors combining accelerometers, gyroscopes and magnetometers were developed and appear to be promising for measuring human movement. However, the validity of such sensors for assessing three-dimensional (3D) trunk posture in motion has not been documented. The purpose of this study was to evaluate a hybrid system (HS) composed of two inertial sensors for the 3D measurement of trunk posture. A secondary purpose was to explore the utility of adding another source of information, a potentiometer, to measure the relative rotation between both sensors in order to improve the validity of the system. The first sensor was placed over the sacrum and the second on the upper part of the thorax. Both sensors were linked by a flexible rod with a potentiometer. A complementary quaternion filter algorithm was used to estimate trunk orientation by taking advantage of the nine components of each sensor and the potentiometer. The HS's orientations were compared to those obtained from a 3D optoelectronic system. Validation of the HS was performed in three steps in which six subjects had to perform manual handling tasks in: (1) static postures; (2) dynamic motions of short duration (30s); and (3) dynamic motions of long duration (30min). The results showed that the root mean square (RMS) error of the HS was generally below 3 degrees for the flexion and lateral bending axes, and less than 6 degrees for the torsion axis, and that this error was lower for the short-duration tests compared to the long-duration one. The potentiometer proved to be an essential addition, particularly when the magnetometer signals were corrupted and only the gyroscope and accelerometer could be combined. It is concluded that the HS can be a useful tool for quantifying 3D trunk posture in motion.