Increasing Iron and Zinc in Pre-Menopausal Women and Its Effects on Mood and Cognition: A Systematic Review.

Iron and zinc are essential minerals often present in similar food sources. In addition to the adverse effects of frank iron and zinc-deficient states, iron insufficiency has been associated with impairments in mood and cognition. This paper reviews current literature on iron or zinc supplementation and its impact on mood or cognition in pre-menopausal women. Searches included MEDLINE complete, Excerpta Medica Database (EMBASE), psychINFO, psychARTICLES, pubMED, ProQuest Health and Medical Complete Academic Search complete, Scopus and ScienceDirect. Ten randomized controlled trials and one non-randomized controlled trial were found to meet the inclusion criteria. Seven studies found improvements in aspects of mood and cognition after iron supplementation. Iron supplementation appeared to improve memory and intellectual ability in participants aged between 12 and 55 years in seven studies, regardless of whether the participant was initially iron insufficient or iron-deficient with anaemia. The review also found three controlled studies providing evidence to suggest a role for zinc supplementation as a treatment for depressive symptoms, as both an adjunct to traditional antidepressant therapy for individuals with a diagnosis of major depressive disorder and as a therapy in its own right in pre-menopausal women with zinc deficiency. Overall, the current literature indicates a positive effect of improving zinc status on enhanced cognitive and emotional functioning. However, further study involving well-designed randomized controlled trials is needed to identify the impact of improving iron and zinc status on mood and cognition

Determinants of Bone and Blood Lead Levels among Minorities Living in the Boston Area

We measured blood and bone lead levels among minority individuals who live in some of Boston’s neighborhoods with high minority representation. Compared with samples of predominantly white subjects we had studied before, the 84 volunteers in this study (33:67 male:female ratio; 31–72 years of age) had similar educational, occupational, and smoking profiles and mean blood, tibia, and patella lead levels (3 μg/dL, 11.9 μg/g, and 14.2 μg/g, respectively) that were also similar. The slopes of the univariate regressions of blood, tibia, and patella lead versus age were 0.10 μg/dL/year (p < 0.001), 0.45 μg/g/year (p < 0.001), and 0.73 μg/g/year (p < 0.001), respectively. Analyses of smoothing curves and regression lines for tibia and patella lead suggested an inflection point at 55 years of age, with slopes for subjects ≥ 55 years of age that were not only steeper than those of younger subjects but also substantially steeper than those observed for individuals > 55 years of age in studies of predominantly white participants. This apparent racial disparity at older ages may be related to differences in historic occupational and/or environmental exposures, or possibly the lower rates of bone turnover that are known to occur in postmenopausal black women. The higher levels of lead accumulation seen in this age group are of concern because such levels have been shown in other studies to predict elevated risks of chronic disease such as hypertension and cognitive dysfunction. Additional research on bone lead levels in minorities and their socioeconomic and racial determinants is needed

A simulation study for comparing testing statistics in response-adaptive randomization

<p>Abstract</p> <p>Background</p> <p>Response-adaptive randomizations are able to assign more patients in a comparative clinical trial to the tentatively better treatment. However, due to the adaptation in patient allocation, the samples to be compared are no longer independent. At large sample sizes, many asymptotic properties of test statistics derived for independent sample comparison are still applicable in adaptive randomization provided that the patient allocation ratio converges to an appropriate target asymptotically. However, the small sample properties of commonly used test statistics in response-adaptive randomization are not fully studied.</p> <p>Methods</p> <p>Simulations are systematically conducted to characterize the statistical properties of eight test statistics in six response-adaptive randomization methods at six allocation targets with sample sizes ranging from 20 to 200. Since adaptive randomization is usually not recommended for sample size less than 30, the present paper focuses on the case with a sample of 30 to give general recommendations with regard to test statistics for contingency tables in response-adaptive randomization at small sample sizes.</p> <p>Results</p> <p>Among all asymptotic test statistics, the Cook's correction to chi-square test (<it>T</it>_<it>MC</it>) is the best in attaining the nominal size of hypothesis test. The William's correction to log-likelihood ratio test (<it>T</it>_<it>ML</it>) gives slightly inflated type I error and higher power as compared with <it>T</it>_<it>MC</it>, but it is more robust against the unbalance in patient allocation. <it>T</it>_{<it>MC </it>}and <it>T</it>_{<it>ML </it>}are usually the two test statistics with the highest power in different simulation scenarios. When focusing on <it>T</it>_{<it>MC </it>}and <it>T</it>_<it>ML</it>, the generalized drop-the-loser urn (GDL) and sequential estimation-adjusted urn (SEU) have the best ability to attain the correct size of hypothesis test respectively. Among all sequential methods that can target different allocation ratios, GDL has the lowest variation and the highest overall power at all allocation ratios. The performance of different adaptive randomization methods and test statistics also depends on allocation targets. At the limiting allocation ratio of drop-the-loser (DL) and randomized play-the-winner (RPW) urn, DL outperforms all other methods including GDL. When comparing the power of test statistics in the same randomization method but at different allocation targets, the powers of log-likelihood-ratio, log-relative-risk, log-odds-ratio, Wald-type Z, and chi-square test statistics are maximized at their corresponding optimal allocation ratios for power. Except for the optimal allocation target for log-relative-risk, the other four optimal targets could assign more patients to the worse arm in some simulation scenarios. Another optimal allocation target, <it>R</it>_{<it>RSIHR</it>}, proposed by Rosenberger and Sriram (<it>Journal of Statistical Planning and Inference</it>, 1997) is aimed at minimizing the number of failures at fixed power using Wald-type Z test statistics. Among allocation ratios that always assign more patients to the better treatment, <it>R</it>_{<it>RSIHR </it>}usually has less variation in patient allocation, and the values of variation are consistent across all simulation scenarios. Additionally, the patient allocation at <it>R</it>_{<it>RSIHR </it>}is not too extreme. Therefore, <it>R</it>_{<it>RSIHR </it>}provides a good balance between assigning more patients to the better treatment and maintaining the overall power.</p> <p>Conclusion</p> <p>The Cook's correction to chi-square test and Williams' correction to log-likelihood-ratio test are generally recommended for hypothesis test in response-adaptive randomization, especially when sample sizes are small. The generalized drop-the-loser urn design is the recommended method for its good overall properties. Also recommended is the use of the <it>R</it>_{<it>RSIHR </it>}allocation target.</p

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

The Epidemiology of Lead Toxicity in Adults: Measuring Dose and Consideration of Other Methodologic Issues

We review several issues of broad relevance to the interpretation of epidemiologic evidence concerning the toxicity of lead in adults, particularly regarding cognitive function and the cardiovascular system, which are the subjects of two systematic reviews that are also part of this mini-monograph. Chief among the recent developments in methodologic advances has been the refinement of concepts and methods for measuring individual lead dose in terms of appreciating distinctions between recent versus cumulative doses and the use of biological markers to measure these parameters in epidemiologic studies of chronic disease. Attention is focused particularly on bone lead levels measured by K-shell X-ray fluorescence as a relatively new biological marker of cumulative dose that has been used in many recent epidemiologic studies to generate insights into lead’s impact on cognition and risk of hypertension, as well as the alternative method of estimating cumulative dose using available repeated measures of blood lead to calculate an individual’s cumulative blood lead index. We review the relevance and interpretation of these lead biomarkers in the context of the toxico-kinetics of lead. In addition, we also discuss methodologic challenges that arise in studies of occupationally and environmentally exposed subjects and those concerning race/ethnicity and socioeconomic status and other important covariates

Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer

BACKGROUND: The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. METHODS: The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma) of tumor/surrounding normal tissue of esophageal cancers, using temporal temperature gradient gel electrophoresis (TTGE), followed by direct DNA sequencing to identify the mutations. RESULTS: Fourteen somatic mtDNA mutations were identified in 55% (11/20) of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively. Nine mutations (64%) were in the D-loop region. Numerous germline variations were found, at least 10 of them were novel and five were missense mutations, some of them occurred in evolutionarily conserved domains. Using real-time quantitative PCR analysis, the mtDNA content was found to increase in some tumors and decrease in others. Analysis of molecular and other clinicopathological findings does not reveal significant correlation between somatic mtDNA mutations and mtDNA content, or between mtDNA content and metastatic status. CONCLUSION: Our results demonstrate that somatic mtDNA mutations in esophageal cancers are frequent. Some missense and frameshift mutations may play an important role in the tumorigenesis of esophageal carcinoma. More extensive biochemical and molecular studies will be necessary to determine the pathological significance of these somatic mutations

Double quantum dot with integrated charge sensor based on Ge/Si heterostructure nanowires

Coupled electron spins in semiconductor double quantum dots hold promise as the basis for solid-state qubits. To date, most experiments have used III-V materials, in which coherence is limited by hyperfine interactions. Ge/Si heterostructure nanowires seem ideally suited to overcome this limitation: the predominance of spin-zero nuclei suppresses the hyperfine interaction and chemical synthesis creates a clean and defect-free system with highly controllable properties. Here we present a top gate-defined double quantum dot based on Ge/Si heterostructure nanowires with fully tunable coupling between the dots and to the leads. We also demonstrate a novel approach to charge sensing in a one-dimensional nanostructure by capacitively coupling the double dot to a single dot on an adjacent nanowire. The double quantum dot and integrated charge sensor serve as an essential building block required to form a solid-state spin qubit free of nuclear spin.Comment: Related work at http://marcuslab.harvard.edu and http://cmliris.harvard.ed