Inference from Complex Samples

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146969/1/rssb00981.pd

The Zero-Coupon/Interest-Only Fixed-Rate Mortgage: An Alternative for Funding Low-to-Moderate Income Housing

This proposal sets forth a concept for the public/private finance of owner-occupied, single-family homes for first-time homebuyers utilizing federal guarantees and private sector mortgages. Proposed funding requires no new tax revenues. The security that the program revolves around is a Zero-coupon/Interest-only Fixed-rate mortgage (ZIF). The ZIF has the potential to improve the allocation of resources for subsidizing low-income housing, to reduce risk exposure to rapidly declining property values, and to improve the self-esteem of a group of Americans who have been depressed for far too long by making homeownership a reality.

Prenatal and Early, but Not Late, Postnatal Exposure of Mice to Sidestream Tobacco Smoke Increases Airway Hyperresponsiveness Later in Life

Background Cigarette smoke exposure in utero and during early postnatal development increases the incidence of asthma and airway hyperresponsiveness (AHR) later in life, suggesting that a possible critical period of developmental sensitivity exists in the prenatal and early postnatal periods. Objective We investigated mechanisms of susceptibility during critical developmental periods to sidestream smoke (SS) exposure and evaluated the possible effects of SS on neural responses. Methods We exposed three different age groups of mice to either SS or filtered air (FA) for 10 consecutive days beginning on gestation day (GD) 7 by maternal exposure or beginning on postnatal day (PND) 2 or PND21 by direct inhalation. Lung function, airway substance P (SP) innervation, and nerve growth factor (NGF) levels in broncho alveolar lavage fluid were measured after a single SS exposure on PND59. Results Methacholine (MCh) dose response for lung resistance (RL) was significantly elevated, and dynamic pulmonary compliance (Cdyn) was significantly decreased, in the GD7 and PND2 SS exposure groups compared with the FA groups after SS exposure on PND59. At the same time points, the percent area of SP nerve fibers in tracheal smooth muscle and the levels of NGF were significantly elevated. MCh dose–response curves for RL and Cdyn, SP nerve fiber density, and the level of NGF were not significantly changed in the PND21 exposure group after SS exposure on PND59. Conclusions These results suggest that a critical period of susceptibility to SS exposure exists in the prenatal and early postnatal period of development in mice that results in increased SP innervation, increased NGF levels in the airway, and enhanced MCh AHR later in life

Prenatal and Early, but Not Late, Postnatal Exposure of Mice to Sidestream Tobacco Smoke Increases Airway Hyperresponsiveness Later in Life

Background Cigarette smoke exposure in utero and during early postnatal development increases the incidence of asthma and airway hyperresponsiveness (AHR) later in life, suggesting that a possible critical period of developmental sensitivity exists in the prenatal and early postnatal periods. Objective We investigated mechanisms of susceptibility during critical developmental periods to sidestream smoke (SS) exposure and evaluated the possible effects of SS on neural responses. Methods We exposed three different age groups of mice to either SS or filtered air (FA) for 10 consecutive days beginning on gestation day (GD) 7 by maternal exposure or beginning on postnatal day (PND) 2 or PND21 by direct inhalation. Lung function, airway substance P (SP) innervation, and nerve growth factor (NGF) levels in broncho alveolar lavage fluid were measured after a single SS exposure on PND59. Results Methacholine (MCh) dose response for lung resistance (RL) was significantly elevated, and dynamic pulmonary compliance (Cdyn) was significantly decreased, in the GD7 and PND2 SS exposure groups compared with the FA groups after SS exposure on PND59. At the same time points, the percent area of SP nerve fibers in tracheal smooth muscle and the levels of NGF were significantly elevated. MCh dose–response curves for RL and Cdyn, SP nerve fiber density, and the level of NGF were not significantly changed in the PND21 exposure group after SS exposure on PND59. Conclusions These results suggest that a critical period of susceptibility to SS exposure exists in the prenatal and early postnatal period of development in mice that results in increased SP innervation, increased NGF levels in the airway, and enhanced MCh AHR later in life

Book reviews

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45702/1/11336_2005_Article_BF02289852.pd

Ongoing monitoring of data clustering in multicenter studies

Background: Multicenter study designs have several advantages, but the possibility of non-random measurement error resulting from procedural differences between the centers is a special concern. While it is possible to address and correct for some measurement error through statistical analysis, proactive data monitoring is essential to ensure high-quality data collection. Methods: In this article, we describe quality assurance efforts aimed at reducing the effect of measurement error in a recent follow-up of a large cluster-randomized controlled trial through periodic evaluation of intraclass correlation coefficients (ICCs) for continuous measurements. An ICC of 0 indicates the variance in the data is not due to variation between the centers, and thus the data are not clustered by center. Results: Through our review of early data downloads, we identified several outcomes (including sitting height, waist circumference, and systolic blood pressure) with higher than expected ICC values. Further investigation revealed variations in the procedures used by pediatricians to measure these outcomes. We addressed these procedural inconsistencies through written clarification of the protocol and refresher training workshops with the pediatricians. Further data monitoring at subsequent downloads showed that these efforts had a beneficial effect on data quality (sitting height ICC decreased from 0.92 to 0.03, waist circumference from 0.10 to 0.07, and systolic blood pressure from 0.16 to 0.12). Conclusions: We describe a simple but formal mechanism for identifying ongoing problems during data collection. The calculation of the ICC can easily be programmed and the mechanism has wide applicability, not just to cluster randomized controlled trials but to any study with multiple centers or with multiple observers

In Vivo Measurement of Brain GABA Concentrations by Magnetic Resonance Spectroscopy in Smelters Occupationally Exposed to Manganese

Background: Exposure to excessive manganese (Mn) levels is known to induce psychiatric and motor disorders including parkinsonian symptoms. Therefore finding a reliable means for early detection of Mn neurotoxicity is desirable. Objectives: Our goal was to study whether in-vivo brain levels of gamma-aminobutyric acid (GABA), N-acetylaspartate (NAA) and other brain metabolites in smelters were altered as a consequence of Mn exposure. Methods: T1-weighted MRI was used to visualize Mn deposition in the brain. Magnetic resonance spectroscopy (MRS) was used to quantify concentrations of NAA, glutamate and other brain metabolites in globus pallidus, putamen, thalamus, and frontal cortex from a well-established cohort of 10 male Mn-exposed smelters and 10 male age-matched control subjects. The MEGA-PRESS MRS sequence was used to determine GABA levels in a region encompassing the thalamus and adjacent parts of the basal ganglia ("GABA-VOI"). Results: Seven out of ten exposed subjects showed clear T1-hyperintense signals in the globus pallidus indicating Mn accumulation. We found a significant increase (82%; p=0.014) of GABA/tCr in the GABA-VOI of Mn-exposed subjects, as well as a distinct decrease (9%, p=0.04) of NAA/tCr in frontal cortex that strongly correlated (R= - 0.93, p<0.001) with cumulative Mn exposure. Conclusions: We demonstrated elevated GABA levels in the thalamus and adjacent basal ganglia and decreased frontal cortex NAA levels, indicating neuronal dysfunction in a brain area not primarily targeted by Mn. Therefore, the non-invasive in vivo MRS measurement of GABA and NAA may prove to be a powerful tool for detecting presymptomatic effects of Mn neurotoxicity

Lithium Therapy Improves Neurological Function and Hippocampal Dendritic Arborization in a Spinocerebellar Ataxia Type 1 Mouse Model

Huda Zoghbi and colleagues show that lithium treatment initiated before or after disease onset improves multiple symptoms of neurodegeneration in a mouse model of spinocerebellar ataxia

Tsetse salivary glycoproteins are modified with paucimannosidic N-glycans, are recognised by C-type lectins and bind to trypanosomes

African sleeping sickness is caused by Trypanosoma brucei, a parasite transmitted by the bite of a tsetse fly. Trypanosome infection induces a severe transcriptional downregulation of tsetse genes encoding for salivary proteins, which reduces its anti-hemostatic and anticlotting properties. To better understand trypanosome transmission and the possible role of glycans in insect bloodfeeding, we characterized the N-glycome of tsetse saliva glycoproteins. Tsetse salivary N-glycans were enzymatically released, tagged with either 2-aminobenzamide (2-AB) or procainamide, and analyzed by HILIC-UHPLC-FLR coupled online with positive-ion ESI-LC-MS/MS. We found that the N-glycan profiles of T. brucei-infected and naïve tsetse salivary glycoproteins are almost identical, consisting mainly (>50%) of highly processed Man3GlcNAc2 in addition to several other paucimannose, high mannose, and few hybrid-type N-glycans. In overlay assays, these sugars were differentially recognized by the mannose receptor and DC-SIGN C-type lectins. We also show that salivary glycoproteins bind strongly to the surface of transmissible metacyclic trypanosomes. We suggest that although the repertoire of tsetse salivary N-glycans does not change during a trypanosome infection, the interactions with mannosylated glycoproteins may influence parasite transmission into the vertebrate host