Designing Primary Prevention for People Living with HIV

Today, there are new reasons for a sharper focus on prevention for people living with HIV. Growing numbers of people with the disease are living more healthy, sexual lives. Recent evidence suggests that risk taking among both HIV-positive and negative people is increasing. After nearly two decades of life in the shadow of AIDS, communities are growing weary of traditional prevention messages and many people are openly grappling with difficult questions of intimacy and sex. Increasingly, people living with HIV also face multiple complex economic and substance abuse challenges that complicate prevention efforts.There is an urgent need -- and sufficient expertise -- to move forward with prevention campaigns focused on helping people living with HIV and AIDS avoid passing their infection along to others. Numerous innovative interventions for people with HIV show promise, including:a social marketing campaign for gay men and a five-session group intervention for women living with HIV in Massachusetts,a chat line for positives and a group session program for Latinas/Latinos in Los Angeles,Internet chat room interventions in Atlanta,a group session for gay Asian American-Pacific Islander Americans living with HIV in San Francisco, andPrevention Case Management programs newly funded by the Centers for Disease Control

An exploratory investigation of proximity control in a large-group unstructured setting

Proximity control is a common component of many classroom management strategies and has been shown to reduce disruptive behavior as well as increase academic engagement among students. Much of the research on proximity control to date has been conducted in structured classroom settings or in combination with other behavioral management techniques. This applied study investigated the effect of proximity control on student behavior in a large, unstructured setting using an ABAB withdrawal design. Results indicate that staff proximity was effective at reducing inappropriate student behavior. The study also explored the acceptability of the treatment among staff participants. Staff reported lower levels of acceptability for the implementation of proximity control compared to pretreatment methods of monitoring. A discussion of these findings and implications is included

Increasing On-Task Behavior Using Teacher Attention Delivered on a Fixed-Time Schedule

The effectiveness of fixed-time delivery of attention to increase the on-task behavior of 2 students in general education was examined. The teacher in this study provided attention to students on a 5-min fixed-time schedule and responded to students in her typical manner between cued intervals. An ABAB withdrawal design was used to test the effects of the intervention. The results of this study indicate that a fixed-time schedule of attention was effective in increasing students’ on-task behavior and decreasing their off-task behavior. Implications of the study for research and practice are discussed

Imidazolyl Alanes - Synthesis, Structures, and Reactivity Studies – Imidazolyl Alanes - Synthesis, Structures, and Reactivity Studies

Targeting the synthesis of Al/C based ambiphilic molecules, we investigated the dehydrohalogenation of a series of (benz)imidazole alane adducts. Depending on the steric bulk of the heterocycle, different dimeric products with various ring sizes were obtained. Dehydrohalogenation of the adduct of 1‐mesityl imidazole ($^{Mes}$Im) and 0.5 [tBu$_{2}$AlBr]$_{2}$ furnished the dimer 2, featuring a “classical” N‐heterocyclic carbene (NHC) and a mesoionic or “abnormal” NHC (aNHC) subunit within a single molecule. The dimer is bound loosely enough to allow thermally induced isomerization of 2 into the isomers 2$^{NHC}$ (all NHC) and 2$^{aNHC}$ (all aNHC). Dehydrohalogenation of the adduct of 1‐mesityl‐2‐methyl imidazole ($^{Mes}$Im$^{Me}$) and 0.5 [tBu$_{2}$AlBr]$_{2}$ (4) yielded the dimeric compound 5 consisting of two N‐heterocyclic olefin (NHO) subunits. Although these six‐ and eight‐membered heterocycles show no FLP‐type reactivity towards small molecules like H$_{2}$, CO or CO$_{2}$, we observed an ambiphilic behavior of the imidazolyl alanes during our studies. Salt metathesis reactions using $^{Mes}$Im resulted in the formation of 3, which can be viewed as tBu$_{2}$AlBr adduct of an Al/N ambiphile. Utilizing heterocycles such as benzimidazole or spiroindole provided the entry point to C–H (7, 9) and N–H (10) activation products, most likely resulting from a reactivity of intermediate species as Al/C ambiphiles

Breast Cancer in the Personal Genomics Era

Breast cancer is a heterogeneous disease with a complex etiology that develops from different cellular lineages, progresses along multiple molecular pathways, and demonstrates wide variability in response to treatment. The “standard of care” approach to breast cancer treatment in which all patients receive similar interventions is rapidly being replaced by personalized medicine, based on molecular characteristics of individual patients. Both inherited and somatic genomic variation is providing useful information for customizing treatment regimens for breast cancer to maximize efficacy and minimize adverse side effects. In this article, we review (1) hereditary breast cancer and current use of inherited susceptibility genes in patient management; (2) the potential of newly-identified breast cancer-susceptibility variants for improving risk assessment; (3) advantages and disadvantages of direct-to-consumer testing; (4) molecular characterization of sporadic breast cancer through immunohistochemistry and gene expression profiling and opportunities for personalized prognostics; and (5) pharmacogenomic influences on the effectiveness of current breast cancer treatments. Molecular genomics has the potential to revolutionize clinical practice and improve the lives of women with breast cancer

Leukocyte DNA as Surrogate for the Evaluation of Imprinted Loci Methylation in Mammary Tissue DNA

There is growing interest in identifying surrogate tissues to identify epimutations in cancer patients since primary target tissues are often difficult to obtain. Methylation patterns at imprinted loci are established during gametogenesis and post fertilization and their alterations have been associated with elevated risk of cancer. Methylation at several imprinted differentially methylated regions (GRB10 ICR, H19 ICR, KvDMR, SNRPN/SNURF ICR, IGF2 DMR0, and IGF2 DMR2) were analyzed in DNA from leukocytes and mammary tissue (normal, benign diseases, or malignant tumors) from 87 women with and without breast cancer (average age of cancer patients: 53; range: 31–77). Correlations between genomic variants and DNA methylation at the studied loci could not be assessed, making it impossible to exclude such effects. Methylation levels observed in leukocyte and mammary tissue DNA were close to the 50% expected for monoallellic methylation. While no correlation was observed between leukocyte and mammary tissue DNA methylation for most of the analyzed imprinted genes, Spearman's correlations were statistically significant for IGF2 DMR0 and IGF2 DMR2, although absolute methylation levels differed. Leukocyte DNA methylation levels of selected imprinted genes may therefore serve as surrogate markers of DNA methylation in cancer tissue

An investigation of matching symmetry in the human pinnae with possible implications for 3D ear recognition and sound localization

The human external ears, or pinnae, have an intriguing shape and, like most parts of the human external body, bilateral symmetry is observed between left and right. It is a well-known part of our auditory sensory system and mediates the spatial localization of incoming sounds in 3D from monaural cues due to its shape-specific filtering as well as binaural cues due to the paired bilateral locations of the left and right ears. Another less broadly appreciated aspect of the human pinna shape is its uniqueness from one individual to another, which is on the level of what is seen in fingerprints and facial features. This makes pinnae very useful in human identification, which is of great interest in biometrics and forensics. Anatomically, the type of symmetry observed is known as matching symmetry, with structures present as separate mirror copies on both sides of the body, and in this work we report the first such investigation of the human pinna in 3D. Within the framework of geometric morphometrics, we started by partitioning ear shape, represented in a spatially dense way, into patterns of symmetry and asymmetry, following a two-factor anova design. Matching symmetry was measured in all substructures of the pinna anatomy. However, substructures that stick out' such as the helix, tragus, and lobule also contained a fair degree of asymmetry. In contrast, substructures such as the conchae, antitragus, and antihelix expressed relatively stronger degrees of symmetric variation in relation to their levels of asymmetry. Insights gained from this study were injected into an accompanying identification setup exploiting matching symmetry where improved performance is demonstrated. Finally, possible implications of the results in the context of ear recognition as well as sound localization are discussed

Toward Realistic Nonstationarity of Semidiurnal Baroclinic Tides in a Hydrodynamic Model

Semidiurnal baroclinic tide sea surface height (SSH) variance and semidiurnal nonstationary variance fraction (SNVF) are compared between a hydrodynamic model and altimetry for the low‐ to middle‐latitude global ocean. Tidal frequencies are aliased by ∼10‐day altimeter sampling, which makes it impossible to unambiguously identify nonstationary tidal signals from the observations. In order to better understand altimeter sampling artifacts, the model was analyzed using its native hourly outputs and by subsampling it in the same manner as altimeters. Different estimates of the semidiurnal nonstationary and total SSH variance are obtained with the model depending on whether they are identified in the frequency domain or wave number domain and depending on the temporal sampling of the model output. Five sources of ambiguity in the interpretation of the altimetry are identified and briefly discussed. When the model and altimetry are analyzed in the same manner, they display qualitatively similar spatial patterns of semidiurnal baroclinic tides. The SNVF typically correlates above 80% at all latitudes between the different analysis methods and above 60% between the model and altimetry. The choice of analysis methodology was found to have a profound effect on estimates of the semidiurnal baroclinic SSH variance with the wave number domain methodology underestimating the semidiurnal nonstationary and total SSH variances by 68% and 66%, respectively. These results produce a SNVF estimate from altimetry that is biased low by a factor of 0.92. This bias is primarily a consequence of the ambiguity in the separation of tidal and mesoscale signals in the wave number domain.Key PointsHydrodynamic models incorporating mesoscale dynamics and tides are beginning to resolve stationary and nonstationary baroclinic tidesThe ratio of nonstationary to total semidiurnal variance computed from altimetry and HyCOM simulations agrees at low and middle latitudesComparisons of analysis methodologies show that total and nonstationary semidiurnal variances are underestimated in altimetry on averagePeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152034/1/jgrc23624_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152034/2/jgrc23624.pd

Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n = 41) and positive (n = 35) lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (P < .001, fold-change >1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis