Spatial targeting of infectious disease control: identifying multiple, unknown sources

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Selective expression of a VHIV subfamily of immunoglobulin genes in human CD5+ B lymphocytes from cord blood.

Human B lymphocytes expressing the CD5 surface antigen (CD5+ B cells) constitute a subset capable of producing polyspecific antibodies recognizing a variety of self antigens. The repertoire of antibodies produced by CD5+ and CD5- B cells is different. However, it is not yet established whether this distribution is reflected in different immunoglobulin variable region gene (IgV) use. Rearrangement of heavy chain IgV (IgVH) genes represents one of the first identifiable stages in the maturation of B cells, and occurs in a developmentally ordered fashion. The repertoire of IgVH gene expression is highly restricted during fetal life but diversifies progressively after birth. A high frequency of VH gene use from the relatively small VHIV gene family has previously been demonstrated in human fetal liver B cells. In the present study, 102 B cell lines established by Epstein-Barr Virus-transformation of separated CD5+ and CD5- cord blood B cells, were examined for the frequency of IgV expression using monoclonal antibodies to cross-reactive idiotypes (CRI). The results demonstrate a relatively high frequency of VHIV gene use (30%) in B cells from cord blood. Furthermore, two mutually exclusive CRI associated with distinct subgroups of the VHIV family are segregated in their association with either subset of B cells. One CRI is exclusively expressed in lines established from CD5+ B cells while the other is associated with lines established from CD5- B cells

Submicron full- color LED pixels for microdisplays and micro- LED main displays

We demonstrate a bottom- up approach to the construction of micro- LEDs as small as 150 nm in lateral dimension. Molecular beam epitaxy (MBE) is used to fabricate such nanostructured LEDs from InGaN, from the blue to red regions of the spectrum, providing a single material set useful for an entire RGB display.We demonstrate a bottom- up approach to the construction of micro- LEDs as small as 150 nm in lateral dimension. Molecular beam epitaxy (MBE) is used to fabricate such nanostructured LEDs from InGaN, from the blue to red regions of the spectrum, providing a single material set useful for an entire RGB display. We then consider collective effects of arrays of such LEDs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155468/1/jsid899_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155468/2/jsid899.pd

Issues potentially affecting quality of life arising from long-term medicines use: a qualitative study

Background Polypharmacy is increasing and managing large number of medicines may create a burden for patients. Many patients have negative views of medicines and their use can adversely affect quality of life. No studies have specifically explored the impact of general long-term medicines use on quality of life. Objective To determine the issues which patients taking long-term medicines consider affect their day-to-day lives, including quality of life. Setting Four primary care general practices in North West England Methods Face-to-face interviews with adults living at home, prescribed four or more regular medicines for at least 1 year. Interviewees were identified from primary care medical records and purposively selected to ensure different types of medicines use. Interviews were recorded, transcribed and analysed thematically. Results Twenty-one interviews were conducted and analysed. Patients used an average of 7.8 medicines, 51 % were preventive, 40 % for symptom relief and 9 % treatment. Eight themes emerged: relationships with health professionals, practicalities, information, efficacy, side effects, attitudes, impact and control. Ability to discuss medicines with health professionals varied and many views were coloured by negative experiences, mainly with doctors. All interviewees had developed routines for using multiple medicines, some requiring considerable effort. Few felt able to exert control over medicines routines specified by health professionals. Over half sought additional information about medicines whereas others avoided this, trusting in doctors to guide their medicines use. Patients recognised their inability to assess efficacy for many medicines, notably those used for prophylaxis. All were concerned about possible side effects and some had poor experiences of discussing concerns with doctors. Medicines led to restrictions on social activities and personal life to the extent that, for some, life can revolve around medicines. Conclusion There is a multiplicity and complexity of issues surrounding medicines use, which impact on day-to-day lives for patients with long-term conditions. While most patients adapt to long-term medicines use, others did so at some cost to their quality of life

Effects of Visual Priming on Taste-Odor Interaction

Little is known about the influence of visual characteristics other than colour on flavor perception, and the complex interactions between more than two sensory modalities. This study focused on the effects of recognizability of visual (texture) information on flavor perception of odorized sweet beverages

Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction

We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD‐DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α‐synuclein pathology. We found moderate‐severe vascular changes and high‐vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub‐set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α‐synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging‐related neurodegenerative disorders and characterize their end‐stage clinical syndromes

Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A &lt; AV &gt; V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis

Over and Under-utilization of Cyclooxygenase-2 Selective Inhibitors by Primary Care Physicians and Specialists: The Tortoise and the Hare Revisited

To compare prescribing trends and appropriateness of use of traditional and cyclooxygenase-2 selective (COX-2) nonsteroidal anti-inflammatory drugs (NSAIDs) by primary care physicians (PCPs) and specialists. DESIGN : Retrospective cohort study. PATIENTS : One thousand five hundred and seventy-six adult patients continuously enrolled for at least 1 year with an independent practice association of a University-associated managed care plan who were started on a traditional NSAID or a COX-2 inhibitor from 1999 to 2002 and received at least 3 separate medication fills. MEASUREMENTS : Physician specialty was identified from office visits. Appropriateness of utilization was based on gastrointestinal risk characteristics. RESULTS : Primary care patients were younger and less likely to have comorbid conditions. Despite similar GI risk, COX-2 use among patients seen by PCPs was half that of patients seen by specialists (21% vs 44%, P <.001). While PCPs overused cyclooxygenase-2-specific inhibitors (COX-2s) less often than specialists (19% vs 41%, P <.001), they also tended to underuse COX-2s in patients who were at increased GI risk (46% vs 32%, P =.063). This represents a 3-fold and 8-fold difference in overuse versus underuse for PCPs and specialists, respectively. CONCLUSIONS : Using COX-2s as a model for physician adoption of new therapeutic agents, specialists were more likely to use these new medications for patients likely to benefit but were also significantly more likely to use them for patients without a clear indication. This study demonstrates the tension between appropriate adoption of innovative therapies for those individuals who would benefit from their use and those individuals who would receive no added clinical benefit but would incur added cost and be placed at increased risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75173/1/j.1525-1497.2006.00463.x.pd

Immunophenotypic studies of monoclonal gammopathy of undetermined significance

<p>Abstract</p> <p>Background</p> <p>Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell dyscrasia, comprising the most indolent form of monoclonal gammopathy. However, approximately 25% of MGUS cases ultimately progress to plasma cell myeloma (PCM) or related diseases. It is difficult to predict which subset of patients will transform. In this study, we examined the immunophenotypic differences of plasma cells in MGUS and PCM.</p> <p>Methods</p> <p>Bone marrow specimens from 32 MGUS patients and 32 PCM patients were analyzed by 4-color flow cytometry, using cluster analysis of ungated data, for the expression of several markers, including CD10, CD19, CD20, CD38, CD45, CD56 and surface and intracellular immunoglobulin light chains.</p> <p>Results</p> <p>All MGUS patients had two subpopulations of plasma cells, one with a "normal" phenotype [CD19(+), CD56(-), CD38(bright +)] and one with an aberrant phenotype [either CD19(-)/CD56(+) or CD19(-)/CD56(-)]. The normal subpopulation ranged from 4.4 to 86% (mean 27%) of total plasma cells. Only 20 of 32 PCM cases showed an identifiable normal subpopulation at significantly lower frequency [range 0–32%, mean 3.3%, p << 0.001]. The plasma cells in PCM were significantly less likely to express CD19 [1/32 (3.1%) vs. 13/29 (45%), p << 0.001] and more likely to express surface immunoglobulin [21/32 (66%) vs. 3/28 (11%), p << 0.001], compared to MGUS. Those expressing CD19 did so at a significantly lower level than in MGUS, with no overlap in mean fluorescence intensities [174 ± 25 vs. 430 ± 34, p << 0.001]. There were no significant differences in CD56 expression [23/32 (72%) vs. 18/29 (62%), p = 0.29], CD45 expression [15/32 (47%) vs. 20/30 (67%), p = 0.10] or CD38 mean fluorescence intensities [6552 ± 451 vs. 6365 ± 420, p = 0.38]. Two of the six MGUS cases (33%) with >90% CD19(-) plasma cells showed progression of disease, whereas none of the cases with >10% CD19(+) plasma cells evolved to PCM.</p> <p>Conclusion</p> <p>MGUS cases with potential for disease progression appeared to lack CD19 expression on >90% of their plasma cells, displaying an immunophenotypic profile similar to PCM plasma cells. A higher relative proportion of CD19(+) plasma cells in MGUS may be associated with a lower potential for disease progression.</p