A Reading of Johnny Faustus

Flyer for Fall 1997 ICS Faculty Fellow Lecture by F. Scott Regan.https://scholarworks.bgsu.edu/ics_fellow_lectures/1026/thumbnail.jp

Tonack v. Montana Bank: Preemption, Interpretation, and Older Employees Under Montana\u27s Wrongful Discharge from Employment Act

Tonack v. Montana Bank: Preemption, Interpretation, and Older Employees Under Montana\u27s Wrongful Discharge from Employment Ac

Electron tomography at 2.4 {\AA} resolution

Transmission electron microscopy (TEM) is a powerful imaging tool that has found broad application in materials science, nanoscience and biology(1-3). With the introduction of aberration-corrected electron lenses, both the spatial resolution and image quality in TEM have been significantly improved(4,5) and resolution below 0.5 {\AA} has been demonstrated(6). To reveal the 3D structure of thin samples, electron tomography is the method of choice(7-11), with resolutions of ~1 nm^3 currently achievable(10,11). Recently, discrete tomography has been used to generate a 3D atomic reconstruction of a silver nanoparticle 2-3 nm in diameter(12), but this statistical method assumes prior knowledge of the particle's lattice structure and requires that the atoms fit rigidly on that lattice. Here we report the experimental demonstration of a general electron tomography method that achieves atomic scale resolution without initial assumptions about the sample structure. By combining a novel projection alignment and tomographic reconstruction method with scanning transmission electron microscopy, we have determined the 3D structure of a ~10 nm gold nanoparticle at 2.4 {\AA} resolution. While we cannot definitively locate all of the atoms inside the nanoparticle, individual atoms are observed in some regions of the particle and several grains are identified at three dimensions. The 3D surface morphology and internal lattice structure revealed are consistent with a distorted icosahedral multiply-twinned particle. We anticipate that this general method can be applied not only to determine the 3D structure of nanomaterials at atomic scale resolution(13-15), but also to improve the spatial resolution and image quality in other tomography fields(7,9,16-20).Comment: 27 pages, 17 figure

Contemporary NSTEMI management: the role of the hospitalist.

Non-ST-segment elevation myocardial infarction (NSTEMI) is defined as elevated cardiac biomarkers of necrosis in the absence of persistent ST-segment elevation in the setting of anginal symptoms or other acute event. It carries a poorer prognosis than most ST-segment elevation events, owing to the typical comorbidity burden of the older NSTEMI patients as well as diverse etiologies that add complexity to therapeutic decision-making. It may result from an acute atherothrombotic event (\u27Type 1\u27) or as the result of other causes of mismatch of myocardial oxygen supply and demand (\u27Type 2\u27). Regardless of type and other clinical factors, the hospital medicine specialist is increasingly responsible for managing or coordinating the care of these patients. Following published guidelines for risk stratification and basing anti-anginal, anticoagulant, antiplatelet, other pharmacologic therapies, and overall management approach on that individualized patient risk assessment can be expected to result in better short- and long-term clinical outcomes, including near-term readmission and recurrent events. We present here a review of the evidence basis and expert commentary to assist the hospitalist in achieving those improved outcomes in NSTEMI. Given that the Society for Hospital Medicine cites care of patients with acute coronary syndrome as a core competency for hospitalists, it is essential that those specialists stay current on optimal NSTEMI care

Exploring how age influences sensory perception, thirst and hunger during the consumption of oral nutritional supplements using the check-all-that-apply methodology

The Check-all-that-apply (CATA) method has been widely used for the sensory characterisation of many different foods and beverages. However, this methodology has been rarely used with older adults. The aim of this study was to measure the effectiveness of the CATA methodology to investigate the differences in sensory perception of Oral Nutritional Supplements (ONS) between younger and community dwelling older adults over successive sips of a full volume of two ONS. The study also sought to measure the effects of ONS on thirst, hunger and fullness. 160 participants (eighty aged over 65 and eighty aged 18-35) evaluated two ONS over two different days. They consumed five 40 ml aliquots of ONS amounting to one serving. After each 40 ml they completed a CATA questionnaire, which recorded liking using a 9-point hedonic scale and hunger, fullness, desire, and thirst using 100 mm visual analogue scales. The results indicated significantly lower levels in hunger (p ≤ 0.01) and thirst (p ≤ 0.01) in the older cohort than the younger cohort. Significant differences in texture perception with age were also observed with the younger cohort selecting ‘Watery’ significantly more (p ≤ 0.05) than the older cohort for ONS 1 and ‘Thick’ and ‘Viscous’ significantly more (p ≤ 0.05) for ONS 2. The study showed that the CATA methodology is appropriate for use with older adults. The findings enhanced our understanding of how an older population experience ONS and drivers of ‘liking’. This information has the potential to enhance ONS adherence and ultimately improve the nutritional status of older people

Capacity limitations of visual memory in two-interval comparison of Gabor arrays

The capacity of short-term visual memory (VSTM) was assessed in a two-interval spatial frequency (SF) discrimination task. The cued Gabor target in a multi-element array either increased or decreased in SF across a 2s interstimulus interval (ISI). Distracters as well as target were made to change across ISI so that memory of the individual SF of Gabor elements was required to solve the discrimination. The dynamics of the information loss from visual memory were analysed by manipulating the timing of spatial cues and masks. Cueing the target position before the first display gave thresholds comparable with those for a single Gabor patch. Cues placed after the first display gave higher thresholds indicating some loss of information. Within the ISI there was little increase in threshold or set size effect with cue delay. However there was a sharp rise in thresholds for cue positions after the second display. Gabor masks placed before a mid-ISI cue were more effective than noise masks or Gabor masks placed after the cue. With a cue placed late in the ISI, preceded by a Gabor mask, the masking effect decreased with increasing delay of the mask after the first display. This suggests a selective, dynamic but increasingly durable representation of the initial stimulus is built up in memory, and there is a graded form of “overwriting” of this representation by new stimuli

Banner News

https://openspace.dmacc.edu/banner_news/1293/thumbnail.jp

The "ART" of Linkage: Pre-Treatment Loss to Care after HIV Diagnosis at Two PEPFAR Sites in Durban, South Africa

BACKGROUND. Although loss to follow-up after antiretroviral therapy (ART) initiation is increasingly recognized, little is known about pre-treatment losses to care (PTLC) after an initial positive HIV test. Our objective was to determine PTLC in newly identified HIV-infected individuals in South Africa. METHODOLOGY/PRINCIPAL FINDINGS. We assembled the South African Test, Identify and Link (STIAL) Cohort of persons presenting for HIV testing at two sites offering HIV and CD4 count testing and HIV care in Durban, South Africa. We defined PTLC as failure to have a CD4 count within 8 weeks of HIV diagnosis. We performed multivariate analysis to identify factors associated with PTLC. From November 2006 to May 2007, of 712 persons who underwent HIV testing and received their test result, 454 (64%) were HIV-positive. Of those, 206 (45%) had PTLC. Infected patients were significantly more likely to have PTLC if they lived =10 kilometers from the testing center (RR=1.37; 95% CI: 1.11-1.71), had a history of tuberculosis treatment (RR=1.26; 95% CI: 1.00-1.58), or were referred for testing by a health care provider rather than self-referred (RR=1.61; 95% CI: 1.22-2.13). Patients with one, two or three of these risks for PTLC were 1.88, 2.50 and 3.84 times more likely to have PTLC compared to those with no risk factors. CONCLUSIONS/SIGNIFICANCE. Nearly half of HIV-infected persons at two high prevalence sites in Durban, South Africa, failed to have CD4 counts following HIV diagnosis. These high rates of pre-treatment loss to care highlight the urgent need to improve rates of linkage to HIV care after an initial positive HIV test.US National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476, K23 AI068458); the Harvard University Center for AIDS Research (P30 AI42851); National Institutes of Health (K24 AR 02123); the Doris Duke Charitable Foundation (Clinical Scientist Development Award); the Harvard University Program on AID

Wilms’ tumour antigen 1 Immunity via DNA fusion gene vaccination in haematological malignancies by intramuscular injection followed by intramuscular electroporation: a Phase II non-randomised clinical trial (WIN)

Background: In the UK almost 7000 people are diagnosed with leukaemia each year, but despite continuing advances in diagnosis and treatment with new drugs, such as the tyrosine kinase inhibitors, the majority of these patients will eventually die from their disease. Until quite recently, the only treatment to offer the possibility of long-term disease-free survival was allogeneic stem cell transplantation. However, this carries a substantial risk of mortality and is available to only a minority of patients.Objectives: The aim of the study was to test the hypothesis that molecular and clinical responses, induced by T lymphocytes (T cells), can be predicted by increases in the number of CD8+ (cluster of differentiation 8-positive) T cells specific for the vaccine-encoded T-cell epitopes. This project also aimed to build on the established programme of deoxyribonucleic acid (DNA) fusion-gene vaccination delivered by intramuscular injection, exploiting a unique experience with electroporation, to induce durable immune responses with the aim of controlling disease by precision attack of the tumour by CD8+ T cells.Method: A non-randomised, open-label, single-dose-level Phase II clinical trial in two patient groups [chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML)] on stable doses of imatinib. Human leucocyte antigen A2-positive (HLA A2+) patients were vaccinated with two DNA vaccines: (1) p.DOM–WT1-37 (epitope sequence: VLDFAPPGA); and (2) p.DOM–WT1-126 (epitope sequence: RMFPNAPYL). The HLA A2-negative patients formed an unvaccinated control group. The sample size for the HLA A2+ group was originally determined following Simon’s optimal Phase II trial design (Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1–10). This was changed to A’Hern’s single-stage design during the course of the trial (A’Hern RP. Sample size tables for single-stage phase II designs. Stat Med 2001;20:859–66), which was endorsed by the trial’s independent oversight committees.Results: The study included 12 patients with CML who were vaccinated and nine patients with CML who were unvaccinated as the control group. Both the vaccines and the electroporation were safe, with no new or unexpected toxicities. The evaluation adverse events of special interest (heart, bone marrow, renal) did not reveal safety concerns. Two BCR–ABL (breakpoint cluster region–Abelson murine leukaemia viral oncogene homolog 1) responses were observed, both of which were defined as a major response, with one in each group. Two Wilms’ tumour antigen 1 (WT1) molecular responses were observed in the vaccinated group and one was observed in the control group. At an immunological level, the vaccine performed as expected.Conclusions: The study met its primary decision-making target with one major molecular response in BCR–ABL transcript levels. Overall, the data showed, in this clinical setting, the immunogenicity and safety of the vaccine.Limitations: The study did not complete recruitment and there were multiple hurdles that contributed to this failure. This is disappointing given the robust induction immune responses against WT1 T-cell responses in 7 out of 10 evaluable patients.Future work: Evaluation of the p.DOM–WT1 vaccines in AML remains attractive clinically, but it is unlikely to be feasible at this time. Combination of the DNA vaccine approach with strategies to expand T-cell responses with immunomodulatory antibodies is in development.Funding details: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership, and Bloodwise