Force fields and vibrational absorption intensities in aromatic molecules

A general quadratic force field, using the overlay technique developed by Schachtschneider and Snyder, was determined for the in-plane vibrations of Benzene and fifteen Fluorine substituted Benzenes by the cyclic refinement of the initial guesses for the forceconstants, known as the perturbation method. It was necessary to assume a Kekule type C-C/C-C interaction relation (Ri Ri+1) = -(Ri Ri+2) = (Ri Ri+3), as first introduced by Schererand Overend. Removal of this constraint gave rise to linear relationships between the force constants, and satisfactory convergence onto one force field was not obtained. The appropriate force constantsof the derived field are compared with those obtained by Duinker for the in-plane vibrations of Benzene. Although the model used is similar to his, the transferability condition is a severe extra constraint, and the extent of agreement is better than anticipated. Reassignments of the fundamentals were made for most of the molecules, and spectra were re-examined, where necessary, to obtain Raman polarisation data, and vapour phase infra red band contours.Biphenyl is known to be planar in the crystal and twisted in solution. The force field for Biphenyl and two deuterated analogues was refined to minimise Assuming that the force field does not change with geometry, the vibrational frequencies were calculated for angles of twist and an estimate obtainedfor the dihedral angle of the molecule in solution. Similar calculations were tried for difluoro Biphenyl, but asthere is insufficient frequency data available, the results were inconclusiveThe combination hands arising from the out-of-plane deformations of the C-H bonds of eight Fluorine substituted Benzenes were investigated, to measure the absolute infra red intensities, and, by a least squares analysis, to derive values for bond moments and bond moment derivatives. Regrettably, studies were limited to 1,4 difluoro Benzene, and, because of experimental difficulties, the intensities measured were so inaccurate that it was impossible to obtain reliable values for the parameters. A valuable new technique is currently being developed by other workers. In a solution spectrum, bands arising from a deformation are observed to shift in frequency, and to broaden when is added to the solution. The effects of this phenomenon were investigated for all eight molecules.<p

Transport of neutral IgG2 versus anionic IgG4 in PD : implications on the electrokinetic model

Background: It is debated whether transperitoneal membrane transport of larger (charged) molecules in peritoneal dialysis can be partially governed by the electrokinetic model. In this model, it is postulated that streaming potentials are generated across the capillary wall by forced filtration of an ionic solution, for example transcapillary ultrafiltration induced by osmotic forces as in peritoneal dialysis. We investigated the presence of streaming potentials in the process of transperitoneal transport in Peritoneal Dialysis (PD) patients by measuring ratios of dialysate concentrations of IgG2 (neutral) and IgG4 (negative), both 150kD, under different conditions of transcapillary ultrafiltration. Methods: Adult PD patients randomly got two consecutive dwells of 120 min each, with either 2 L Physioneal 1.36% or 3.86% glucose dialysis fluid (Baxter, USA) as their first dwell. A blood sample was taken at the test start, and dialysate samples were taken at 5, 15, 30, 60 and 120 min. IgG2 and IgG4 concentrations were measured (ELISA) and ratios calculated. Results: In 10 patients (65 +/- 17 years, 2017 months on dialysis), drained volume after 120 min was different between the 1.36% (1950 [1910; 2020] mL) and 3.86% (2540 [2380; 2800] mL) glucose dwells (P = 0.007). At none of the time points and irrespective of glucose concentration, a significant difference was found between the IgG2/IgG4 ratios at any time point. Conclusion: Our data failed to demonstrate a difference in the transport ratios of two macromolecules with same molecular weight but different charge, as would be expected by the electrokinetic model, and this despite sufficient differences in transcapillary ultrafiltration

Antibody targeting of B7-H4 enhances the immune response in urothelial carcinoma.

Patients with locally advanced and metastatic urothelial carcinoma have a low survival rate (median 15.7 months, 13.1-17.8), with only a 23% response rate to monotherapy treatment with anti-PDL1 checkpoint immunotherapy. To identify new therapeutic targets, we profiled the immune regulatory signatures during murine cancer development using the BBN carcinogen and identified an increase in the expression of the T cell inhibitory protein B7-H4 (VTCN1, B7S1, B7X). B7-H4 expression temporally correlated with decreased lymphocyte infiltration. While the increase in B7-H4 expression within the bladder by CD11

Importance of reconnection with ICU survivors to ICU recovery program clinicians

No abstract available

Amicus Brief, Lebron v. Gottlieb Memorial Hospital

Illinois Public Act 82-280, § 2-1706.5, as amended by P.A. 94-677, § 330 (eff. Aug. 25, 2005), and as codified as 735 ILCS 5/2-1706.5(a), imposes a $500,000 “cap” on the noneconomic damages that may be awarded in a medical malpractice suit against a physician or other health care professional, and a$1 million “cap” on the noneconomic damages that may be awarded against a hospital, its affiliates, or their employees. This brief will address two of the questions presented for review by the parties: 1. Does the cap violate the Illinois Constitution’s prohibition on “special legislation,” Art. IV, § 3, because it unnecessarily, arbitrarily, and irrationally grants exceptional benefits and privileges exclusively to certain classes of tort defendants. 2. Does the cap violate the Illinois Constitution’s guarantee of “equal protection,” Art. I, § 2, because it unnecessarily, arbitrarily, and irrationally imposes extraordinary burdens uniquely upon certain classes and sub-classes of tort plaintiffs

Reported frequency of physical activity in a large epidemiological study: relationship to specific activities and repeatability over time

<p>Abstract</p> <p>Background</p> <p>How overall physical activity relates to specific activities and how reported activity changes over time may influence interpretation of observed associations between physical activity and health. We examine the relationships between various physical activities self-reported at different times in a large cohort study of middle-aged UK women.</p> <p>Methods</p> <p>At recruitment, Million Women Study participants completed a baseline questionnaire including questions on frequency of strenuous and of any physical activity. About 3 years later 589,896 women also completed a follow-up questionnaire reporting the hours they spent on a range of specific activities. Time spent on each activity was used to estimate the associated excess metabolic equivalent hours (MET-hours) and this value was compared across categories of physical activity reported at recruitment. Additionally, 18,655 women completed the baseline questionnaire twice, at intervals of up to 4 years; repeatability over time was assessed using the weighted kappa coefficient (κ_weighted) and absolute percentage agreement.</p> <p>Results</p> <p>The average number of hours per week women reported doing specific activities was 14.0 for housework, 4.5 for walking, 3.0 for gardening, 0.2 for cycling, and 1.4 for all strenuous activity. Time spent and the estimated excess MET-hours associated with each activity increased with increasing frequency of any or strenuous physical activity reported at baseline (tests for trend, P < 0.003), although the associations for housework were by far the weakest (Spearman correlations, 0.01 and -0.03 respectively for housework, and 0.11-0.37 for all other activities). Repeatability of responses to physical activity questions on the baseline questionnaire declined significantly over time. For strenuous activity, absolute agreement was 64% (κ_weighted= 0.71) for questionnaires administered less than 6 months apart, and 52% (κ_weighted= 0.51) for questionnaires more than 2 years apart. Corresponding values for any physical activity were 57% (κ_weighted= 0.67) and 47% (κ_weighted= 0.58).</p> <p>Conclusions</p> <p>In this cohort, responses to simple questions on the frequency of any physical activity and of strenuous activity asked at baseline were associated with hours spent on specific activities and the associated estimated excess MET-hours expended, reported 3 years later. The weakest associations were with housework. Agreement for identical questions asked on two occasions about the frequency of physical activity decreased over time.</p

Does information from ClinicalTrials.gov increase transparency and reduce bias? Results from a five-report case series

Background We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. Method We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review’s last literature search, screened the records using the review’s eligibility criteria, extracted information, and assessed risk of bias and applicability. Each team then evaluated the impact of the evidence found in ClinicalTrials.gov on the conclusions in the review. Results Across the five reviews, the number of studies that had both a registry record and a publication varied widely, from none in one review to 43% of all studies identified in another. Among the studies with both a record and publication, there was also wide variability in the match between published outcomes and those listed in ClinicalTrials.gov. Of the 173 total ClinicalTrials.gov records identified across the five projects, between 11 and 43% did not have an associated publication. In the 14% of records that contained results, the new data provided in the ClinicalTrials.gov records did not change the results or conclusions of the reviews. Finally, a large number of published studies were not registered in ClinicalTrials.gov, but many of these were published before ClinicalTrials.gov’s inception date of 2000. Conclusion Improved prospective registration of trials and consistent reporting of results in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in finding unpublished information and identifying potential biases. In addition, consistent indexing in databases, such as MEDLINE, would allow for better matching of records and publications, leading to increased utility of these searches for systematic review projects

Lithospheric geometry of the Wopmay orogen from a Slave craton to Bear Province magnetotelluric transect

Two‐dimensional inversions of lithospheric‐probing magnetotelluric (MT) data at a total of 20 sites acquired along an approximately east–west 300‐km‐long profile across the Wopmay orogen in the Northwest Territories, Canada, provide electrical resistivity models of the boundary between the Archean Slave craton and the adjacent Proterozoic Bear Province. An analysis of distortion effects and structural dimensionality indicates that the MT responses are primarily one‐dimensional or only weakly two‐dimensional with a depth‐independent geoelectric strike angle of N32°E, consistent with regional structural geology. The regional‐scale model, generated from the longer period responses from all of the sites along the profile, reveals significant lateral variations in the lithospheric mantle. Resistive cratonic roots are imaged to depths of ∼200 km beneath both the Slave craton and the Hottah terrane of the Bear Province. These are separated by a less resistive region beneath the Great Bear magmatic zone, which is speculatively interpreted as a consequence of a decrease in the grain size of olivine in the Wopmay mantle, caused by localized shearing, compared to its neighboring cratonic roots. Focused two‐dimensional models, from higher frequency responses at sites on specific sections of the profile, reveal the resistivity structure at crustal depths beneath the region. These suggest that the root of the Slave craton crosses beneath the Wopmay orogen, and that the Wopmay fault zone does not penetrate into the lower crust. A comparison of these results with those obtained during the Lithoprobe project farther south shows striking along strike variations in the conductivity structure associated with the Wopmay orogen

Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials

The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals. The majority of viruses identified were clade B and C; with clades A, D, F and G and recombinants AC and BF detected at lower frequencies. We tested eight bnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10–1074 and 10E8v4) for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998–2010), the HVTN703/HPTN081 clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best against clade C viruses and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. Overall, the AMP placebo viruses represent a valuable resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs and highlight the need to update reference panels regularly. Our data also suggests that combining bnAbs in passive immunization trials would improve coverage of global viruses

Neutralization profiles of HIV-1 viruses from the VRC01 Antibody Mediated Prevention (AMP) trials.

The VRC01 Antibody Mediated Prevention (AMP) efficacy trials conducted between 2016 and 2020 showed for the first time that passively administered broadly neutralizing antibodies (bnAbs) could prevent HIV-1 acquisition against bnAb-sensitive viruses. HIV-1 viruses isolated from AMP participants who acquired infection during the study in the sub-Saharan African (HVTN 703/HPTN 081) and the Americas/European (HVTN 704/HPTN 085) trials represent a panel of currently circulating strains of HIV-1 and offer a unique opportunity to investigate the sensitivity of the virus to broadly neutralizing antibodies (bnAbs) being considered for clinical development. Pseudoviruses were constructed using envelope sequences from 218 individuals. The majority of viruses identified were clade B and C; with clades A, D, F and G and recombinants AC and BF detected at lower frequencies. We tested eight bnAbs in clinical development (VRC01, VRC07-523LS, 3BNC117, CAP256.25, PGDM1400, PGT121, 10-1074 and 10E8v4) for neutralization against all AMP placebo viruses (n = 76). Compared to older clade C viruses (1998-2010), the HVTN703/HPTN081 clade C viruses showed increased resistance to VRC07-523LS and CAP256.25. At a concentration of 1μg/ml (IC80), predictive modeling identified the triple combination of V3/V2-glycan/CD4bs-targeting bnAbs (10-1074/PGDM1400/VRC07-523LS) as the best against clade C viruses and a combination of MPER/V3/CD4bs-targeting bnAbs (10E8v4/10-1074/VRC07-523LS) as the best against clade B viruses, due to low coverage of V2-glycan directed bnAbs against clade B viruses. Overall, the AMP placebo viruses represent a valuable resource for defining the sensitivity of contemporaneous circulating viral strains to bnAbs and highlight the need to update reference panels regularly. Our data also suggests that combining bnAbs in passive immunization trials would improve coverage of global viruses