Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 94
Filter
1.
Article in English | MEDLINE | ID: mdl-39225808

ABSTRACT

BACKGROUND: Injured patients have high rates of uninsurance, which is associated with worse outcomes. Insurance linkage programs that connect patients to Medicaid coverage can prevent catastrophic costs for patients. Less is known about the long-term impact of insurance enrollment. We examined health care utilization for previously uninsured patients, hypothesizing that newly insured patients postinjury would use health care more than those remaining uninsured. METHODS: We linked institutional trauma registry data to the electronic medical record to identify injured patients aged 18 to 64 years from 2017 to 2021. Patients admitted without insurance and then retroactively insured (RI) during hospitalization were compared with patients with preestablished Medicaid (Medicaid insured [MI]) and those remaining uninsured. We compared demographic and injury characteristics and future health care utilization, including hospitalizations, emergency department (ED) visits, and clinic visits, among groups at 30 days and 12 months postinjury. Patient-reported outcomes (PROs) 6 months after injury were compared by group for a subset of patients participating in an ongoing study of long-term PROs. RESULTS: We compared 494 RI patients with 1,706 MI and 148 uninsured patients. Retroactively insured patients were younger, more likely to have penetrating injuries, and longer hospitalization than other groups. There was a significant increase in ED and clinic visits and hospital admissions at 30 days and 12 months between RI and uninsured patients (p < 0.001). Using multivariable logistic regression, RI was associated with higher future ED utilization, hospital admissions, and specialist visits at 30 days and 12 months compared with uninsured patients. Of the 265 patients with 6-month PROs, Medicaid coverage was not associated with any significant difference in physical function or anxiety. CONCLUSION: Patients enrolled in insurance postinjury are more likely to use health care in the future than patients without insurance, but the downstream effects are less clear. Health insurance is a necessary step but not independently sufficient to optimize care and improve health outcomes. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

2.
J Phys Chem A ; 128(34): 7137-7144, 2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39150465

ABSTRACT

We report the infrared photodissociation spectrum of tagged protonated valine in the range 1000-1900 cm-1, prepared in a cryogenic ion trap. Comparison of experimental results with calculated infrared spectra based on density functional theory shows that the hydroxyl group of the carboxylic acid functionality and the protonated amine group adopt a trans configuration. Nitrogen and methane molecules were used as messenger tags with optimal tagging temperatures of 30 K for N2 and 60 K for CH4. While the calculated infrared spectra of the tagged ion suggest only a weak influence of the messenger tag on the frequency positions of ValH+, the measured intensities for N2-tagged ValH+ appear strongly suppressed for all but the highest frequency feature at 1773 cm-1. We trace this behavior to the binding energy of the N2 tag, which is significantly higher than that of CH4, based on density functional and coupled cluster calculations and rate estimates for photoinduced unimolecular dissociation from statistical theory.

3.
J Trauma Acute Care Surg ; 97(2S Suppl 1): S14-S18, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38750632

ABSTRACT

BACKGROUND: Top-tier general and specialty scientific journals serve as a bellwether for national research priorities. We hypothesize that military-relevant publications are underrepresented in the scientific literature and that such publications decrease significantly during peacetime. METHODS: We identified high impact journals in the fields of Medicine, Surgery and Critical Care and developed Boolean searches for military-focused topics using National Library of Medicine Subject Headings terms. A PubMed search from 1950 to 2020 returned the number of research publications in relevant journals and the rate of military-focused publications by year. Rates of military publications were compared between peacetime and wartime. Publication rate trends were modeled with a quadratic function controlling for the start of active conflict and total casualty numbers. Baseline proportions of military physicians relative to the civilian sector served to estimate expected publication rates. Comparisons were performed using Pearson's χ 2 and Mann-Whitney U test, with p < 0.05 considered a significant difference. RESULTS: From 1950 to 2020, a total of 716,340 manuscripts were published in the journals queried. Of these, military-relevant manuscripts totaled 4,052 (0.57%). We found a significant difference in the rate of publication during times of peace and times of war (0.40% vs. 0.69%, p < 0.001). Subgroup analysis found significantly reduced rates of publication in medical and critical care journals during peacetime. For each conflict, the percentage of military-focused publications peaked during periods of war but then receded below baseline levels within a median of 2.5 years (interquartile range, 1.5-3.8 years) during peacetime. The proportion of military-focused publications never reached the current proportion of military physicians in the workforce. CONCLUSION: There is marked reduction in rates of publication for military-focused articles in high impact journals during peacetime. Military-focused articles are underrepresented in high-impact journals. Investigators of military-relevant topics and editors of high-impact journals should seek to close this gap.


Subject(s)
Bibliometrics , Biomedical Research , Military Medicine , Military Medicine/statistics & numerical data , Humans , Biomedical Research/statistics & numerical data , Periodicals as Topic/statistics & numerical data , United States
4.
Anal Chem ; 96(22): 8875-8879, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38776223

ABSTRACT

This work presents a benchtop method for collecting the room temperature gas phase infrared (IR) action spectra of protonated amino acids and their isomers. The adopted setup uses a minimally modified commercial electrospray ionization linear ion trap mass spectrometer (ESI-LIT-MS) coupled to a broadband continuous wave (cw) quantum cascade laser (QCL) source. This approach leverages messenger assisted action spectroscopic techniques using water-tagged molecular ions with complex formation, irradiation, and subsequent analysis, all taking place within a single linear ion trap stage. This configuration thus circumvents the use of multiple mass selection and analysis stages, cryogenic buffer cells, and complex high-power laser systems typically called upon to execute these techniques. The benchtop action spectrometer is used to collect the 935-1600 cm-1 (6.2-10.7 µm) IR action spectrum of a collection of amino acids and a dipeptide with results cross referenced against literature examples obtained with a free electron laser source. Recorded IR spectra are used for the analysis of binary mixture samples composed of constitutional isomers α-alanine and ß-alanine with ratios determined to ∼4% measurement uncertainty without the aid of a front-end separation stage. This turn-key QCL-based approach is a major step in showing the viability of tag-based action spectroscopic techniques for use in future in situ planetary science sensors and general analytical applications.

5.
J Small Anim Pract ; 65(2): 132-143, 2024 02.
Article in English | MEDLINE | ID: mdl-37956993

ABSTRACT

OBJECTIVES: Tick-borne encephalitis virus and louping ill virus are neurotropic flaviviruses transmitted by ticks. Epidemiologically, tick-borne encephalitis is endemic in Europe whereas louping ill's predominant geographical distribution is the UK. Rarely, these flaviviruses affect dogs causing neurological signs. This case series aimed to describe the clinical, clinicopathological, and imaging findings, as well as the outcomes in six dogs with meningoencephalitis and/or meningomyelitis caused by a flavivirus in the UK in 2021. MATERIALS AND METHODS: Observational retrospective case-series study. Clinical data were retrieved from medical records of dogs with positive serological or immunohistochemical results from three different institutions from spring to winter 2021. RESULTS: Six dogs were included in the study. All dogs presented an initial phase of pyrexia and/or lethargy followed by progressive signs of spinal cord and/or intracranial disease. Magnetic resonance imaging showed bilateral and symmetrical lesions affecting the grey matter of the thalamus, pons, medulla oblongata, and thoracic or lumbar intumescences with none or mild parenchymal and meningeal contrast enhancement. Serology for tick-borne encephalitis virus was positive in five dogs with the presence of seroconversion in two dogs. The viral distinction between flaviviruses was not achieved. One dog with negative serology presented positive immunohistochemistry at post-mortem examination. Three dogs survived but presented neurological sequelae. Three dogs were euthanased due to the rapid progression of the clinical signs or static neurological signs. CLINICAL SIGNIFICANCE: These cases raise awareness of the presence of tick-borne encephalitis as an emergent disease or the increased prevalence of louping ill virus affecting dogs in the UK.


Subject(s)
Dog Diseases , Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne , Ticks , Dogs , Animals , Encephalitis, Tick-Borne/diagnosis , Encephalitis, Tick-Borne/epidemiology , Encephalitis, Tick-Borne/veterinary , Retrospective Studies , United Kingdom/epidemiology , Dog Diseases/diagnosis
6.
Adv Sci (Weinh) ; 9(27): e2201227, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35821385

ABSTRACT

A broadband, high efficiency polarized beam splitter (PBS) metagrating based on integrated resonant units (IRUs) to enable simultaneous polarization analysis, spectral dispersion, and spatial imaging in the near infrared (NIR) is developed. A PBS metagrating with a diameter of 60 mm is the key technology component of the high-resolution multiple-species atmospheric profiler in the NIR (HiMAP-NIR), which is a spaceborne instrument concept crafted to be a core payload of NASA's new generation Earth System Observatory. HiMAP-NIR will enable the aerosol profiling in Earth's planetary boundary layer (from surface to2 km altitude) by simultaneously measuring four spatial-spectral-polarimetric images from 680 to 780 nm. Through detailed optimization of hybridized resonant modes in IRUs, the PBS metagrating shows a diffraction efficiency of 70% (or better) for all four linear-polarized incident light, and polarization contrasts between orthogonal states are 0.996 (or better) from 680 to 780 nm. It meets the stringent performance required by the HiMAP-NIR exploiting a new paradigm for the broad applications of metasurfaces.

7.
Rev Sci Instrum ; 89(7): 073109, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30068109

ABSTRACT

We present a system level description of a cavity-enhanced millimeter-wave spectrometer that is the first in its class to combine source and detection electronics constructed from architectures commonly deployed in the mobile phone industry and traditional pulsed Fourier transform techniques to realize a compact device capable of sensitive and specific in situ gas detections. The instrument, which has an operational bandwidth of 90-102 GHz, employs several unique components, including a custom-designed pair of millimeter-wave transmitter and heterodyne receiver integrated circuit chips constructed with 65 nm complementary metal-oxide semiconductor (CMOS) techniques. These elements are directly mated to a hybrid coupling structure that enables free-space interaction of the electronics with a small gas volume while also acting as a cavity end mirror. Instrument performance for sensing of volatile compounds is highlighted with experimental trials taken in bulk gas flows and seeded molecular beam environments.

8.
J Thorac Dis ; 9(Suppl 2): S122-S129, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28446975

ABSTRACT

The use of liquid nitrogen to treat skin and mucosal lesions is well understood in the dermatologic and gastrointestinal literature. Direct spray cryotherapy (SCT) in the airway has shown promising results in the treatment of esophageal premalignant and even invasive lesions. In the airway, several studies have shown it to be a safe, effective treatment for both benign and malignant disease. It is easily administered in the outpatient setting and can be repeated several times without undue side effects. In this article, we review the current literature on the use of SCT for the treatment of endobronchial lesions and also describe our own institutional experience of the use of SCT in the airway. The use of proper technique and airway venting is important in mitigating the complications of barotrauma from massive expansion of nitrogen upon conversion from the liquid to gaseous state. We also review some of the basic science principals behind the use of the cryotherapy to treat lesions in different tissues. We feel that SCT is a potential area for further research at both clinical and basic science level.

9.
J Chem Phys ; 145(20): 204303, 2016 Nov 28.
Article in English | MEDLINE | ID: mdl-27908108

ABSTRACT

The near-ultraviolet π*←π absorption system of weakly bound complexes formed between tropolone (TrOH) and formic acid (FA) under cryogenic free-jet expansion conditions has been interrogated by exploiting a variety of fluorescence-based laser-spectroscopic probes, with synergistic quantum-chemical calculations built upon diverse model chemistries being enlisted to unravel the structural and dynamical properties of the pertinent ground [X̃1A'] and excited [Ã1A'π*π] electronic states. For binary TrOH ⋅ FA adducts, the presence of dual hydrogen-bond linkages gives rise to three low-lying isomers designated (in relative energy order) as INT, EXT1, and EXT2 depending on whether docking of the FA ligand to the TrOH substrate takes place internal or external to the five-membered reaction cleft of tropolone. While the symmetric double-minimum topography predicted for the INT potential surface mediates an intermolecular double proton-transfer event, the EXT1 and EXT2 structures are interconverted by an asymmetric single proton-transfer process that is TrOH-centric in nature. The Ã-X̃ origin of TrOH ⋅ FA at ν̃00=27 484.45cm-1 is displaced by δν̃00=+466.76cm-1 with respect to the analogous feature for bare tropolone and displays a hybrid type - a/b rotational contour that reflects the configuration of binding. A comprehensive analysis of vibrational landscapes supported by the optically connected X̃1A' and Ã1A'π*π manifolds, including the characteristic isotopic shifts incurred by partial deuteration of the labile TrOH and FA protons, has been performed leading to the uniform assignment of numerous intermolecular (viz., modulating hydrogen-bond linkages) and intramolecular (viz., localized on monomer subunits) degrees of freedom. The holistic interpretation of all experimental and computational findings affords compelling evidence that an external-binding motif (attributed to EXT1), rather than the thermodynamically more stable cleft-bound (INT) form, was the carrier of fluorescence signals observed during the present work.

10.
Appl Environ Microbiol ; 80(23): 7388-97, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25239906

ABSTRACT

The objective of this study was to systematically assess the bifidogenic effect of three commonly used prebiotic products using in vitro cultures of infant fecal samples. Fresh stool samples collected from six term infants, each exclusively fed human milk (n = 3) or infant formula (n = 3), at 28 days of age were used as inocula. The following prebiotic products were added at concentrations applicable to infant formula: Vivinal GOS 15 (containing 28.5% galacto-oligosaccharide [GOS]) at 7.2 g/liter, Beneo HP (99.5% long-chain inulin [IN]) at 0.8 g/liter, Beneo Synergy 1 (enriched oligofructose and inulin [OF-IN]) at 4 g/liter, and a combination of Vivinal GOS 15 (7.2 g/liter) and Beneo HP (0.8 g/liter) (GOS-IN). The growth of total bacteria, Bifidobacterium, Bacteroides, Bifidobacterium longum, and Escherichia coli was quantified using specific quantitative PCR (qPCR). Bifidobacterium was also enumerated on selective Beerens agar plates, with representative colonies identified by sequencing of their 16S rRNA genes. Volatile fatty acids (VFA) and pH in the cultures were also determined. Irrespective of the feeding methods, the GOS product, either alone or in combination with Beneo HP, resulted in substantially higher growth of total bifidobacteria, and much of this growth was attributed to growth of B. longum. Beneo Synergy 1 also increased the abundance of total bifidobacteria and B. longum. Corresponding to the increases in these two bacterial groups, acetic acid concentrations were higher, while there was a trend of lower E. coli levels and pH. The lower pH and higher acetic acid concentration might be directly responsible for the lower E. coli population. At the concentrations studied, the GOS product was more bifidogenic and potent in inhibiting E. coli than the other products tested. These results suggest that supplementation of infant formula with GOS may increase intestinal bifidobacteria and benefit infant health.


Subject(s)
Feces/microbiology , Gastrointestinal Microbiome/drug effects , Microbiota/drug effects , Oligosaccharides/metabolism , Prebiotics/administration & dosage , Bacterial Load , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Fatty Acids/analysis , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Infant , RNA, Ribosomal, 16S/genetics , Real-Time Polymerase Chain Reaction , Sequence Analysis, DNA
11.
J Phys Chem A ; 117(29): 6126-42, 2013 Jul 25.
Article in English | MEDLINE | ID: mdl-23496231

ABSTRACT

The origin band of the Ã1B2-X1A1 (π* ← π) absorption system in monodeuterated tropolone (TrOD) has been probed with near-rotational resolution by applying the frequency-domain techniques of polarization-resolved degenerate four-wave mixing (DFWM) spectroscopy under ambient, bulk-gas conditions. Judicious selection of polarization geometries for the incident and detected electromagnetic waves alleviated intrinsic spectral congestion and facilitated dissection of overlapping transitions, thereby enabling refined rotational-tunneling parameters to be extracted for the Ã1B2(π*π) manifold. A tunneling-induced bifurcation of Δ0à = 2.241(14) cm(-1) was measured for the zero-point level of electronically excited TrOD, reflecting the presence of a substantial barrier along the O-D···O ↔ O···D-O reaction coordinate and representing nearly a 10-fold decrease in magnitude over the analogous quantity in the parent (TrOH) isotopologue. Observed trends in hydron-migration rates are discussed in light of the changes in the potential-surface topology sustained from the π* ← π electron promotion and the dynamical effects incurred by selective isotopic modification of the nuclear framework, with similar considerations being applied to interpret rotational constants and inertial defects. Simultaneous analyses performed on an interloping sequence band built upon ν38(b1) gave an excited-state tunneling splitting of Δ(ν38)à = 1.217(61) cm(-1), highlighting the ability of this symmetric, out-of-plane normal mode to inhibit the unimolecular tautomerization process.

12.
J Neuroophthalmol ; 32(2): 116-23, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22269944

ABSTRACT

BACKGROUND: Benign multiple sclerosis (MS), traditionally defined as Expanded Disability Status Scale (EDSS) score ≤3 and ≥15-year disease duration, is thought to follow a milder clinical course. We determined the extent of visual pathway axonal loss by optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness in a benign MS cohort and examined the relation to vision and quality of life (QOL). METHODS: In this longitudinal study of vision in MS at 3 academic centers, a subset of patients with EDSS, visual function, OCT, and QOL assessments was analyzed. Low- and high-contrast letter acuity was performed to assess visual function. RNFL thickness was determined using time-domain OCT. QOL scales included the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Short Form-36 Health Survey. RESULTS: Among 68 patients (135 eyes) studied longitudinally, 13 (26 eyes) had benign MS using criteria of EDSS score ≤3 and ≥15-year disease duration. Benign MS eyes had as much RNFL thinning (-3.6 µm, P = 0.0008 vs baseline, paired t test) as typical MS eyes (-3.3 µm, P < 0.0001). Both groups had significant low-contrast acuity loss. History of optic neuritis (ON) was more frequent in benign MS (69% vs 33% of eyes). History of ON distinguished benign vs typical MS (P = 0.002) and correlated with RNFL thickness at baseline (P = 0.002) and disease duration (P = 0.03) but not EDSS (P = 0.32, logistic regression). NEI-VFQ-25 scores were also worse for benign MS, accounting for age (75 ± 21 vs 88 ± 11, P = 0.005). CONCLUSION: Patients with benign MS have RNFL axonal loss that is as marked as that of typical MS and have reduced vision and QOL. While overall neurologic impairment is mild, visual dysfunction, not well captured by the EDSS, accounts for a substantial degree of disability in benign MS.


Subject(s)
Multiple Sclerosis/physiopathology , Tomography, Optical Coherence/methods , Visual Pathways/physiopathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multiple Sclerosis/diagnosis , Prospective Studies , Quality of Life , Retinal Ganglion Cells/pathology , Surveys and Questionnaires , Visual Acuity , Visual Pathways/pathology
13.
Ann Neurol ; 67(6): 749-60, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20517936

ABSTRACT

OBJECTIVE: Cross-sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON). METHODS: Patients underwent OCT measurement of RNFL thickness at baseline and at 6-month intervals during a mean follow-up of 18 months at 3 centers. Low-contrast letter acuity (2.5%, 1.25% contrast) and visual acuity (VA) were assessed. RESULTS: Among 299 patients (593 eyes) with >or=6 months follow-up, eyes with visual loss showed greater RNFL thinning compared to eyes with stable vision (low-contrast acuity, 2.5%: p < 0.001; VA: p = 0.005). RNFL thinning increased over time, with average losses of 2.9microm at 2 to 3 years and 6.1microm at 3 to 4.5 years (p < 0.001 vs 0.5-1-year follow-up interval). These patterns were observed for eyes with or without prior history of ON. Proportions of eyes with RNFL loss greater than test-retest variability (>or=6.6microm) increased from 11% at 0 to 1 year to 44% at 3 to 4.5 years (p < 0.001). INTERPRETATION: Progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON, and is associated with clinically significant visual loss. These findings are consistent with subclinical axonal loss in the anterior visual pathway in MS, and support the use of OCT and low-contrast acuity as methods to evaluate the effectiveness of putative neuroprotection protocols.


Subject(s)
Multiple Sclerosis/complications , Multiple Sclerosis/pathology , Nerve Fibers/pathology , Neurons/pathology , Retina/pathology , Vision Disorders/etiology , Adult , Cross-Sectional Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Tomography, Optical Coherence/methods , Visual Acuity/physiology
14.
J Phys Chem A ; 114(18): 5728-42, 2010 May 13.
Article in English | MEDLINE | ID: mdl-20394448

ABSTRACT

Infrared spectra obtained in gas and liquid argon phases are reported for (12)CF(2) horizontal line(12)CH(2) and (12)CF(2) horizontal line(13)CH(2). These spectra firmly establish the positions of nu(3)(A(1)) and nu(6)(A(2)) for both isotopomers. Using anharmonicity constants from MP2 calculations, Fermi resonances affecting nu(1)(A(1)), nu(2)(A(1)), nu(3), and nu(8)(B(1)) are analyzed. Deperturbed fundamental frequencies from these analyses are used in conjunction with unaffected fundamentals and ab initio anharmonicity data to predict all 12 "observed" harmonic frequencies. A Darling-Dennison type resonance between 2nu(6) and nu(11) + nu(12) is diagnosed, the calculation of which from ab initio data requires modification of the existing second-order treatment of such constants, where Fermi resonance type terms are also present. Predictions are made of many overtone and combination band frequencies, aiding assignment of observed spectra. From the isolated CH stretching frequency obtained here of 3125.4 cm(-1), the C-H equilibrium bond length is predicted to be 1.0762(11) A.

15.
J Phys Chem A ; 111(13): 2498-506, 2007 Apr 05.
Article in English | MEDLINE | ID: mdl-17388345

ABSTRACT

IR and Raman spectra are reported for 1,1-difluorocyclopropane-d0, -d2, and -d4, and complete assignments of vibrational fundamentals are given for these species. These assignments are consistent with predictions of frequencies, intensities, and Raman depolarization ratios computed with the B3LYP/cc-pVTZ quantum chemical (QC) model. Ground state rotational constants for five 13C and deuterium isotopomers, obtained from published microwave spectra, were "corrected" into equilibrium rotational constants. The needed vibration-rotation interaction constants were computed with QC models after scaling the force constants. A semi-experimental equilibrium structure, fitted to the equilibrium moments of inertia, is rC1C = 1.470(1) A, rCC = 1.546(1) A, rCF = 1.343(1) A, rCH = 1.078(1) A, alphaFCF = 109.5(1), alphaFCC = 119.4(1) degrees, alphaHCH = 116.7(1) degrees, alphaC1CH = 117.4(1) degrees, and alphaCCH = 117.1(1) degrees. This structure agrees within the indicated uncertainties with the ab initio structure obtained from an extrapolated set of CCSD(T)/aug-cc-pVnZ calculations except for rCC = 1.548 A. The F2C-CH2 bonds are significantly shortened and strengthened; the H2C-CH2 bond is significantly lengthened and weakened.

16.
Biochemistry ; 45(32): 9804-18, 2006 Aug 15.
Article in English | MEDLINE | ID: mdl-16893181

ABSTRACT

Replication protein A (RPA) is an essential heterotrimeric ssDNA binding protein that participates in DNA repair, replication, and recombination. Though X-ray and NMR experiments have been used to determine three-dimensional structure models of the protein's domain fragments, a complete RPA structural model has not been reported. To test whether the fragment structures faithfully represent the same portions in the native solution-state protein, we have examined the structure of RPA under biologically relevant conditions. We have probed the location of multiple amino acids within the native RPA three-dimensional structure using reactivity of these amino acids toward proteolytic and chemical modification reagents. In turn, we evaluated different structural models by comparing the observed native RPA reactivities with anticipated reactivities based on candidate structural models. Our results show that our reactivity analysis approach is capable of critically assessing structure models and can be a basis for selecting the most relevant from among alternate models of a protein structure. Using this analytical approach, we verified the relevance of RPA fragment models to the native protein structure. Our results further indicate several important features of native RPA's structure in solution, such as flexibility at specific locations in RPA, particularly in the C-terminal region of RPA70. Our findings are consistent with reported DNA-free structural models and support the role of conformational change in the ssDNA binding mechanism of RPA.


Subject(s)
Replication Protein A/chemistry , Amino Acid Sequence , Binding Sites , DNA/metabolism , Free Radicals/metabolism , Humans , Hydroxylation , Kinetics , Mass Spectrometry , Models, Molecular , Peptides/chemistry , Protein Binding , Protein Structure, Tertiary , Time Factors
17.
Br J Cancer ; 91(5): 942-53, 2004 Aug 31.
Article in English | MEDLINE | ID: mdl-15292939

ABSTRACT

Cytology and histology records and cervical samples for HPV assay were obtained from a prospective cohort of 49 655 women attending clinics for routine cervical cytology in or near Manchester between 1988 and 1993. The women were followed up for cytological abnormality and neoplasia through the cytology laboratory's records. HPV at entry was assayed in an age- and period-stratified random sample of 7278 women and in prevalent and incident CIN3 cases. The prevalence of newly diagnosed CIN3 increased with time since last normal smear, indicating that most cases persist for several years. CIN3 prevalence did not increase further for screening intervals exceeding 5 years, however, suggesting that CIN3 eventually regresses cytologically. CIN2 prevalence increased less steeply with screening interval, while the prevalence of lesser abnormality was almost independent of screening interval. The prevalence of oncogenic HPV at entry declined from 19% among women aged under 25 to less than 3% at age 40 or above. Oncogenic HPV infection was strongly predictive of subsequent CIN3 (OR 17.2, 95% CI 10.4-28.4), but only weakly related to CIN2 (OR 2.3, 95% CI 0.5-10.7) and lesser abnormality (OR 1.4, 95% CI 0.8-2.5). At current incidence rates, the lifetime risk of developing CIN3 will be 9% in this population. The cumulative risk of CIN3 diagnosis among cytologically normal women with oncogenic HPV detected at entry was 28% (CI 18-43%) after 14 years. Persistence of oncogenic HPV may be more sensitive and specific than cytology for early detection of CIN3 and invasive cancer.


Subject(s)
DNA, Viral/isolation & purification , Papillomavirus Infections/complications , Tumor Virus Infections/complications , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/virology , Adolescent , Adult , Age Factors , Aged , Female , Humans , Mass Screening , Middle Aged , Papillomaviridae , Papillomavirus Infections/epidemiology , Polymerase Chain Reaction , Prevalence , Prospective Studies , Risk Factors , Sensitivity and Specificity , Tumor Virus Infections/epidemiology , United Kingdom/epidemiology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Vaginal Smears , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/prevention & control
18.
Br J Cancer ; 89(11): 2078-86, 2003 Dec 01.
Article in English | MEDLINE | ID: mdl-14647141

ABSTRACT

We report results on risk factors for invasive squamous cell and adenocarcinomas of the cervix in women aged 20-44 years from the UK National Case-Control Study of Cervical Cancer, including 180 women with adenocarcinoma, 391 women with squamous cell carcinoma and 923 population controls. The risk of both squamous cell and adenocarcinoma was strongly related to the lifetime number of sexual partners, and, independently, to age at first intercourse. The risk of both types of cervical cancer increased with increasing duration of use of oral contraceptives, and this effect was most marked in current and recent users of oral contraceptives. The risk of squamous cell carcinoma was associated with high parity and the risk of both squamous cell and adenocarcinoma increased with early age at first birth. Long duration smoking (20 or more years) was associated with a two-fold increase in the risk of squamous cell carcinoma, but smoking was not associated with the risk of adenocarcinoma. Further studies are needed to confirm the suggestion from this and other studies of differences in risk related to smoking between squamous cell and adenocarcinomas of the cervix.


Subject(s)
Adenocarcinoma/etiology , Carcinoma, Squamous Cell/etiology , Uterine Cervical Neoplasms/etiology , Adult , Case-Control Studies , Contraceptives, Oral/adverse effects , Female , Humans , Parity , Risk Factors , Smoking/adverse effects , United Kingdom
19.
Antonie Van Leeuwenhoek ; 83(3): 235-43, 2003.
Article in English | MEDLINE | ID: mdl-12776919

ABSTRACT

The behaviour of encysting zoospores of Phytophthora palmivora during leaching conditions was studied. Zoospores encysted and germinated successfully on polycarbonate membranes after mechanical agitation. Transient (10 min) leaching treatments with nutrient-free buffer underneath the membranes resulted in abnormal encystment and poor germination. The disruption was greatest when leaching was applied during the first minutes after start of encystment and not observed after 20 min. The early sensitivity of cells to leaching coincided with the period when alkali-resistant cell walls were formed (2-6 min after mechanical agitation). Effects of calcium and organic nutrients on encystment during leaching and germination after these treatments were studied. The disruption of encystment by early leaching treatments, but not the suppression of cyst germination, was overcome by adding calcium chloride during mechanical agitation of zoospores. Leaching with calcium containing buffer resulted in suppressed cyst germination as was the case with buffer alone. Leaching with 0.1% peptone containing buffer promoted consistently high encystment and germination.


Subject(s)
Phytophthora/physiology , Spores, Fungal/physiology , Buffers , Calcium/metabolism , Cell Wall/metabolism , Peptones/metabolism , Random Allocation
20.
Br J Cancer ; 87(11): 1257-66, 2002 Nov 18.
Article in English | MEDLINE | ID: mdl-12439715

ABSTRACT

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one.


Subject(s)
Central Nervous System Neoplasms/etiology , Electromagnetic Fields/adverse effects , Environmental Exposure , Leukemia/etiology , Adolescent , Case-Control Studies , Central Nervous System Neoplasms/epidemiology , Child , Child Welfare , Child, Preschool , Female , Housing , Humans , Incidence , Infant , Infant, Newborn , Leukemia/epidemiology , Male , Neoplasms/epidemiology , Neoplasms/etiology , Odds Ratio , Pilot Projects , Risk Assessment , United Kingdom/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL