Coverage and Access for Americans with Cardiovascular Disease or Risk Factors After the ACA: a Quasi-experimental Study.

BACKGROUND: Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the USA. Many with CVD or cardiovascular risk factors (CVRFs) lacked insurance coverage and access to care before enactment of the Affordable Care Act (ACA). OBJECTIVE: To assess the effect of the ACA on insurance coverage, access to care, and racial/ethnic disparities among non-elderly adults with CVD or CVRFs. DESIGN: Quasi-experimental policy intervention. PARTICIPANTS: Nationally representative, non-institutionalized sample of 1,014,450 adults aged 18 to 64 years with CVD or at least 2 established CVRFs in the pre-ACA (2012-2013) and post-ACA (2015-2016) periods. INTERVENTION: Implementation of ACA provisions on 1 January 2014. MAIN MEASURES: Insurance coverage, having a check-up, having a personal physician, and not having to forgo a needed physician visit because of cost. KEY RESULTS: Following ACA implementation, insurance coverage increased by 6.9 percentage points (95% CI, 6.6 to 7.2), not having to forgo a physician visit increased by 3.6 percentage points (CI, 3.3 to 3.9), having a check-up increased by 2.1 percentage points (CI, 1.8 to 2.6), and having a personal physician increased by 1 percentage point (0.6 to 1.3); changes were approximately doubled for those with lower incomes (< $35,000/year). Changes in coverage varied substantially by state and all outcomes improved more in Medicaid expansion states. Although racial/ethnic minorities had greater improvements in some outcomes, approximately 13% black and 29% Hispanic adults continued to lack coverage and access to care post-ACA. CONCLUSION: The ACA increased coverage and access for adults with CVD or multiple CVRFs; substantial gaps remain, particularly for minorities and those in Medicaid non-expansion states.

Imported case of measles in a university setting leading to an outbreak of measles in Edinburgh, Scotland from September to December 2016.

In September 2016, an imported case of measles in Edinburgh in a university student resulted in a further 17 confirmed cases during October and November 2016. All cases were genotype D8 and were associated with a virus strain most commonly seen in South East Asia. Twelve of the 18 cases were staff or students at a university in Edinburgh and 17 cases had incomplete or unknown measles mumps rubella (MMR) vaccination status. The public health response included mass follow-up of all identified contacts, widespread communications throughout universities in Edinburgh and prompt vaccination clinics at affected campuses. Imported cases of measles pose a significant risk to university student cohorts who may be undervaccinated, include a large number of international students and have a highly mobile population. Public health departments should work closely with universities to promote MMR uptake and put in place mass vaccination plans to prevent rapidly spreading measles outbreaks in higher educational settings in future.

Single-shot mega-electronvolt ultrafast electron diffraction for structure dynamic studies of warm dense matter.

We have developed a single-shot mega-electronvolt ultrafast-electron-diffraction system to measure the structural dynamics of warm dense matter. The electron probe in this system is featured by a kinetic energy of 3.2 MeV and a total charge of 20 fC, with the FWHM pulse duration and spot size at sample of 350 fs and 120 µm respectively. We demonstrate its unique capability by visualizing the atomic structural changes of warm dense gold formed from a laser-excited 35-nm freestanding single-crystal gold foil. The temporal evolution of the Bragg peak intensity and of the liquid signal during solid-liquid phase transition are quantitatively determined. This experimental capability opens up an exciting opportunity to unravel the atomic dynamics of structural phase transitions in warm dense matter regime.

Maternal morbid obesity: financial implications of weight management.

The objective of this study was to evaluate health outcomes and costs of pregnancies complicated by extreme maternal obesity (class III obesity, body mass index ≥ 40). We conducted a retrospective case-control descriptive study comparing extremely obese women (cases) and their infants with randomly selected controls. Health outcomes were obtained from the medical records and costs from billing data. Total costs for each mother-infant dyad were calculated. Compared with 85 controls, the 82 cases experienced higher morbidity, higher costs and prolonged hospital stay. However, 26% of cases maintained or lost weight during pregnancy, whereas none of the controls maintained or lost weight during pregnancy. When mother/infant dyads were compared on costs, case subjects who maintained or lost weight experienced lower costs than those who gained weight. Neonatal intensive care consumed 78% of total hospital costs for infants of the obese women who gained weight, but only 48% of costs for infants of obese women who maintained or lost weight. For extremely obese women, weight management during pregnancy was achievable, resulted in healthier neonatal outcomes and reduced perinatal healthcare costs.

Mega-electron-volt ultrafast electron diffraction at SLAC National Accelerator Laboratory.

Ultrafast electron probes are powerful tools, complementary to x-ray free-electron lasers, used to study structural dynamics in material, chemical, and biological sciences. High brightness, relativistic electron beams with femtosecond pulse duration can resolve details of the dynamic processes on atomic time and length scales. SLAC National Accelerator Laboratory recently launched the Ultrafast Electron Diffraction (UED) and microscopy Initiative aiming at developing the next generation ultrafast electron scattering instruments. As the first stage of the Initiative, a mega-electron-volt (MeV) UED system has been constructed and commissioned to serve ultrafast science experiments and instrumentation development. The system operates at 120-Hz repetition rate with outstanding performance. In this paper, we report on the SLAC MeV UED system and its performance, including the reciprocal space resolution, temporal resolution, and machine stability.

Does rheumatoid arthritis disease activity correlate with weather conditions?

To determine whether rheumatoid arthritis disease activity correlates with changing weather conditions. A longitudinal analysis of 133 patients attending the Department of Rheumatology, Musgrave Park Hospital, Belfast was performed. Participants had a diagnosis of rheumatoid arthritis and were receiving subcutaneous anti-TNF therapy (Adalimumab or Etanercept) for a period of >6 months. Data were collected at five time points. This included tender joint count, swollen joint count, patient visual analogue score (VAS), erythrocyte sedimentation rate, C-reactive protein, VAS, and DAS-28 (Disease Activity Score). Each weather factor (maximum, minimum temperature, pressure, rainfall, sunshine, humidity, and wind-speed) was analysed against each patients' DAS-28 score at five time points, using an analysis of covariance. A significant correlation was noted between low DAS-28 and increased hours of sunshine (p < 0.001). Sunny conditions were associated with a DAS-28 reduction of 0.037 (95 % CI -0.059, -0.016) p < 0.001. A significant correlation between humidity and DAS-28 was also noted (p = 0.016). Increased humidity was associated with an increased DAS-28 of 0.007 (95 % CI 0.001, 0.013) p = 0.016. Higher temperatures were associated with a non-significant decrease in DAS-28 (p = 0.16). In this study, rheumatoid arthritis disease activity (as measured by DAS-28) was significantly lower in both more sunny and less humid conditions.

The effect of a large Legionnaires' disease outbreak in Southwest Edinburgh on acute and critical care services.

OBJECTIVE: The largest outbreak of Legionnaires Disease (LD) in the UK for a decade occurred in Edinburgh in June 2012. We describe the clinical and public health management of the outbreak. SETTING: Three acute hospitals covering an urban area of ~480,000. METHODS: Data were collected on confirmed and suspected cases and minutes of the Incident Management Team meetings were reviewed to identify key actions. RESULTS: Over 1600 urine samples and over 600 sputum samples were tested during the outbreak. 61 patients with pneumonia tested positive for Legionella pneumophila serogroup 1 by urinary antigen detection, culture, respiratory PCR or serology. A further 23 patients with pneumonia were treated as suspected cases on clinical and epidemiological grounds but had no microbiological diagnosis. 36% of confirmed and probable cases required critical care admission. Mean ICU length of stay was 11.3 (±7.6) days and mean hospital length of stay for those who were admitted to ICU was 23.0 (±17.2) days. For all hospitalized patients the mean length of stay was 15.7 (±14) days. In total there were four deaths associated with this outbreak giving an overall case fatality of 6.5%. Hospital and critical care mortality was 6.1% and 9.1%, respectively. CONCLUSION: A significant proportion of patients required prolonged multiple organ support or complex ventilation. Case fatality compared favourably to other recent outbreaks in Europe. Access to rapid diagnostic tests and prompt antibiotic therapy may have mitigated the impact of pre-existing poor health among those affected.

The ventriculocholecystic shunt: two case reports and a review of the literature.

We describe the re-siting of ventriculoperitoneal shunts to the gallbladder in two children. The first child had a rare case of hydrocephalus associated with plasminogen deficiency. She had had multiple VP shunt revisions due to non-absorption of CSF from the peritoneum. The second had craniopharyngioma-related hydrocephalus with once again a non-absorbing peritoneum. We report no surgical complications in the revisions for both the cases, and there has been a subsequent follow-up of 46 and 28 months, respectively, without incident. A review of the relevant literature describing the use and the performance of ventriculocholecystic shunts in comparison with other ventricular shunts is considered.

Generating periodic terahertz structures in a relativistic electron beam through frequency down-conversion of optical lasers.

We report generation of density modulation at terahertz (THz) frequencies in a relativistic electron beam through laser modulation of the beam longitudinal phase space. We show that by modulating the energy distribution of the beam with two lasers, density modulation at the difference frequency of the two lasers can be generated after the beam passes through a chicane. In this experiment, density modulation around 10 THz was generated by down-converting the frequencies of an 800 nm laser and a 1550 nm laser. The central frequency of the density modulation can be tuned by varying the laser wavelengths, beam energy chirp, or momentum compaction of the chicane. This technique can be applied to accelerator-based light sources for generation of coherent THz radiation and marks a significant advance toward tunable narrow band THz sources.

Public health response to an outbreak of Legionnaires' disease in Edinburgh, United Kingdom, June 2012.

We report an outbreak comprising 50 confirmed cases of Legionnaires' disease in Edinburgh, Scotland, June 2012. In addition, there were 49 suspected cases. Epidemiological evidence suggests that a common outdoor airborne exposure occurred over south-west Edinburgh. This probably emanated from cooling towers in the north-east of the affected area, although not yet clearly linked by scientific evidence. The co-ordinated public health, environmental and clinical response helped prevent ongoing exposure and mitigated associated mortality and morbidity.

Evidence of high harmonics from echo-enabled harmonic generation for seeding x-ray free electron lasers.

Echo-enabled harmonic generation free electron lasers hold great promise for the generation of fully coherent radiation in x-ray wavelengths. Here we report the first evidence of high harmonics from the echo-enabled harmonic generation technique in the realistic scenario where the laser energy modulation is comparable to the beam slice energy spread. In this experiment, coherent radiation at the seventh harmonic of the second seed laser is generated when the energy modulation amplitude is about 2-3 times the slice energy spread. The experiment confirms the underlying physics of echo-enabled harmonic generation and may have a strong impact on emerging seeded x-ray free electron lasers that are capable of generating laserlike x rays which will advance many areas of science.

Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity.

To characterize the subchronic oral toxicity of resveratrol, CD rats received daily gavage doses of 0, 200, 400, or 1000 mg resveratrol/kg/day, and beagle dogs received daily capsule doses of 0, 200, 600, or 1200 mg resveratrol/kg/day for 90 days. Resveratrol induced only minimal toxicity, consisting of dose-related reductions in body weight gain in female rats and both sexes of dogs, and a statistically significant increase in bilirubin levels in rats at the 1000 mg/kg/day dose. Clinical observations, hematology, ophthalmology, neurotoxicity evaluations (functional observational batteries), organ weights, and gross pathology provided no biologically significant evidence of resveratrol toxicity in either species. In rats, the high dose of resveratrol reduced the incidence of cardiomyopathy; no other microscopic changes were seen. Histopathologic changes in dogs were limited to minimal inflammatory infiltrates in the kidney and urinary bladder, which were not considered toxicologically significant. A cardiovascular safety pharmacology (telemetry) study in dogs revealed no evidence of resveratrol toxicity. Based on body weight effects, the No Observed Adverse Effect Level (NOAEL) for resveratrol was 200mg/kg/day in rats and 600 mg/kg/day in dogs. The apparent cardioprotective activity of resveratrol in rats demonstrates that its potentially beneficial activities may extend beyond efficacy in cancer prevention.

Demonstration of the echo-enabled harmonic generation technique for short-wavelength seeded free electron lasers.

We report the first experimental demonstration of the echo-enabled harmonic generation technique, which holds great promise for generation of high-power, fully coherent short-wavelength radiation. In this experiment, coherent radiation at the 3rd and 4th harmonics of the second seed laser is generated from the so-called beam echo effect. The experiment confirms the physics behind this technique and paves the way for applying the echo-enabled harmonic generation technique for seeded x-ray free electron lasers.

Subchronic oral toxicity studies of Se-methylselenocysteine, an organoselenium compound for breast cancer prevention.

Se-methylselenocysteine (MSC) is an organoselenium compound being developed for breast cancer chemoprevention. To characterize MSC toxicity, CD rats received daily gavage doses of 0, 0.5, 1.0, or 2.0 mg/kg/day (0, 3, 6, or 12 mg/m(2)/day), and beagle dogs received daily gavage doses of 0, 0.15, 0.3, or 0.6 mg/kg/day (0, 3, 6, or 12 mg/m(2)/day) for 28 days. In rats, MSC induced dose-related hepatomegaly in both sexes; mild anemia, thrombocytopenia, and elevated liver enzymes were observed in high dose females only. Microscopic pathology included hepatocellular degeneration (high dose males, all doses in females); arrested spermatogenesis (high dose males); and atrophy of corpora lutea (middle and high dose females). In dogs, MSC induced mild anemia in middle and high dose males, and in high dose females. Toxicologically significant microscopic lesions in dogs were seen only in the liver (peliosis and vacuolar degeneration in high dose males, midzonal necrosis in males in all dose groups). Based on liver pathology seen in female rats in all dose groups, the no observed adverse effect level (NOAEL) for MSC in rats is <0.5mg/kg/day. Based on alterations in hematology parameters and liver morphology in male dogs in all dose groups, the NOAEL for MSC in dogs is <0.15 mg/kg/day.

Structure-activity relationship development of dihaloaryl triazole compounds as insecticides and acaricides. 1. Phenyl thiophen-2-yl triazoles.

An extended lipophilic system that incorporated some key elements of first-generation 2,6-dihaloaryl actives, such as 1, demonstrated desirable efficacy against chewing insects as well as sap-feeding insects. These four-ring systems, based on 2, were accessed primarily via Suzuki couplings of halothiophene derivatives with appropriately substituted boronic acids. In particular, phenylthiophene systems that incorporated haloxyether groups, such as those in 3, 4, and 5, had the broadest spectrum of activity across chewing and sap-feeding insect pests. Expansion of this structure-activity relationship to include compounds with differing substitution patterns on the thiophene-C-ring and aryl-D-rings was undertaken. The synthesis and insecticidal activity of 3-aryl-5-(thiophen-2-yl)-1-methyl-1H-[1,2,4]triazoles will be described.

Mechanisms of local immunosuppression in cutaneous melanoma.

Cutaneous melanoma is highly immunogenic, yet primary melanomas and metastases develop successfully in otherwise immunocompetent patients. To investigate the local immunosuppressive microenvironment, we examined the presence of suppressor T lymphocytes and tolerising dendritic cells (DCs), the expression of immunosuppressive cytokines (IL-10, TGFbeta1 and TGFbeta2) and the enzyme indoleamine 2,3-dioxygenase (IDO) using qRT-PCR and immunohistochemistry in primary skin melanomas, negative and positive sentinel lymph nodes (SLN), and lymph nodes with advanced metastases. Our results indicate that tolerogenic DCs and suppressor T lymphocytes are present in melanoma at all stages of disease progression. They express transforming growth factor beta receptor 1 (TGFbetaR1), and are therefore susceptible to TGFbeta1 and TGFbeta2 specifically expressed by primary melanoma. We found that expression of IDO and interleukin 10 (IL-10) increased with melanoma progression, with the highest concentration in positive SLN. We suggest that negative SLN contain immunosuppressive cells and cytokines, due to preconditioning by tolerogenic DCs migrating from the primary melanoma site to the SLN. In primary melanoma, TGFbeta2 is likely to render peripheral DCs tolerogenic, while in lymph nodes IDO and TGFbeta1 may have a major effect. This mechanism of tumour-associated immunosuppression may inhibit the immune response to the tumour and may explain the discrepancy between the induction of systemic immunity by anti-melanoma vaccines and their poor performance in the clinic.

Oncogenicity evaluation of resveratrol in p53(+/-) (p53 knockout) mice.

A six-month study was conducted in p53(+/-) mice to evaluate the possible oncogenicity of resveratrol (3,5,4'-trihydroxy-trans-stilbene), a cancer chemopreventive agent present in grapes and other foods. p53(+/-) mice (25/sex/group) received daily gavage exposure to vehicle only (negative control), resveratrol doses of 1000, 2000, or 4000 mg/kg/day, or p-cresidine (400 mg/kg/day; positive control). No mortality was seen in mice receiving the low dose of resveratrol. However, the mid and high doses induced mortality associated with impaction of the test article in the gastrointestinal tract. Resveratrol had no effect on body weight, food consumption, or clinical signs in surviving mice in any dose group, but induced dose-related increases in liver weight and serum cholesterol in both sexes. Mild anemia was seen in male mice at the high dose only; hematologic effects were not seen in females. Histopathology identified the kidney (hydronephrosis) and urinary bladder (epithelial hyperplasia) as target tissues for resveratrol toxicity. The incidences of both benign and malignant tumors in mice exposed to resveratrol were comparable to those in vehicle controls. By contrast, the positive control article, p-cresidine, induced urinary bladder cancer in both sexes. When administered to p53(+/-) mice at its maximum tolerated dose, resveratrol demonstrates no evidence of oncogenicity.

Cortactin underpins CD44-promoted invasion and adhesion of breast cancer cells to bone marrow endothelial cells.

Using a validated tetracycline (tet)-regulated MCF7-founder (MCF7F) expression system to modulate expression of CD44 standard form (CD44s), we report the functional importance of CD44s and that of a novel transcriptional target of hyaluronan (HA)/CD44s signaling, EMS1/cortactin, in underpinning breast cancer metastasis. In functional experiments, tet-regulated induction of CD44s potentiated the migration and invasion of MCF7F cells through HA-supplemented Matrigel. EMS1/cortactin was identified by expression profiling as a novel transcriptional target of HA/CD44 signaling, an association validated by quantitative PCR and immunoblotting experiments in a range of breast cancer cell lines. The mechanistic basis underpinning CD44-promoted transcription of EMS1/cortactin was shown to be dependent upon a NFkappaB mechanism, since pharmacological inhibition of IkappaKinase-2 or suppression of p65 Rel A expression attenuated CD44-induced increases in cortactin mRNA transcript levels. Overexpression of a c-myc tagged murine cortactin construct in the weakly invasive, CD44-deficient MCF7F and T47D cells potentiated their invasion. Furthermore, the functional importance of cortactin to CD44s-promoted metastasis was demonstrated by selective suppression of cortactin in CD44-expressing MCF7F-B5 and MDA-MB-231 breast cancer cells using RNAi, which was shown to result in attenuated CD44-promoted invasion and CD44-promoted adhesion to bone marrow endothelial cells (BMECs).

Prognostic significance of glycoprotein pMQ1 in breast cancer.

BACKGROUND: A novel glycoprotein, pMQ1, is positively correlated with increasing histological grade in malignant astrocytomas. Cerebral metastases from breast cancer have also been found to contain pMQ1-positive cells. This study aimed to determine the role of pMQ1 in primary breast cancer. METHODS: Breast cancer specimens were analysed for pMQ1 by immunohistochemistry. The expression of pMQ1 was correlated with conventional prognostic indicators. Kaplan-Meier analyses were performed to compare clinical outcome between pMQ1-positive and pMQ1-negative tumours. RESULTS: pMQ1 was expressed in most of the breast cancer specimens. The surrounding normal tissue margins and benign breast tissues always lacked pMQ1 expression. A significant positive correlation was observed between pMQ1 expression and histological grade, the presence of lymphovascular invasion and Nottingham Prognostic Index. Cancers that were pMQ1 positive were significantly more likely to develop a local recurrence. CONCLUSION: pMQ1 appears to be a tumour-associated protein. The positive correlation of pMQ1 with histological grade, presence of lymphovascular invasion and Nottingham Prognostic Index suggests that it confers an adverse prognosis.