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.

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 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.

Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis.

Papillon-Lefèvre syndrome, or keratosis palmoplantaris with periodontopathia (PLS, MIM 245000), is an autosomal recessive disorder that is mainly ascertained by dentists because of the severe periodontitis that afflicts patients. Both the deciduous and permanent dentitions are affected, resulting in premature tooth loss. Palmoplantar keratosis, varying from mild psoriasiform scaly skin to overt hyperkeratosis, typically develops within the first three years of life. Keratosis also affects other sites such as elbows and knees. Most PLS patients display both periodontitis and hyperkeratosis. Some patients have only palmoplantar keratosis or periodontitis, and in rare individuals the periodontitis is mild and of late onset. The PLS locus has been mapped to chromosome 11q14-q21 (refs 7, 8, 9). Using homozygosity mapping in eight small consanguineous families, we have narrowed the candidate region to a 1.2-cM interval between D11S4082 and D11S931. The gene (CTSC) encoding the lysosomal protease cathepsin C (or dipeptidyl aminopeptidase I) lies within this interval. We defined the genomic structure of CTSC and found mutations in all eight families. In two of these families we used a functional assay to demonstrate an almost total loss of cathepsin C activity in PLS patients and reduced activity in obligate carriers.

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.

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.

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.

Thalamocortical oscillations in the sleeping and aroused brain.

Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis of cortical and thalamic networks at many levels, from molecules to single neurons to large neuronal assemblies, with a variety of techniques, ranging from intracellular recordings in vivo and in vitro to computer simulations, is beginning to yield insights into the mechanisms of the generation, modulation, and function of brain oscillations.

Cellular mechanisms of a synchronized oscillation in the thalamus.

Spindle waves are a prototypical example of synchronized oscillations, a common feature of neuronal activity in thalamic and cortical systems in sleeping and waking animals. Spontaneous spindle waves recorded from slices of the ferret lateral geniculate nucleus were generated by rebound burst firing in relay cells. This rebound burst firing resulted from inhibitory postsynaptic potentials arriving from the perigeniculate nucleus, the cells of which were activated by burst firing in relay neurons. Reduction of gamma-aminobutyric acidA (GABAA) receptor-mediated inhibition markedly enhanced GABAB inhibitory postsynaptic potentials in relay cells and subsequently generated a slowed and rhythmic population activity resembling that which occurs during an absence seizure. Pharmacological block of GABAB receptors abolished this seizure-like activity but not normal spindle waves, suggesting that GABAB antagonists may be useful in the treatment of absence seizures.

Chattering cells: superficial pyramidal neurons contributing to the generation of synchronous oscillations in the visual cortex.

In response to visual stimulation, a subset of neurons in the striate and prestriate cortex displays synchronous rhythmic firing in the gamma frequency band (20 to 70 hertz). This finding has raised two fundamental questions: What is the functional significance of synchronous gamma-band activity and how is it generated? This report addresses the second of these two questions. By means of intracellular recording and staining of single cells in the cat striate cortex in vivo, a biophysically distinct class of pyramidal neuron termed "chattering cells" is described. These neurons are located in the superficial layers of the cortex, intrinsically generate 20- to 70-hertz repetitive burst firing in response to suprathreshold depolarizing current injection, and exhibit pronounced oscillations in membrane potential during visual stimulation that are largely absent during periods of spontaneous activity. These properties suggest that chattering cells may make a substantial intracortical contribution to the generation of synchronous cortical oscillations and thus participate in the recruitment of large populations of cells into synchronously firing assemblies.

Cerebellum: essential involvement in the classically conditioned eyelid response.

Classical conditioning of the eyelid response in the rabbit was used to investigate the neuronal structures mediating basic associative learning of discrete, adaptive responses. Lesions of the ipsilateral dentate-interpositus nuclei, but not of the cerebellar cortex, abolished the learned eyeblink response. Recordings from these nuclei have revealed neuronal responses related to the learning of the response. Stimulating these recording sites produced the eyelid response. The dentate-interpositus nuclei were concluded to be critically involved in the learning and production of classically conditioned responses.

Functional dynamics of GABAergic inhibition in the thalamus.

The inhibitory gamma-aminobutyric acid-containing (GABAergic) neurons of the thalamic reticular and perigeniculate nuclei are involved in the generation of normal and abnormal synchronized activity in thalamocortical networks. An important factor controlling the generation of activity in this system is the amplitude and duration of inhibitory postsynaptic potentials (IPSPs) in thalamocortical cells, which depend on the pattern of activity generated in thalamic reticular and perigeniculate cells. Activation of single ferret perigeniculate neurons generated three distinct patterns of GABAergic IPSPs in thalamocortical neurons of the dorsal lateral geniculate nucleus: Low-frequency tonic discharge resulted in small-amplitude IPSPs mediated by GABAA receptors, burst firing resulted in large-amplitude GABAA IPSPs, and prolonged burst firing activated IPSPs mediated by GABAA and GABAB receptors. These functional properties of GABAergic inhibition can reconfigure the operations of thalamocortical networks into patterns of activity associated with waking, slow-wave sleep, and generalized seizures.

What stops synchronized thalamocortical oscillations?

Slow-wave sleep as well as generalized absence seizures are characterized by the occurrence of synchronized oscillations in thalamocortical systems that spontaneously appear and disappear. The spontaneous appearance of synchronized oscillations results from the initiation by one or a small number of cells followed by the progressive recruitment of large numbers of neighboring neurons into the synchronized network activity. Synchronized network oscillations representative of slow-wave sleep, as well as absence seizures, were demonstrated to cease spontaneously at least in part through the persistent activation of a hyperpolarization-activated cation conductance. Block of this conductance resulted in oscillations that, once generalized, occur continuously. These results indicate that the persistent activation of a hyperpolarization-activated cation conductance is a key mechanism through which synchronized oscillations in thalamocortical networks normally terminate.

Periodicity of thalamic synchronized oscillations: the role of Ca2+-mediated upregulation of Ih.

Thalamocortical networks can generate both normal and abnormal patterns of synchronized network activity, such as spindle waves and spike-and-wave seizures. These periods of synchronized discharge are often separated by a silent, refractory phase of between 5 and 20 s. In vitro investigations have demonstrated that this refractory period is due in large part to the persistent activation of the hyperpolarization-activated cation current Ih in thalamocortical cells. Here, we show that increases in [Ca2+]i due to rebound Ca2+ bursts result in persistent activation of Ih resulting from a positive shift in the activation curve of this current. The dynamical upregulation and persistent activation of Ih is the critical determinant of the time course of the refractory period. These findings demonstrate that periodicity in neural network oscillations may be generated through an interaction between the electrophysiological properties and intracellular signaling pathways of the constituent neurons.

Abolition of spindle oscillations by serotonin and norepinephrine in the ferret lateral geniculate and perigeniculate nuclei in vitro.

The transition from sleep to waking is associated with the abolition of spindle waves in thalamocortical neurons and the GABAergic cells of the thalamic reticular/perigeniculate nuclei. We tested the possibility that norepinephrine (NE) and serotonin (5-HT) may abolish spindle wave generation through an enhancement of the hyperpolarization-activated cation current Ih in thalamocortical neurons. Local application of agents known to enhance Ih, including 5-HT, NE, the adenylyl cyclase activator, forskolin, and the beta-adrenergic agonist, isoproterenol, to lamina A1 of the dorsal lateral geniculate nucleus resulted in an abolition of local spindle wave generation in thalamocortical neurons. The abolition of spindle waves was reversed by the local application of the Ih channel blocker, cesium. These results suggest that NE and 5-HT may abolish the generation of spindle waves through the modulation of Ih in thalamocortical neurons.

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.

Brain calculus: neural integration and persistent activity.

Tank and colleagues make in vivo cellular recordings from neurons in a "neural integrator" of the goldfish involved in maintaining eye position. In this circuit, "working" memory may be the result of persistent changes in the state of the local network.

Cellular and network mechanisms of rhythmic recurrent activity in neocortex.

The neocortex generates periods of recurrent activity, such as the slow (0.1-0.5 Hz) oscillation during slow-wave sleep. Here we demonstrate that slices of ferret neocortex maintained in vitro generate this slow (< 1 Hz) rhythm when placed in a bathing medium that mimics the extracellular ionic composition in situ. This slow oscillation seems to be initiated in layer 5 as an excitatory interaction between pyramidal neurons and propagates through the neocortex. Our results demonstrate that the cerebral cortex generates an 'up' or depolarized state through recurrent excitation that is regulated by inhibitory networks, thereby allowing local cortical circuits to enter into temporarily activated and self-maintained excitatory states. The spontaneous generation and failure of this self-excited state may account for the generation of a subset of cortical rhythms during sleep.