Is there a clinically significant seasonal component to hospital admissions for atrial fibrillation?

BACKGROUND: Atrial fibrillation is a common cardiac dysrhythmia, particularly in the elderly. Recent studies have indicated a statistically significant seasonal component to atrial fibrillation hospitalizations. METHODS: We conducted a retrospective population cohort study using time series analysis to evaluate seasonal patterns of atrial fibrillation hospitalizations for the province of Ontario for the years 1988 to 2001. Five different series methods were used to analyze the data, including spectral analysis, X11, R-Squared, autocorrelation function and monthly aggregation. RESULTS: This study found evidence of weak seasonality, most apparent at aggregate levels including both ages and sexes. There was dramatic increase in hospitalizations for atrial fibrillation over the years studied and an age dependent increase in rates per 100,000. Overall, the magnitude of seasonal difference between peak and trough months is in the order of 1.4 admissions per 100,000 population. The peaks for hospitalizations were predominantly in April, and the troughs in August. CONCLUSIONS: Our study confirms statistical evidence of seasonality for atrial fibrillation hospitalizations. This effect is small in absolute terms and likely not significant for policy or etiological research purposes

Simplicity within complexity: Seasonality and predictability of hospital admissions in the province of Ontario 1988–2001, a population-based analysis

BACKGROUND: Seasonality is a common feature of communicable diseases. Less well understood is whether seasonal patterns occur for non-communicable diseases. The overall effect of seasonal fluctuations on hospital admissions has not been systematically evaluated. METHODS: This study employed time series methods on a population based retrospective cohort of for the fifty two most common causes of hospital admissions in the province of Ontario from 1988–2001. Seasonal patterns were assessed by spectral analysis and autoregressive methods. Predictive models were fit with regression techniques. RESULTS: The results show that 33 of the 52 most common admission diagnoses are moderately or strongly seasonal in occurrence; 96.5% of the predicted values were within the 95% confidence interval, with 37 series having all values within the 95% confidence interval. CONCLUSION: The study shows that hospital admissions have systematic patterns that can be understood and predicted with reasonable accuracy. These findings have implications for understanding disease etiology and health care policy and planning

Activation of p73 and induction of Noxa by DNA damage requires NF-kappa B

Although the transcription factor NF-κB is most clearly linked to the inhibition of extrinsic apoptotic signals such as TNFα by upregulating known anti-apoptotic genes, NF-κB has also been proposed to be required for p53-induced apoptosis in transformed cells. However, the involvement of NF-κB in this process is poorly understood. Here we investigate this mechanism and show that in transformed MEFs lacking NF-κB (p65-null cells) genotoxin-induced cytochrome c release is compromised. To further address how NF-κB contributes to apoptosis, gene profiling by microarray analysis of MEFs was performed, revealing that NF-κB is required for expression of Noxa, a pro-apoptotic BH3-only protein that is induced by genotoxins and that triggers cytochrome c release. Moreover, we find that in the absence of NF-κB, genotoxin treatment cannot induce Noxa mRNA expression. Noxa expression had been shown to be regulated directly by genes of the p53 family, like p73 and p63, following genotoxin treatment. Here we show that p73 is activated after genotoxin treatment only in the presence of NF-κB and that p73 induces Noxa gene expression through the p53 element in the promoter. Together our data provides an explanation for how loss of NF-κB abrogates genotoxin-induced apoptosis

Solar Oscillations and Convection: II. Excitation of Radial Oscillations

Solar p-mode oscillations are excited by the work of stochastic, non-adiabatic, pressure fluctuations on the compressive modes. We evaluate the expression for the radial mode excitation rate derived by Nordlund and Stein (Paper I) using numerical simulations of near surface solar convection. We first apply this expression to the three radial modes of the simulation and obtain good agreement between the predicted excitation rate and the actual mode damping rates as determined from their energies and the widths of their resolved spectral profiles. We then apply this expression for the mode excitation rate to the solar modes and obtain excellent agreement with the low l damping rates determined from GOLF data. Excitation occurs close to the surface, mainly in the intergranular lanes and near the boundaries of granules (where turbulence and radiative cooling are large). The non-adiabatic pressure fluctuations near the surface are produced by small instantaneous local imbalances between the divergence of the radiative and convective fluxes near the solar surface. Below the surface, the non-adiabatic pressure fluctuations are produced primarily by turbulent pressure fluctuations (Reynolds stresses). The frequency dependence of the mode excitation is due to effects of the mode structure and the pressure fluctuation spectrum. Excitation is small at low frequencies due to mode properties -- the mode compression decreases and the mode mass increases at low frequency. Excitation is small at high frequencies due to the pressure fluctuation spectrum -- pressure fluctuations become small at high frequencies because they are due to convection which is a long time scale phenomena compared to the dominant p-mode periods.Comment: Accepted for publication in ApJ (scheduled for Dec 10, 2000 issue). 17 pages, 27 figures, some with reduced resolution -- high resolution versions available at http://www.astro.ku.dk/~aake/astro-ph/0008048

A Search for Propylene Oxide and Glycine in Sagittarius B2 (LMH) and Orion

We have used the Mopra Telescope to search for glycine and the simple chiral molecule propylene oxide in the Sgr B2 (LMH) and Orion KL, in the 3-mm band. We have not detected either species, but have been able to put sensitive upper limits on the abundances of both molecules. The 3-sigma upper limits derived for glycine conformer I are 3.7 x 10^{14} cm^{-2} in both Orion-KL and Sgr B2 (LMH), comparable to the reported detections of conformer I by Kuan et al. However, as our values are 3-sigma upper limits rather than detections we conclude that this weighs against confirming the detection of Kuan et al. We find upper limits for the glycine II column density of 7.7 x 10^{12} cm^{-2} in both Orion-KL and Sgr B2 (LMH), in agreement with the results of Combes et al. The results presented here show that glycine conformer II is not present in the extended gas at the levels detected by Kuan et al. for conformer I. Our ATCA results (Jones et al.) have ruled out the detection of glycine (both conformers I and II) in the compact hot core of the LMH at the levels reported, so we conclude that it is unlikely that Kuan et al. have detected glycine in either Sgr B2 or Orion-KL. We find upper limits for propylene oxide abundance of 3.0 x 10^{14} cm^{-2} in Orion-KL and 6.7 x 10^{14} cm^{-2} in Sgr B2 (LMH). We have detected fourteen features in Sgr B2 and four features in Orion-KL which have not previously been reported in the ISM, but have not be able to plausibly assign these transitions to any carrier.Comment: 12 pages, 3 figures. Accepted by MNRAS 12th January 200

Probing the Circumgalactic Medium at High-Redshift Using Composite BOSS Spectra of Strong Lyman-alpha Forest Absorbers

We present composite spectra constructed from a sample of 242,150 Lyman-alpha (Lya) forest absorbers at redshifts 2.4<z<3.1 identified in quasar spectra from the Baryon Oscillation Spectroscopic Survey (BOSS) as part of Data Release 9 of the Sloan Digital Sky Survey III. We select forest absorbers by their flux in bins 138 km/s wide (approximately the size of the BOSS resolution element). We split these absorbers into five samples spanning the range of flux -0.05 < F<0.45. Tests on a smaller sample of high-resolution spectra show that our three strongest absorption bins would probe circumgalactic regions (projected separation < 300 proper kpc and |Delta v| < 300km/s) in about 60% of cases for very high signal-to-noise ratio. Within this subset, weakening Lya absorption is associated with decreasing purity of circumgalactic selection once BOSS noise is included. Our weaker two Lya absorption samples are dominated by the intergalactic medium. We present composite spectra of these samples and a catalogue of measured absorption features from HI and 13 metal ionization species, all of which we make available to the community. We compare measurements of seven Lyman series transitions in our composite spectra to single line models and obtain further constraints from their associated excess Lyman limit opacity. This analysis provides results consistent with column densities over the range 14.4 <~ Log (N_HI) <~ 16.45. We compare our measurements of metal absorption to a variety of simple single-line, single-phase models for a preliminary interpretation. Our results imply clumping on scales down to ~30 pc and near-solar metallicities in the circumgalactic samples, while high-ionization metal absorption consistent with typical IGM densities and metallicities is visible in all samples.Comment: 23 pages, 15 figures, 5 tables, link to downloadable data included. Accepted by MNRAS 2014 March 20. New sections 3.4 and 6.1 limiting the occurrence and impact of Lyman limit system

TSC22 in mammary gland development and breast cancer

Mammary gland involution is characterised by a high degree of apoptosis. By identifying genes that are upregulated at this developmental stage, we aimed to discover key factors that are involved in the induction of mammary epithelial cell death and therefore present potential tumour suppressors for breast cancer. Among 96 genes recently identified as specifically upregulated early during involution were the transforming growth factor beta (TGFβ)-stimulated clone 22 homologue (TSC-22/TGFβ1-induced transcript 4) and TGFβ3 [1]. TGFβ3 has recently been shown to be necessary for induction of apoptosis during mammary gland involution, while TSC-22 overexpression can lead to cell death. We have therefore tested whether TSC-22 mRNA expression can be induced by TGFβ3 and whether it is involved in or necessary for TGFβ-induced apoptosis. We further show that TSC-22 can enhance TGFβ3-induced Smad response and epithelial cell death. In addition, overexpression of TSC-22 alone can induce a Smad response and apoptosis in mammary epithelial cell cultures, which is independent of p53. Further, we have performed tests to study the necessity for Smad proteins during TSC-22-induced apoptosis, and to establish the intracellular localisation of TSC-22. A pilot study on a small cohort of archival breast cancer cases, representing all stages of malignant progression, shows that TSC-22 protein was reduced or undetectable in 60% of breast carcinomas when compared with adjacent normal breast tissue, suggesting that TSC-22 could indeed be a potential novel tumour suppressor gene. We shall present data showing that methylation of the TSC-22 promoter is not involved in the reduction of TSC-22 protein in breast cancer

The neutral hydrogen cosmological mass density at z = 5

We present the largest homogeneous survey of z > 4.4 damped Lyα systems (DLAs) using the spectra of 163 QSOs that comprise the Giant Gemini GMOS (GGG) survey. With this survey we make the most precise high-redshift measurement of the cosmological mass density of neutral hydrogen, ΩHi. At such high redshift, important systematic uncertainties in the identification of DLAs are produced by strong intergalactic medium absorption and QSO continuum placement. These can cause spurious DLA detections, result in real DLAs being missed or bias the inferred DLA column density distribution. We correct for these effects using a combination of mock and higher resolution spectra, and show that for the GGG DLA sample the uncertainties introduced are smaller than the statistical errors on ΩHi. We find ΩHI=0.98+0.20−0.18×10−3 at 〈z〉 = 4.9, assuming a 20 per cent contribution from lower column density systems below the DLA threshold. By comparing to literature measurements at lower redshifts, we show that ΩHi can be described by the functional form ΩHI(z)∝(1+z)0.4. This gradual decrease from z = 5 to 0 is consistent with the bulk of H I gas being a transitory phase fuelling star formation, which is continually replenished by more highly ionized gas from the intergalactic medium and from recycled galactic winds