Change in Physiological Variables in the Last Two Weeks of Life: An Observational Study of Hospitalized Adults With Heart Failure

Context Recognition of dying is a difficult task in end-stage heart failure, yet it remains an important clinical skill in providing good palliative care to these patients. Objectives To use routinely collected data to explore evidence for physiological change in the final two weeks of life in end-stage heart failure. Methods This was a retrospective cohort study of routinely collected data from hospital inpatients dying as a result of heart failure during a one-year period in a U.K. hospital. Data were analyzed using descriptive techniques and multilevel modeling. Results Results were obtained on 81 patients. Respiratory function (evidenced by falling oxygen saturation and rising respiratory rate) deteriorated by a clinically significant amount in the final two weeks of life (P < 0.001). Renal function (evidenced by rising serum urea and creatinine) also demonstrated a clinically significant deterioration over the same period (P < 0.001 and P = 0.005, respectively). Serum albumin fell over a period of months (P < 0.001). Heart rate and blood pressure did not demonstrate clinically significant change over the same period. Conclusions Deteriorating respiratory and renal function may indicate imminent dying in heart failure. A fall in serum albumin may signify poor prognosis over a timescale of weeks to months. Conversely, hemodynamic parameters may remain relatively stable in the final days of life and should not be reassuring in end-stage heart failure patients

Baseline functioning and stress reactivity in maltreating parents and at-risk adults: Review and meta-analyses of autonomic nervous system studies

Development Psychopathology in context: famil

The Evolution of Sunspot Magnetic Fields Associated with a Solar Flare

Solar flares occur due to the sudden release of energy stored in active-region magnetic fields. To date, the pre-cursors to flaring are still not fully understood, although there is evidence that flaring is related to changes in the topology or complexity of an active region's magnetic field. Here, the evolution of the magnetic field in active region NOAA 10953 was examined using Hinode/SOT-SP data, over a period of 12 hours leading up to and after a GOES B1.0 flare. A number of magnetic-field properties and low-order aspects of magnetic-field topology were extracted from two flux regions that exhibited increased Ca II H emission during the flare. Pre-flare increases in vertical field strength, vertical current density, and inclination angle of ~ 8degrees towards the vertical were observed in flux elements surrounding the primary sunspot. The vertical field strength and current density subsequently decreased in the post-flare state, with the inclination becoming more horizontal by ~7degrees. This behaviour of the field vector may provide a physical basis for future flare forecasting efforts.Comment: Accepted for Publication in Solar Physics. 16 pages, 4 figure

Helioseismology of Sunspots: A Case Study of NOAA Region 9787

Various methods of helioseismology are used to study the subsurface properties of the sunspot in NOAA Active Region 9787. This sunspot was chosen because it is axisymmetric, shows little evolution during 20-28 January 2002, and was observed continuously by the MDI/SOHO instrument. (...) Wave travel times and mode frequencies are affected by the sunspot. In most cases, wave packets that propagate through the sunspot have reduced travel times. At short travel distances, however, the sign of the travel-time shifts appears to depend sensitively on how the data are processed and, in particular, on filtering in frequency-wavenumber space. We carry out two linear inversions for wave speed: one using travel-times and phase-speed filters and the other one using mode frequencies from ring analysis. These two inversions give subsurface wave-speed profiles with opposite signs and different amplitudes. (...) From this study of AR9787, we conclude that we are currently unable to provide a unified description of the subsurface structure and dynamics of the sunspot.Comment: 28 pages, 18 figure

Modeling the Subsurface Structure of Sunspots

While sunspots are easily observed at the solar surface, determining their subsurface structure is not trivial. There are two main hypotheses for the subsurface structure of sunspots: the monolithic model and the cluster model. Local helioseismology is the only means by which we can investigate subphotospheric structure. However, as current linear inversion techniques do not yet allow helioseismology to probe the internal structure with sufficient confidence to distinguish between the monolith and cluster models, the development of physically realistic sunspot models are a priority for helioseismologists. This is because they are not only important indicators of the variety of physical effects that may influence helioseismic inferences in active regions, but they also enable detailed assessments of the validity of helioseismic interpretations through numerical forward modeling. In this paper, we provide a critical review of the existing sunspot models and an overview of numerical methods employed to model wave propagation through model sunspots. We then carry out an helioseismic analysis of the sunspot in Active Region 9787 and address the serious inconsistencies uncovered by \citeauthor{gizonetal2009}~(\citeyear{gizonetal2009,gizonetal2009a}). We find that this sunspot is most probably associated with a shallow, positive wave-speed perturbation (unlike the traditional two-layer model) and that travel-time measurements are consistent with a horizontal outflow in the surrounding moat.Comment: 73 pages, 19 figures, accepted by Solar Physic

B cell activity is impaired in human and mouse obesity and is responsive to an essential fatty acid upon murine influenza infection

Obesity is associated with increased risk for infections and poor responses to vaccinations, which may be due to compromised B cell function. However, there is limited information about the influence of obesity on B cell function and underlying factors that modulate B cell responses. Therefore, we studied B cell cytokine secretion and/or Ab production across obesity models. In obese humans, B cell IL-6 secretion was lowered and IgM levels were elevated upon ex vivo anti-BCR/TLR9 stimulation. In murine obesity induced by a high fat diet, ex vivo IgM and IgG were elevated with unstimulated B cells. Furthermore, the high fat diet lowered bone marrow B cell frequency accompanied by diminished transcripts of early lymphoid commitment markers. Murine B cell responses were subsequently investigated upon influenza A/Puerto Rico/8/34 infection using a Western diet model in the absence or presence of docosahexaenoic acid (DHA). DHA, an essential fatty acid with immunomodulatory properties, was tested because its plasma levels are lowered in obesity. Relative to controls, mice consuming theWestern diet had diminished Ab titers whereas theWestern diet plus DHA improved titers. Mechanistically, DHA did not directly target B cells to elevate Ab levels. Instead, DHA increased the concentration of the downstream specialized proresolving lipid mediators (SPMs) 14-hydroxydocosahexaenoic acid, 17-hydroxydocosahexaenoic acid, and protectin DX. All three SPMs were found to be effective in elevating murine Ab levels upon influenza infection. Collectively, the results demonstrate that B cell responses are impaired across human and mouse obesity models and show that essential fatty acid status is a factor influencing humoral immunity, potentially through an SPM-mediated mechanism

Large-eddy simulation of low-frequency unsteadiness in a turbulent shock-induced separation bubble

The need for better understanding of the low-frequency unsteadiness observed in shock wave/turbulent boundary layer interactions has been driving research in this area for several decades. We present here a large-eddy simulation investigation of the interaction between an impinging oblique shock and a Mach 2.3 turbulent boundary layer. Contrary to past large-eddy simulation investigations on shock/turbulent boundary layer interactions, we have used an inflow technique which does not introduce any energetically significant low frequencies into the domain, hence avoiding possible interference with the shock/boundary layer interaction system. The large-eddy simulation has been run for much longer times than previous computational studies making a Fourier analysis of the low frequency possible. The broadband and energetic low-frequency component found in the interaction is in excellent agreement with the experimental findings. Furthermore, a linear stability analysis of the mean flow was performed and a stationary unstable global mode was found. The long-run large-eddy simulation data were analyzed and a phase change in the wall pressure fluctuations was related to the global-mode structure, leading to a possible driving mechanism for the observed low-frequency motions

Interaction of inflammatory cytokines and erythropoeitin in iron metabolism and erythropoiesis in anaemia of chronic disease

In chronic inflammatory conditions increased endogenous release of specific cytokines (TNFα, IL-1, IL-6, IFNγ and others) is presumed. It has been shown that those of monocyte lineage play a key role in cytokine expression and synthesis. This may be associated with changes in iron metabolism and impaired erythropoiesis and may lead to development of anaemia in patients with rheumatoid arthritis. Firstly, increased synthesis of acute phase proteins, like ferritin, during chronic inflammation is proposed as the way by which the toxic effect of iron and thereby the synthesis of free oxy-radicals causing the damage on the affected joints, may be reduced. This is associated with a shift of iron towards the mononuclear phagocyte system which may participate in the development of anaemia of chronic disease. Secondly, an inhibitory action of inflammatory cytokines (TNFα, IL-1), on proliferation and differentiation of erythroid progenitors as well as on synthesis of erythropoietin has been shown, thereby also contributing to anaemia. Finally, chronic inflammation causes multiple, complex disturbances in the delicate physiologic equilibrium of interaction between cytokines and cells (erythroid progenitors, cells of mononuclear phagocyte system and erythropoietin producing cells) leading to development of anaemia of chronic disease (Fig. 1)

Surface-focused Seismic Holography of Sunspots: I. Observations

We present a comprehensive set of observations of the interaction of p-mode oscillations with sunspots using surface-focused seismic holography. Maps of travel-time shifts, relative to quiet-Sun travel times, are shown for incoming and outgoing p modes as well as their mean and difference. We compare results using phase-speed filters with results obtained with filters that isolate single p-mode ridges, and further divide the data into multiple temporal frequency bandpasses. The f mode is removed from the data. The variations of the resulting travel-time shifts with magnetic-field strength and with the filter parameters are explored. We find that spatial averages of these shifts within sunspot umbrae, penumbrae, and surrounding plage often show strong frequency variations at fixed phase speed. In addition, we find that positive values of the mean and difference travel-time shifts appear exclusively in waves observed with phase-speed filters that are dominated by power in the low-frequency wing of the p1 ridge. We assess the ratio of incoming to outgoing p-mode power using the ridge filters and compare surface-focused holography measurements with the results of earlier published p-mode scattering measurements using Fourier-Hankel decomposition.Comment: Solar Physics, accepte

AD51B in Familial Breast Cancer

Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C&gt;T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11–1.19, P = 8.88 x 10−16) and among familial cases (OR: 1.24, 95% CI: 1.16–1.32, P = 6.19 x 10−11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk