Meromorphic Approximants to Complex Cauchy Transforms with Polar Singularities

We study AAK-type meromorphic approximants to functions $F$, where $F$ is a sum of a rational function $R$ and a Cauchy transform of a complex measure $\lambda$ with compact regular support included in $(-1,1)$, whose argument has bounded variation on the support. The approximation is understood in $L^p$-norm of the unit circle, $p\geq2$. We obtain that the counting measures of poles of the approximants converge to the Green equilibrium distribution on the support of $\lambda$ relative to the unit disk, that the approximants themselves converge in capacity to $F$, and that the poles of $R$ attract at least as many poles of the approximants as their multiplicity and not much more.Comment: 39 pages, 4 figure

The interdependence of behavioral and somatic health: implications for conceptualizing health and measuring treatment outcomes

<b>Purpose:</b> The interdependence of behavioral and somatic aspects of various health conditions warrants greater emphasis on an integrated care approach.<br><br> <b>Theory:</b> We propose that integrated approaches to health and wellness require comprehensive and empirically-valid outcome measures to assess quality of care.<br><br> <b>Method:</b> We discuss the transition from independent to integrated treatment approaches and provide examples of new systems for integrated assessment of treatment outcome.<br><br> <b>Results:</b> Evidence suggests that support for an independent treatment approach is waning and momentum is building towards more integrated care. In addition, research evidence suggests integrated care improves health outcomes, and both physicians and patients have favorable impressions of integrated care.<br><br> <b>Conclusions:</b> As treatment goals in the integrated perspective expand to take into account the intimate relationships among mental illness, overall health, and quality of life, clinicians need to develop outcome measures that are similarly comprehensive. Discussion: Increased recognition, by researchers, providers, and insurers, of the interdependence between behavioral and physical health holds great promise for innovative treatments that could significantly improve patients' lives

The relationship between structural game characteristics and gambling behavior: a population-level study

The aim of this study was to examine the relationship between the structural characteristics and gambling behavior among video lottery terminal (VLT) gamblers. The study was ecological valid, because the data consisted of actual gambling behavior registered in the participants natural gambling environment without intrusion by researchers. Online behavioral tracking data from Multix, an eight game video lottery terminal, were supplied by Norsk-Tipping (the state owned gambling company in Norway). The sample comprised the entire population of Multix gamblers (N = 31,109) who had gambled in January 2010. The individual number of bets made across games was defined as the dependent variable, reward characteristics of a game (i.e., payback percentage, hit frequency, size of winnings and size of jackpot) and bet characteristics of a game (i.e., range of betting options and availability of advanced betting options) served as the independent variables. Control variables were age and gender. Two separate cross-classified multilevel random intercepts models were used to analyze the relationship between bets made, reward characteristics and bet characteristics, where the number of bets was nested within both individuals and within games. The results show that the number of bets is positively associated with payback percentage, hit frequency, being female and age, and negatively associated with size of wins and range of available betting options. In summary, the results show that the reward characteristics and betting options explained 27 % and 15 % of the variance in the number of bets made, respectively. It is concluded that structural game characteristics affect gambling behavior. Implications of responsible gambling are discussed

NOXA as critical mediator for drug combinations in polychemotherapy

During polychemotherapy, cytotoxic drugs are given in combinations to enhance their anti-tumor effectiveness. For most drug combinations, underlying signaling mechanisms responsible for positive drug–drug interactions remain elusive. Here, we prove a decisive role for the Bcl-2 family member NOXA to mediate cell death by certain drug combinations, even if drugs were combined which acted independently from NOXA, when given alone. In proof-of-principle studies, betulinic acid, doxorubicin and vincristine induced cell death in a p53- and NOXA-independent pathway involving mitochondrial pore formation, release of cytochrome c and caspase activation. In contrast, when betulinic acid was combined with either doxorubicine or vincristine, cell death signaling changed considerably; the drug combinations clearly depended on both p53 and NOXA. Similarly and of high clinical relevance, in patient-derived childhood acute leukemia samples the drug combinations, but not the single drugs depended on p53 and NOXA, as shown by RNA interference studies in patient-derived cells. Our data emphasize that NOXA represents an important target molecule for combinations of drugs that alone do not target NOXA. NOXA might have a special role in regulating apoptosis sensitivity in the complex interplay of polychemotherapy. Deciphering the differences in signaling of single drugs and drug combinations might enable designing highly effective novel polychemotherapy regimens

Serum vitamin D levels and survival of patients with colorectal cancer: Post-hoc analysis of a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Recently, serum 25-hydroxyvitamin D (25OHD) levels were shown to be associated with the survival of patients with colorectal cancer. However, 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels. In this study, we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer.</p> <p>Methods</p> <p>We started a prospective cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum samples and clinical data. As part of a post-hoc analysis, serum 25OHD levels were measured by radioimmunoassay. Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis, gender, cancer stage, residual tumor after surgery, time period of surgery, location of tumor, adjuvant chemotherapy and number of lymph nodes with metastasis at surgery. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were determined.</p> <p>Results</p> <p>Serum 25OHD levels were measured in 257 patients. Only 3% had sufficient levels (30 ng/ml and greater). Based on month of blood sampling, an annual oscillation of 25OHD levels was seen, with levels being lower in spring and higher in late summer. Higher 25OHD levels were associated with better overall survival under multi-variate analysis (HR, 0.91: 95% CI, 0.84 to 0.99, <it>P </it>= 0.027).</p> <p>Conclusions</p> <p>These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer.</p

Identification of the Inorganic Pyrophosphate Metabolizing, ATP Substituting Pathway in Mammalian Spermatozoa

Inorganic pyrophosphate (PPi) is generated by ATP hydrolysis in the cells and also present in extracellular matrix, cartilage and bodily fluids. Fueling an alternative pathway for energy production in cells, PPi is hydrolyzed by inorganic pyrophosphatase (PPA1) in a highly exergonic reaction that can under certain conditions substitute for ATP-derived energy. Recombinant PPA1 is used for energy-regeneration in the cell-free systems used to study the zymology of ATP-dependent ubiquitin-proteasome system, including the role of sperm-borne proteasomes in mammalian fertilization. Inspired by an observation of reduced in vitro fertilization (IVF) rates in the presence of external, recombinant PPA1, this study reveals, for the first time, the presence of PPi, PPA1 and PPi transporter, progressive ankylosis protein ANKH in mammalian spermatozoa. Addition of PPi during porcine IVF increased fertilization rates significantly and in a dose-dependent manner. Fluorometric assay detected high levels of PPi in porcine seminal plasma, oviductal fluid and spermatozoa. Immunofluorescence detected PPA1 in the postacrosomal sheath (PAS) and connecting piece of boar spermatozoa; ANKH was present in the sperm head PAS and equatorial segment. Both ANKH and PPA1 were also detected in human and mouse spermatozoa, and in porcine spermatids. Higher proteasomal-proteolytic activity, indispensable for fertilization, was measured in spermatozoa preserved with PPi. The identification of an alternative, PPi dependent pathway for ATP production in spermatozoa elevates our understanding of sperm physiology and sets the stage for the improvement of semen extenders, storage media and IVF media for animal biotechnology and human assisted reproductive therapies

Instabilities in the wake of an inclined prolate spheroid

We investigate the instabilities, bifurcations and transition in the wake behind a 45-degree inclined 6:1 prolate spheroid, through a series of direct numerical simulations (DNS) over a wide range of Reynolds numbers (Re) from 10 to 3000. We provide a detailed picture of how the originally symmetric and steady laminar wake at low Re gradually looses its symmetry and turns unsteady as Re is gradually increased. Several fascinating flow features have first been revealed and subsequently analysed, e.g. an asymmetric time-averaged flow field, a surprisingly strong side force etc. As the wake partially becomes turbulent, we investigate a dominating coherent wake structure, namely a helical vortex tube, inside of which a helical symmetry alteration scenario was recovered in the intermediate wake, together with self-similarity in the far wake.Comment: Book chapter in "Computational Modeling of Bifurcations and Instabilities in Fluid Dynamics (A. Gelfgat ed.)", Springe

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p&nbsp;&lt;.001. Over 24&nbsp;months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10&nbsp;ml/min/1.73&nbsp;m2 decrease), that was most notable in patients with eGFR &lt;30&nbsp;ml/min/1.73&nbsp;m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90&nbsp;ml/min/1.73&nbsp;m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients