Integrating Lean Six Sigma and discrete-event simulation for shortening the appointment lead-time in gynecobstetrics departments: a case study

Long waiting time to appointment may be a worry for pregnant women, particularly those who need perinatology consultation since it could increase anxiety and, in a worst case scenario, lead to an increase in fetal, infant, and maternal mortality. Treatment costs may also increase since pregnant women with diverse pathologies can develop more severe complications. As a step towards improving this process, we propose a methodological approach to reduce the appointment lead-time in outpatient gynecobstetrics departments. This framework involves combining the Six Sigma method to identify defects in the appointment scheduling process with a discrete-event simulation (DES) to evaluate the potential success of removing such defects in simulation before we resort to changing the real-world healthcare system. To do these, we initially characterize the gynecobstetrics department using a SIPOC diagram. Then, six sigma performance metrics are calculated to evaluate how well the department meets the government target in relation to the appointment lead-time. Afterwards, a cause-and-effect analysis is undertaken to identify potential causes of appointment lead-time variation. These causes are later validated through ANOVA, regression analysis, and DES. Improvement scenarios are next designed and pretested through computer simulation models. Finally, control plans are deployed to maintain the results achieved through the implementation of the DES-Six sigma approach. The aforementioned framework was validated in a public gynecobstetrics outpatient department. The results revealed that mean waiting time decreased from 6.9 days to 4.1 days while variance passed from 2.46 days2 to 1.53 days2

Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure.

BackgroundIntra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well-established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole.MethodsPregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment.ResultsIntra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury.ConclusionsIntra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2^ndEGFR-TKI administration.</p> <p>Methods</p> <p>We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.</p> <p>Results</p> <p>Three patients (27%) were treated with gefitinib as the 2^ndEGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2^ndEGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2^ndEGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2^ndEGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.</p> <p>Conclusions</p> <p>Our results indicate that a 2^ndEGFR-TKI treatment can be an effective treatment option for gefitinib responders.</p

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2^ndEGFR-TKI administration.</p> <p>Methods</p> <p>We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.</p> <p>Results</p> <p>Three patients (27%) were treated with gefitinib as the 2^ndEGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2^ndEGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2^ndEGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2^ndEGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.</p> <p>Conclusions</p> <p>Our results indicate that a 2^ndEGFR-TKI treatment can be an effective treatment option for gefitinib responders.</p

Hard Superconductivity of a Soft Metal in the Quantum Regime

Superconductivity is inevitably suppressed in reduced dimensionality. Questions of how thin superconducting wires or films can be before they lose their superconducting properties have important technological ramifications and go to the heart of understanding coherence and robustness of the superconducting state in quantum-confined geometries. Here, we exploit quantum confinement of itinerant electrons in a soft metal to stabilize superconductors with lateral dimensions of the order of a few millimeters and vertical dimensions of only a few atomic layers. These extremely thin superconductors show no indication of defect- or fluctuation-driven suppression of superconductivity and sustain supercurrents of up to 10% of the depairing current density. The extreme hardness of the critical state is attributed to quantum trapping of vortices. This study paints a conceptually appealing, elegant picture of a model nanoscale superconductor with calculable critical state properties. It indicates the intriguing possibility of exploiting robust superconductivity at the nanoscale.Comment: 15 pages, 4 figures, submitted to Nature Physic

Improved Measurement of the Pseudoscalar Decay Constant fDsf_{D_{s}}

We present a new determination of the Ds decay constant, f_{Ds} using 5 million continuum charm events obtained with the CLEO II detector. Our value is derived from our new measured ratio of widths for Ds -> mu nu/Ds -> phi pi of 0.173+/- 0.021 +/- 0.031. Taking the branching ratio for Ds -> phi pi as (3.6 +/- 0.9)% from the PDG, we extract f_{Ds} = (280 +/- 17 +/- 25 +/- 34){MeV}. We compare this result with various model calculations.Comment: 23 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

First Observation of τ→3πηντ\tau\to 3\pi\eta\nu_{\tau} and τ→f1πντ\tau\to f_{1}\pi\nu_{\tau} Decays

We have observed new channels for $\tau$ decays with an $\eta$ in the final state. We study 3-prong tau decays, using the $\eta\to\gamma\gamma$ and \eta\to 3\piz decay modes and 1-prong decays with two \piz's using the $\eta\to\gamma\gamma$ channel. The measured branching fractions are \B(\tau^{-}\to \pi^{-}\pi^{-}\pi^{+}\eta\nu_{\tau}) =(3.4^{+0.6}_{-0.5}\pm0.6)\times10^{-4} and \B(\tau^{-}\to \pi^{-}2\piz\eta\nu_{\tau} =(1.4\pm0.6\pm0.3)\times10^{-4}. We observe clear evidence for $f_1\to\eta\pi\pi$ substructure and measure \B(\tau^{-}\to f_1\pi^{-}\nu_{\tau})=(5.8^{+1.4}_{-1.3}\pm1.8)\times10^{-4}. We have also searched for $\eta'(958)$ production and obtain 90% CL upper limits \B(\tau^{-}\to \pi^{-}\eta'\nu_\tau)<7.4\times10^{-5} and \B(\tau^{-}\to \pi^{-}\piz\eta'\nu_\tau)<8.0\times10^{-5}.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Search for the Decays B^0 -> D^{(*)+} D^{(*)-}

Using the CLEO-II data set we have searched for the Cabibbo-suppressed decays B^0 -> D^{(*)+} D^{(*)-}. For the decay B^0 -> D^{*+} D^{*-}, we observe one candidate signal event, with an expected background of 0.022 +/- 0.011 events. This yield corresponds to a branching fraction of Br(B^0 -> D^{*+} D^{*-}) = (5.3^{+7.1}_{-3.7}(stat) +/- 1.0(syst)) x 10^{-4} and an upper limit of Br(B^0 -> D^{*+} D^{*-}) D^{*\pm} D^\mp and B^0 -> D^+ D^-, no significant excess of signal above the expected background level is seen, and we calculate the 90% CL upper limits on the branching fractions to be Br(B^0 -> D^{*\pm} D^\mp) D^+ D^-) < 1.2 x 10^{-3}.Comment: 12 page postscript file also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review Letter

ΛΛˉ\Lambda\bar{\Lambda} Production in Two-Photon Interactions at CLEO

Using the CLEO detector at the Cornell $e^+e^-$ storage ring, CESR, we study the two-photon production of $\Lambda \bar{\Lambda}$, making the first observation of $\gamma \gamma \to \Lambda \bar{\Lambda}$. We present the cross-section for $\gamma \gamma \to \Lambda \bar{\Lambda}$ as a function of the $\gamma \gamma$ center of mass energy and compare it to that predicted by the quark-diquark model.Comment: 10 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN