Moderately Preterm Infants : studies on Length of Hospital Stay and Neonatal Outcome

Objective Moderately preterm infants account for a large proportion of admissions and bed-days in neonatal units. Determinants of length of hospital stay, contemporary measures of morbidity by gestational week and risk factors predicting neonatal morbidity have been poorly studied. The overall purpose of this thesis was to fill these gaps with knowledge to make neonatal care more effective, and to improve short- and long-term outcome for moderately preterm infants. Methods Observational studies on length of hospital stay for moderately preterm infants in a longitudinal perspective over 20 years (Paper I) and a cross-sectional multicenter survey (Paper II) were performed. Risk factors for prolonged length of stay were determined in Paper II. Neonatal outcomes were studied in two national populationbased studies. Paper III explored neonatal morbidity and interventions stratified by gestational week. In Paper IV, rates of transient tachypnea of the newborn (TTN) and respiratory distress syndrome (RDS) among moderately preterm infants were compared to corresponding rates in late preterm to term infants, and risk factors for these acute respiratory morbidities were evaluated. Results Paper I found that length of stay decreased by an average of 14 days from 1983 to 2002, in spite of no concomitant decrease in neonatal morbidity. Paper II showed that only 13% of the variation in length of stay in Swedish neonatal units (which differed up to two weeks) could be attributed to neonatal morbidity. In Paper III, overall rates of common neonatal morbidities were found to vary between 15 and 59% in moderately preterm infants, with a strong inverse relation to birth weight standard deviation score and gestational age at birth. Paper IV demonstrated that besides low gestational age, Cesarean section, male sex and low Apgar score are associated to significantly increased risks for TTN and RDS in moderately preterm infants. Conclusions Whereas neonatal morbidity has remained essentially unchanged and high, length of hospital stay has decreased significantly for moderately preterm infants during the last 20 years. Our data suggest that organizational factors of neonatal care are responsible for this development. Moderately preterm infants continue to face a considerable risk of acute respiratory morbidity, which is also predicted by low gestational age, multiparity, Cesarean section, low Apgar score and male sex

Hanbury Brown-Twiss Interferometry for Fractional and Integer Mott Phases

Hanbury-Brown-Twiss interferometry (HBTI) is used to study integer and fractionally filled Mott Insulator (MI) phases in period-2 optical superlattices. In contrast to the quasimomentum distribution, this second order interferometry pattern exhibits high contrast fringes in the it insulating phases. Our detailed study of HBTI suggests that this interference pattern signals the various superfluid-insulator transitions and therefore can be used as a practical method to determine the phase diagram of the system. We find that in the presence of a confining potential the insulating phases become robust as they exist for a finite range of atom numbers. Furthermore, we show that in the trapped case the HBTI interferogram signals the formation of the MI domains and probes the shell structure of the system.Comment: 13 pages, 15 figure

Noise Correlations of Hard-core Bosons: Quantum Coherence and Symmetry Breaking

Noise correlations, such as those observable in the time of flight images of a released cloud, are calculated for hard-core bosonic (HCB) atoms. We find that the standard mapping of HCB systems onto spin-1/2 XY models fails in application to computation of noise correlations due to the contribution of multiply occupied virtual states in HCB systems. Such states do not exist in spin models. An interesting manifestation of such states is the breaking of particle-hole symmetry in HCB. We use noise correlations to explore quantum coherence of strongly correlated bosons in the fermionized regime with and without external parabolic confinement. Our analysis points to distinctive new experimental signatures of the Mott phase.Comment: 17 pages, 6 figures. This is a detailed revised version of quant-ph/0507153. It has been submitted to Journal of Physics B: the special edition for the Cortona BEC worksho

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

<p>Abstract</p> <p>Background</p> <p>High concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro.</p> <p>Methods</p> <p>Lag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 μg/ml, 2.6 μg/ml, 0.5 μg/ml, 0.25 μg/ml, and 0.125 μg/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM).</p> <p>Results</p> <p/> <p>In PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCo→_{35 min}were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→_{35 min}with no effect on PTG but were independent of rFVIIa concentration.</p> <p>Conclusion</p> <p/> <p>Low concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications.</p

Thrombin generation by activated factor VII on platelet activated by different agonists. Extending the cell-based model of hemostasis

BACKGROUND: Platelet activation is crucial in normal hemostasis. Using a clotting system free of external tissue factor, we investigated whether activated Factor VII in combination with platelet agonists increased thrombin generation (TG) in vitro. METHODS AND RESULTS: TG was quantified by time parameters: lag time (LT) and time to peak (TTP), and by amount of TG: peak of TG (PTG) and area under thrombin formation curve after 35 minutes (AUC→(35min)) in plasma from 29 healthy volunteers using the calibrated automated thrombography (CAT) technique. TG parameters were measured at basal conditions and after platelet stimulation by sodium arachidonate (AA), ADP, and collagen (Col). In addition, the effects of recombinant activated FVII (rFVIIa) alone or combined with the other platelet agonists on TG parameters were investigated. We found that LT and TTP were significantly decreased (p < 0.05) and PTG and AUC→(35min )were significantly increased (p < 0.05) in platelet rich plasma activated with AA, ADP, Col, and rFVIIa compared to non-activated platelet rich plasma from normal subjects (p = 0.01). Furthermore platelet rich plasma activated by the combined effects of rFVIIa plus AA, ADP or Col had significantly reduced LT and TTP and increased AUC→(35min )(but not PTG) when compared to platelet rich plasma activated with agonists in the absence of rFVIIa. CONCLUSION: Platelets activated by AA, ADP, Col or rFVIIa triggered TG. This effect was increased by combining rFVIIa with other agonists. Our intrinsic coagulation system produced a burst in TG independent of external tissue factor activity an apparent hemostatic effect with little thrombotic capacity. Thus we suggest a modification in the cell-based model of hemostasis

A life devoted to “the word”: The linguistic legacy of Albert and Lois Buckwalter in the Chaco evangelical project

Este artículo aborda el proyecto lingüístico del matrimonio de misionerosmenonitas formado por Albert Buckwalter y Lois Litwiller Buckwalter en elChaco argentino. Se basa en fuentes inéditas, en entrevistas personales a LoisL. Buckwalter y en publicaciones de ambos. La labor de la traducción de la Bibliaa los idiomas toba, mocoví y pilagá, así como también las decisiones en tornoa la elaboración de alfabetos, vocabularios y notas gramaticales, fueron consistentescon el saber lingüístico académico de la época y parte integral de suproyecto evangelizador. Dicha tarea se enmarca en el contexto de un cambiogeneral de paradigma vinculado al creciente rol de la antropología y la lingüísticaen la formación de los misioneros. El trabajo destaca también el aporte deltrabajo del matrimonio Buckwalter a la lingüística chaqueña actual.This article focuses on the linguistic project of the Mennonite missionary couple of Albert Buckwalter and Lois Litwiller Buckwalter in the Argentine Chaco. The analysis is based on unpublished sources as well as personal interviews with Lois L. Buckwalter and publications by both. The work of translating the Bible into the Toba, Mocoví and Pilagá languages as well as the decisions regarding the elaboration of alphabets, vocabularies and grammatical notes were consistent with the academic linguistic knowledge of the time, and an integral part of their evangelizing project. This task is framed in the context of a general paradigm shift linked to the growing role of anthropology and linguistics in the formation of missionaries. The study also highlights the contribution that the work of the Buckwalter couple represents for current Chaco linguistics.Fil: Altman, Agustina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Messineo, Maria Cristina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Departamento de Ciencias Antropológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Interventions for enhancing adherence with physiotherapy: a systematic review

Poor adherence to treatment is commonplace and may adversely affect outcomes, efficiency and healthcare cost. The aim of this systematic review was to identify strategies to improve adherence with musculoskeletal outpatient treatment. Five suitable studies were identified which provided moderate evidence that a motivational cognitive-behavioural programme can improve attendance at exercise-based clinic sessions. There was conflicting evidence that adherence interventions increase short-term adherence with exercise. There was strong evidence that adherence strategies are not effective at improving long-term adherence with home exercise. Due to the multi-dimensional nature of non-adherence, the strategies to improve adherence with physiotherapy treatment are likely to be broad in spectrum. Combined interventions may be effective at promoting adherence with clinic appointments and exercise, though further research would be required to confirm this. Further research to increase basic understanding of the factors which act as a barrier to adherence could facilitate development of strategies to overcome non-adherence

Impact of a 6-wk olive oil supplementation in healthy adults on urinary proteomic biomarkers of coronary artery disease, chronic kidney disease, and diabetes (types 1 and 2): a randomized, parallel, controlled, double-blind study

Background: Olive oil (OO) consumption is associated with cardiovascular disease prevention because of both its oleic acid and phenolic contents. The capacity of OO phenolics to protect against low-density lipoprotein (LDL) oxidation is the basis for a health claim by the European Food Safety Authority. Proteomic biomarkers enable an early, presymptomatic diagnosis of disease, which makes them important and effective, but understudied, tools for primary prevention. Objective: We evaluated the impact of supplementation with OO, either low or high in phenolics, on urinary proteomic biomarkers of coronary artery disease (CAD), chronic kidney disease (CKD), and diabetes. Design: Self-reported healthy participants (n = 69) were randomly allocated (stratified block random assignment) according to age and body mass index to supplementation with a daily 20-mL dose of OO either low or high in phenolics (18 compared with 286 mg caffeic acid equivalents per kg, respectively) for 6 wk. Urinary proteomic biomarkers were measured at baseline and 3 and 6 wk alongside blood lipids, the antioxidant capacity, and glycation markers. Results: The consumption of both OOs improved the proteomic CAD score at endpoint compared with baseline (mean improvement: –0.3 for low-phenolic OO and −0.2 for high-phenolic OO; P &#60; 0.01) but not CKD or diabetes proteomic biomarkers. However, there was no difference between groups for changes in proteomic biomarkers or any secondary outcomes including plasma triacylglycerols, oxidized LDL, and LDL cholesterol. Conclusion: In comparison with low-phenolic OO, supplementation for 6 wk with high-phenolic OO does not lead to an improvement in cardiovascular health markers in a healthy cohort. This trial was registered at www.controlled-trials.com as ISRCTN93136746

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro