Critical Dynamics of a Vortex Loop Model for the Superconducting Transition

We calculate analytically the dynamic critical exponent $z_{MC}$ measured in Monte Carlo simulations for a vortex loop model of the superconducting transition, and account for the simulation results. In the weak screening limit, where magnetic fluctuations are neglected, the dynamic exponent is found to be $z_{MC} = 3/2$. In the perfect screening limit, $z_{MC} = 5/2$. We relate $z_{MC}$ to the actual value of $z$ observable in experiments and find that $z \sim 2$, consistent with some experimental results

On-the-fly Uniformization of Time-Inhomogeneous Infinite Markov Population Models

This paper presents an on-the-fly uniformization technique for the analysis of time-inhomogeneous Markov population models. This technique is applicable to models with infinite state spaces and unbounded rates, which are, for instance, encountered in the realm of biochemical reaction networks. To deal with the infinite state space, we dynamically maintain a finite subset of the states where most of the probability mass is located. This approach yields an underapproximation of the original, infinite system. We present experimental results to show the applicability of our technique

Obstetric and Perinatal Outcomes in Type 1 Diabetic Pregnancies: A large, population-based study

The aim of this epidemiological study was to elucidate whether in recent years, obstetric and perinatal outcomes in pregnancies complicated by type 1 diabetes (T1DM) have improved or not. The objective was also to identify possible risk factors for adverse outcome for the mother, fetus and the newborn. All studies (Ι-ΙV) included in this thesis were based on national data from the Swedish Medical Birth Registry, during the time period 1991-2007. In 5,089 type 1 diabetic pregnancies and 1.2 million controls we found significantly increased risks of all adverse outcomes in women with T1DM: adjusted odds ratios: severe preeclampsia: 4.47 (3.77-5.31), Caesarean delivery: 5.31 (4.97-5.69), stillbirth: 3.34 (2.46- 4.55), perinatal mortality: 3.29 (2.50-4.33), major malformations: 2.50 (2.13-2.94) and large for gestational age: LGA (birth weight ≥ +2 SD): 11.45 (10.61-12.36) (study Ι). The markedly elevated odds of an LGA outcome inspired us to characterize in more detail the distribution of birth size in a large national cohort of T1DM offspring (study ΙΙ n=3,705) and to investigate if disproportionate body composition was associated with increased risk of perinatal complications (study ΙΙΙ n=3,517). Percentiles for birth weight (BW), birth length (BL) and head circumference (HC) were formed based on data from non-diabetic pregnancies and standard deviation scores (SDS) were calculated for BW, BL and HC. The ponderal index (PI: BW in grams/(BL in cm) ³ was used as a proxy for body proportionality and fat mass and we defined disproportionate/overweight LGA as infants with a BW and PI ≥90th percentile for gestational age and gender. The distributions of BW, BL and HC were all unimodal but significantly shifted to the right of the normal reference. The distribution for BW was most markedly shifted to the right. 47% were LGA with a BW ≥90th adjusted percentile. The mean ponderal index (PI) was significantly increased and 46% of LGA infants were disproportionate with a PI ≥90th percentile and thus overweight at birth. A novel and unexpected finding was that fetal macrosomia was more pronounced in preterm and female infants (study ΙΙ). Surprisingly, neonatal outcome was independent of body proportionality in appropriate for gestational age (AGA) and LGA infants. The risk of adverse outcome was significantly increased in LGA compared with AGA infants born at term (study ΙΙΙ). There was a significant interaction between gestational age and body weight with prematurity overriding LGA as a risk factor for neonatal morbidity in moderately preterm infants. In study ΙV, we examined the risk of adverse outcome in relation to pre-pregnancy body mass index in a national cohort of 3,457 T1DM pregnancies compared to 764,498 non-diabetic pregnancies. Maternal overweight/obesity increases the risk of adverse outcome in both women with and without T1DM. Within the T1DM cohort, obesity was associated with increased odds of major malformations adjusted OR: 1.77 (1.18-2.65) and preeclampsia adjusted OR: 1.74 (1.35-2.25). T1DM was a significant effect modifier of the association between BMI and major malformations, preeclampsia, LGA and neonatal overweight. Conclusion: In spite of major improvements in the management of type 1 diabetic pregnancies over the years, the present findings clearly demonstrate that T1DM pregnancies still are associated with significantly increased risk of adverse outcomes. An important observation is the rising incidence of LGA infants, which partly can be attributed to a concomitant increase in maternal BMI. This development is worrying as LGA infants face an excess risk of both perinatal and future complications as compared to normal sized infants. The novel and unexpected finding of a gender difference in fetal macrosomia requires further investigations

Efficacy and tolerability of evolocumab vs. ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial

Importance: Muscle-related statin intolerance is reported by 5% to 20% of patients. Objective: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. Design, Setting, and Participants: Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. Interventions: Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). Main Outcome and Measures: Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels. Results: Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, −16.7% (95% CI, −20.5% to −12.9%), absolute change, −31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, −54.5% (95% CI, −57.2% to −51.8%); absolute change, −106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, −16.7% (95% CI, −20.8% to −12.5%); absolute change, −31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, −52.8% (95% CI, −55.8% to −49.8%); absolute change, −102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was −37.8%; absolute difference, −75.8 mg/dL. For week 24, between-group difference in LDL-C was −36.1%; absolute difference, –71.7 mg/dL. Muscle symptoms were reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). Conclusions and Relevance: Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety

Paramedic clinical decision making during high acuity emergency calls: design and methodology of a Delphi study

<p>Abstract</p> <p>Background</p> <p>The scope of practice of paramedics in Canada has steadily evolved to include increasingly complex interventions in the prehospital setting, which likely have repercussions on clinical outcome and patient safety. Clinical decision making has been evaluated in several health professions, but there is a paucity of work in this area on paramedics. This study will utilize the Delphi technique to establish consensus on the most important instances of paramedic clinical decision making during high acuity emergency calls, as they relate to clinical outcome and patient safety.</p> <p>Methods and design</p> <p>Participants in this multi-round survey study will be paramedic leaders and emergency medical services medical directors/physicians from across Canada. In the first round, participants will identify instances of clinical decision making they feel are important for patient outcome and safety. On the second round, the panel will rank each instance of clinical decision making in terms of its importance. On the third and potentially fourth round, participants will have the opportunity to revise the ranking they assigned to each instance of clinical decision making. Consensus will be considered achieved for the most important instances if 80% of the panel ranks it as important or extremely important. The most important instances of clinical decision making will be plotted on a process analysis map.</p> <p>Discussion</p> <p>The process analysis map that results from this Delphi study will enable the gaps in research, knowledge and practice to be identified.</p

Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition diagnosis of malnutrition

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition

Guidance for assessment of the muscle mass phenotypic criterion for the Global Leadership Initiative on Malnutrition (GLIM) diagnosis of malnutrition

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition