Mortality of Patients with Hematological Malignancy after Admission to the Intensive Care Unit

Background: The admission of patients with malignancies to an intensive care unit (ICU) still remains a matter of substantial controversy. The identification of factors that potentially influence the patient outcome can help ICU professionals make appropriate decisions. Patients and Methods: 90 adult patients with hematological malignancy (leukemia 47.8%, high-grade lymphoma 50%) admitted to the ICU were analyzed retrospectively in this single-center study considering numerous variables with regard to their influence on ICU and day-100 mortality. Results: The median simplified acute physiology score (SAPS) II at ICU admission was 55 (ICU survivors 47 vs. 60.5 for non-survivors). The overall ICU mortality rate was 45.6%. With multivariate regression analysis, patients admitted with sepsis and acute respiratory failure had a significantly increased ICU mortality (sepsis odds ratio (OR) 9.12, 95% confidence interval (CI) 1.1-99.7, p = 0.04; respiratory failure OR 13.72, 95% CI 1.39-136.15, p = 0.025). Additional factors associated with an increased mortality were: high doses of catecholamines (ICU: OR 7.37, p = 0.005; day 100: hazard ratio (HR) 2.96, p < 0.0001), renal replacement therapy (day 100: HR 1.93, p = 0.026), and high SAPS II (ICU: HR 1.05, p = 0.038; day 100: HR 1.2, p = 0.027). Conclusion: The decision for or against ICU admission of patients with hematological diseases should become increasingly independent of the underlying malignant disease

Ready or not? Expectations of faculty and medical students for clinical skills preparation for clerkships

Background: Preclerkship clinical-skills training has received increasing attention as a foundational preparation for clerkships. Expectations among medical students and faculty regarding the clinical skills and level of skill mastery needed for starting clerkships are unknown. Medical students, faculty teaching in the preclinical setting, and clinical clerkship faculty may have differing expectations of students entering clerkships. If students&#x0027; expectations differ from faculty expectations, students may experience anxiety. Alternately, congruent expectations among students and faculty may facilitate integrated and seamless student transitions to clerkships. Aims: To assess the congruence of expectations among preclerkship faculty, clerkship faculty, and medical students for the clinical skills and appropriate level of clinical-skills preparation needed to begin clerkships. Methods: Investigators surveyed preclinical faculty, clerkship faculty, and medical students early in their basic clerkships at a North American medical school that focuses on preclerkship clinical-skills development. Survey questions assessed expectations for the appropriate level of preparation in basic and advanced clinical skills for students entering clerkships. Results: Preclinical faculty and students had higher expectations than clerkship faculty for degree of preparation in most basic skills. Students had higher expectations than both faculty groups for advanced skills preparation. Conclusions: Preclinical faculty, clerkship faculty, and medical students appear to have different expectations of clinical-skills training needed for clerkships. As American medical schools increasingly introduce clinical-skills training prior to clerkships, more attention to alignment, communication, and integration between preclinical and clerkship faculty will be important to establish common curricular agendas and increase integration of student learning. Clarification of skills expectations may also alleviate student anxiety about clerkships and enhance their learning

The development and application of a new tool to assess the adequacy of the content and timing of antenatal care

Abstract Background: Current measures of antenatal care use are limited to initiation of care and number of visits. This study aimed to describe the development and application of a tool to assess the adequacy of the content and timing of antenatal care. Methods: The Content and Timing of care in Pregnancy (CTP) tool was developed based on clinical relevance for ongoing antenatal care and recommendations in national and international guidelines. The tool reflects minimal care recommended in every pregnancy, regardless of parity or risk status. CTP measures timing of initiation of care, content of care (number of blood pressure readings, blood tests and ultrasound scans) and whether the interventions were received at an appropriate time. Antenatal care trajectories for 333 pregnant women were then described using a standard tool (the APNCU index), that measures the quantity of care only, and the new CTP tool. Both tools categorise care into 4 categories, from ‘Inadequate’ (both tools) to ‘Adequate plus’ (APNCU) or ‘Appropriate’ (CTP). Participants recorded the timing and content of their antenatal care prospectively using diaries. Analysis included an examination of similarities and differences in categorisation of care episodes between the tools. Results: According to the CTP tool, the care trajectory of 10,2% of the women was classified as inadequate, 8,4% as intermediate, 36% as sufficient and 45,3% as appropriate. The assessment of quality of care differed significantly between the two tools. Seventeen care trajectories classified as ‘Adequate’ or ‘Adequate plus’ by the APNCU were deemed ‘Inadequate’ by the CTP. This suggests that, despite a high number of visits, these women did not receive the minimal recommended content and timing of care. Conclusions: The CTP tool provides a more detailed assessment of the adequacy of antenatal care than the current standard index. However, guidelines for the content of antenatal care vary, and the tool does not at the moment grade over-use of interventions as ‘Inappropriate’. Further work needs to be done to refine the content items prior to larger scale testing of the impact of the new measure

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

The quasar feedback survey: discovering hidden Radio-AGN and their connection to the host galaxy ionized gas

We present the first results from the Quasar Feedback Survey, a sample of 42 z 1042.1 ergs s−1) with moderate radio luminosities (i.e. L1.4GHz > 1023.4 W Hz−1; median L1.4GHz = 5.9 × 1023 W Hz−1). Using high spatial resolution (∼0.3–1 arcsec), 1.5–6 GHz radio images from the Very Large Array, we find that 67 per cent of the sample have spatially extended radio features on ∼1–60 kpc scales. The radio sizes and morphologies suggest that these may be lower radio luminosity versions of compact, radio-loud AGNs. By combining the radio-to-infrared excess parameter, spectral index, radio morphology, and brightness temperature, we find radio emission in at least 57 per cent of the sample that is associated with AGN-related processes (e.g. jets, quasar-driven winds, or coronal emission). This is despite only 9.5–21 per cent being classified as radio-loud using traditional criteria. The origin of the radio emission in the remainder of the sample is unclear. We find that both the established anticorrelation between radio size and the width of the [O III] line, and the known trend for the most [O III] luminous AGNs to be associated with spatially extended radio emission, also hold for our sample of moderate radio luminosity quasars. These observations add to the growing evidence of a connection between the radio emission and ionized gas in quasar host galaxies. This work lays the foundation for deeper investigations into the drivers and impact of feedback in this unique sample

Strings on Bubbling Geometries

We study gauge theory operators which take the form of a product of a trace with a Schur polynomial, and their string theory duals. These states represent strings excited on bubbling AdS geometries which are dual to the Schur polynomials. These geometries generically take the form of multiple annuli in the phase space plane. We study the coherent state wavefunction of the lattice, which labels the trace part of the operator, for a general Young tableau and their dual description on the droplet plane with a general concentric ring pattern. In addition we identify a density matrix over the coherent states on all the geometries within a fixed constraint. This density matrix may be used to calculate the entropy of a given ensemble of operators. We finally recover the BMN string spectrum along the geodesic near any circle from the ansatz of the coherent state wavefunction.Comment: 41 pages, 12 figures, published version in JHE

Aerobic capacity, activity levels and daily energy expenditure in male and female adolescents of the kenyan nandi sub-group

The relative importance of genetic and socio-cultural influences contributing to the success of east Africans in endurance athletics remains unknown in part because the pre-training phenotype of this population remains incompletely assessed. Here cardiopulmonary fitness, physical activity levels, distance travelled to school and daily energy expenditure in 15 habitually active male (13.9±1.6 years) and 15 habitually active female (13.9±1.2) adolescents from a rural Nandi primary school are assessed. Aerobic capacity ([Formula: see text]) was evaluated during two maximal discontinuous incremental exercise tests; physical activity using accelerometry combined with a global positioning system; and energy expenditure using the doubly labelled water method. The [Formula: see text] of the male and female adolescents were 73.9±5.7 ml(.) kg(-1.) min(-1) and 61.5±6.3 ml(.) kg(-1.) min(-1), respectively. Total time spent in sedentary, light, moderate and vigorous physical activities per day was 406±63 min (50% of total monitored time), 244±56 min (30%), 75±18 min (9%) and 82±30 min (10%). Average total daily distance travelled to and from school was 7.5±3.0 km (0.8-13.4 km). Mean daily energy expenditure, activity-induced energy expenditure and physical activity level was 12.2±3.4 MJ(.) day(-1), 5.4±3.0 MJ(.) day(-1) and 2.2±0.6. 70.6% of the variation in [Formula: see text] was explained by sex (partial R(2) = 54.7%) and body mass index (partial R(2) = 15.9%). Energy expenditure and physical activity variables did not predict variation in [Formula: see text] once sex had been accounted for. The highly active and energy-demanding lifestyle of rural Kenyan adolescents may account for their exceptional aerobic fitness and collectively prime them for later training and athletic success

Isolated Hypoxic Hepatic Perfusion with Retrograde Outflow in Patients with Irresectable Liver Metastases; A New Simplified Technique in Isolated Hepatic Perfusion

Background: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic h

The influence of speed and size on avian terrestrial locomotor biomechanics: predicting locomotion in extinct theropod dinosaurs

How extinct, non-avian theropod dinosaurs moved is a subject of considerable interest and controversy. A better understanding of non-avian theropod locomotion can be achieved by better understanding terrestrial locomotor biomechanics in their modern descendants, birds. Despite much research on the subject, avian terrestrial locomotion remains little explored in regards to how kinematic and kinetic factors vary together with speed and body size. Here, terrestrial locomotion was investigated in twelve species of ground-dwelling bird, spanning a 1,780-fold range in body mass, across almost their entire speed range. Particular attention was devoted to the ground reaction force (GRF), the force that the feet exert upon the ground. Comparable data for the only other extant obligate, striding biped, humans, were also collected and studied. In birds, all kinematic and kinetic parameters examined changed continuously with increasing speed, while in humans all but one of those same parameters changed abruptly at the walk-run transition. This result supports previous studies that show birds to have a highly continuous locomotor repertoire compared to humans, where discrete ‘walking’ and ‘running’ gaits are not easily distinguished based on kinematic patterns alone. The influences of speed and body size on kinematic and kinetic factors in birds are developed into a set of predictive relationships that may be applied to extinct, non-avian theropods. The resulting predictive model is able to explain 79–93% of the observed variation in kinematics and 69–83% of the observed variation in GRFs, and also performs well in extrapolation tests. However, this study also found that the location of the whole-body centre of mass may exert an important influence on the nature of the GRF, and hence some caution is warranted, in lieu of further investigation