Strategies for Cross-Examining Expert Witnesses: Social Scientists' Encounter with Attorneys in the School Desegregation Cases

http://deepblue.lib.umich.edu/bitstream/2027.42/51078/1/310.pd

Prevalence of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review of the literature

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Understanding of PAH prevalence remains limited, but PAH has been reported as a frequent complication in connective tissue diseases. This study estimated prevalence of PAH in patients with connective tissue diseases and prevalence of idiopathic PAH using a systematic review of the literature. We searched PubMed through May 19, 2012 for all studies on prevalence of PAH in patients with connective tissue diseases or prevalence of idiopathic PAH. To be included, studies had to be in English, have humans as subjects, and determine prevalence within a time interval of up to 2 years. Studies only investigating pediatric patients were excluded. Pooled prevalence estimates were calculated. Twenty studies were identified in the review. Seventeen of the 20 studies reported prevalence of PAH in connective tissue diseases and three reported prevalence of idiopathic PAH. The pooled prevalence estimate of idiopathic PAH was 12 cases per million population (95 % CI 5 cases per million to 22 cases per million) with estimates ranging from 5.9 cases per million population to 25 cases per million population. The pooled prevalence estimate of PAH in patients with connective tissue diseases was 13 % (95 % CI, 9.18 % to 18.16 %) with reported estimates ranging from 2.8 % to 32 %. Prevalence of PAH in patients with connective tissue diseases was substantially higher than that of idiopathic PAH based on pooled prevalence estimates. Comparisons of PAH prevalence in persons with connective tissue disease and idiopathic PAH using a large observational study would be helpful in better assessing relative prevalence

A Complicated Course of Brain Tumor Resection in a Patient with a Left Ventricular Assist Device

Left ventricular assist devices (LVAD) are mechanical pumps that have become a standard treatment for end-stage heart failure. As patients with LVAD are living longer, the number of noncardiac surgeries performed in these patients is rising. However, these patients present a unique set of risk factors, some of which include acquired coagulopathies, anticoagulation status, and hemodynamic instability. Thus, performing noncardiac surgeries in patients with an LVAD requires a precise and complex surgical strategy with optimal communication among the surgical team. Therefore, knowledge of best perioperative approaches for patients with LVAD is urgently needed. Here, we present a detailed perioperative surgical approach in the case of a brain tumor resection for a 62-year-old patient with an LVAD whose course was complicated with a brain hematoma. Critical details include key aspects of monitoring patient hemodynamic stability and handling of anesthesia, patient positioning, and antiplatelet and anticoagulation drug therapy. This case highlights the importance for anesthesiologists to be well informed about perioperative LVAD management, as well as common complications that they may encounter

Clonal and microclonal mutational heterogeneity in high hyperdiploid acute lymphoblastic leukemia.

High hyperdiploidy (HD), the most common cytogenetic subtype of B-cell acute lymphoblastic leukemia (B-ALL), is largely curable but significant treatment-related morbidity warrants investigating the biology and identifying novel drug targets. Targeted deep-sequencing of 538 cancer-relevant genes was performed in 57 HD-ALL patients lacking overt KRAS and NRAS hotspot mutations and lacking common B-ALL deletions to enrich for discovery of novel driver genes. One-third of patients harbored damaging mutations in epigenetic regulatory genes, including the putative novel driver DOT1L (n=4). Receptor tyrosine kinase (RTK)/Ras/MAPK signaling pathway mutations were found in two-thirds of patients, including novel mutations in ROS1, which mediates phosphorylation of the PTPN11-encoded protein SHP2. Mutations in FLT3 significantly co-occurred with DOT1L (p=0.04), suggesting functional cooperation in leukemogenesis. We detected an extraordinary level of tumor heterogeneity, with microclonal (mutant allele fraction <0.10) KRAS, NRAS, FLT3, and/or PTPN11 hotspot mutations evident in 31/57 (54.4%) patients. Multiple KRAS and NRAS codon 12 and 13 microclonal mutations significantly co-occurred within tumor samples (p=4.8x10-4), suggesting ongoing formation of and selection for Ras-activating mutations. Future work is required to investigate whether tumor microheterogeneity impacts clinical outcome and to elucidate the functional consequences of epigenetic dysregulation in HD-ALL, potentially leading to novel therapeutic approaches

The female protective effect in autism spectrum disorder is not mediated by a single genetic locus

Background: A 4:1 male to female sex bias has consistently been observed in autism spectrum disorder (ASD). Epidemiological and genetic studies suggest a female protective effect (FPE) may account for part of this bias; however, the mechanism of such protection is unknown. Quantitative assessment of ASD symptoms using the Social Responsiveness Scale (SRS) shows a bimodal distribution unique to females in multiplex families. This leads to the hypothesis that a single, common genetic locus on chromosome X might mediate the FPE and produce the ASD sex bias. Such a locus would represent a major therapeutic target and is likely to have been missed by conventional genome-wide association study (GWAS) analysis. Methods: To explore this possibility, we performed an association study in affected versus unaffected females, considering three tiers of single nucleotide polymorphisms (SNPs) as follows: 1) regions of chromosome X that escape X-inactivation, 2) all of chromosome X, and 3) genome-wide. Results: No evidence of a SNP meeting the criteria for a single FPE locus was observed, despite the analysis being well powered to detect this effect. Conclusions: The results do not support the hypothesis that the FPE is mediated by a single genetic locus; however, this does not exclude the possibility of multiple genetic loci playing a role in the FPE.Intellectual and Developmental Disabilities Research Center at Washington University (NIH/NICHD) [P30 HD062171]; Simons Foundation (SFARI) [307705]; Canadian Institutes of Health Research; [R01 HD042541]SCI(E)[email protected]; [email protected]

STIS ultraviolet/optical spectroscopy of `warm' ultraluminous infrared galaxies

(Abridged) We present high spatial resolution ultraviolet and optical spectroscopy, obtained using the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope, of nuclear structures within four `warm' Ultraluminous Infrared Galaxies (ULIRGs). We find an AGN in at least three, and probably all four of our sample, hosted in a compact, optically luminous `knot'. In three cases these knots were previously identified as a putative AGN nucleus from multiband optical imaging. Three of the sample also harbor a starburst in one or more knots, suggesting that the optically luminous knots seen in local ULIRGs are the most likely sites of the dust-shrouded starburst and AGN activity that power the infrared emission. The four AGN have a diverse range of properties; two are classical narrow line AGN, one shows both broad and narrow lines and evidence for lines of sight from the narrow through to the broad line regions, and one is plausibly a FeLoBAL AGN. The probable presence in one object of an FeLoBAL AGN, which are extremely rare in the QSO population, supports the idea that LoBAL AGN may be youthful systems shrouded in gas and dust rather than AGN viewed along a certain line of sight. The three starbursts for which detailed constraints are possible show a smaller range in properties; all three bursts are young with two having ages of ~4Myr and the third having an age of 20Myr, suggesting that ULIRGs undergo several bursts of star formation during their lifetimes. None of the starbursts show evidence for Initial Mass Function slopes steeper than about 3.3. The metallicities of the knots for which metallicities can be derived are all at least 1.5 times the Solar value. The properties of one further starburst knot are consistent with it being the forming core of an elliptical galaxy.Comment: ApJ, accepte

Electrophysiological effects of 5-hydroxytryptamine on isolated human atrial myocytes, and the influence of chronic beta-adrenoceptor blockade

<b>1.</b> 5-Hydroxytryptamine (5-HT) has been postulated to play a proarrhythmic role in the human atria via stimulation of 5-HT<sub>4</sub> receptors. <b>2.</b> The aims of this study were to examine the effects of 5-HT on the L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>) action potential duration (APD), the effective refractory period (ERP) and arrhythmic activity in human atrial cells, and to assess the effects of prior treatment with β-adrenoceptor antagonists. <b>3.</b> Isolated myocytes, from the right atrial appendage of 27 consenting patients undergoing cardiac surgery who were in sinus rhythm, were studied using the whole-cell perforated patch-clamp technique at 37ºC. <b>4.</b> 5-HT (1 n-10 μM) caused a concentration-dependent increase in <i>I</i><sub>CaL</sub>, which was potentiated in cells from β-blocked (maximum response to 5-HT, E<sub>max</sub>=299±12% increase above control) compared to non-β-blocked patients (E<sub>max</sub>=220±6%, P<0.05), but with no change in either the potency (log EC<sub>50</sub>: -7.09±0.07 vs -7.26±0.06) or Hill coefficient (<i>n</i><sub>H</sub>: 1.5±0.6 vs 1.5±0.3) of the 5-HT concentration-response curve. <b>5.</b> 5-HT (10 μM) produced a greater increase in the APD at 50% repolarisation (APD50) in cells from β-blocked patients (of 37±10 ms, i.e. 589±197%) vs non-β-blocked patients (of 10±4 ms, i.e. 157±54%; P<0.05). Both the APD<sub>90</sub> and the ERP were unaffected by 5-HT. <b>6.</b> Arrhythmic activity was observed in response to 5-HT in five of 17 cells (29%) studied from β-blocked, compared to zero of 16 cells from the non-β-blocked patients (P<0.05). <b>7.</b> In summary, the 5-HT-induced increase in calcium current was associated with a prolonged early plateau phase of repolarisation, but not late repolarisation or refractoriness, and the enhancement of these effects by chronic β-adrenoceptor blockade was associated with arrhythmic potential

Topological Phases near a Triple Degeneracy

We study the pattern of three state topological phases that appear in systems with real Hamiltonians and wave functions. We give a simple geometric construction for representing these phases. We then apply our results to understand previous work on three state phases. We point out that the ``mirror symmetry'' of wave functions noticed in microwave experiments can be simply understood in our framework.Comment: 4 pages, 1 figure, to appear in Phys. Rev. Let