Specific heat and non-linear susceptibility in spin glasses with random fields

We study magnetic properties of spin glass SG systems under a random field (RF), beased on the suggestion that RFs can be induced by a weak transverse field in the compound LiHo$_x$Y$_{1-x}$F$_4$. We consider a cluster spin model that allows long-range disordered interactions among clusters and short-range interactions inside the clusters, besides a local RF for each spin following a Gaussian distribution with standard deviation $\Delta$. We adopt the one-step replica symmetry breaking (RSB) approach to get an exactly solvable single-cluster problem. We discuss the behavior of order parameters, specific heat $C_{m}$, nonlinear susceptibility $\chi_3$ and phase diagrams for different disorder configurations. In the absence of RF, the $\chi_3$ exhibits a divergence at $T_f$, while the $C_{m}$ shows a broad maximum at a temperature $T^{**}$ around 30$\%$ above $T_f$, as expected for conventional SG systems. The presence of RF changes this scenario. The $C_{m}$ still shows the maximum at $T^{**}$ that is weakly dependent on $\Delta$. However, the $T_f$ is displaced to lower temperatures, enhancing considerable the ration $T^{**}/T_f$. Furthermore, the divergence in $\chi_3$ is replaced by a rounded maximum at a temperature $T^{*}$, which becomes increasingly higher than $T_f$ as $\Delta$ enhances. As a consequence, the paramagnetic phase is unfolded in three regions: (i) a conventional paramagnetism ($T>T^{**}$; (ii) a region with formation of short-range order with frozen spins ($T^{*}<T<T^{**}$); (iii) a region with slow growth of free-energy barriers slowing down the spin dynamics before the SG transition ($T_f<T<T^{*}$) suggesting an intermediate Griffiths phase before the SG state. Our results reproduce qualitatively some findings of LiHo$_x$Y$_{1-x}$F$_4$ as the rounded maximum of $\chi_3$ behavior triggered by RF.Comment: 9 pages, 6 figure

Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

Extracorporeal CO2 Removal: The Minimally Invasive Approach, Theory, and Practice

Objectives: Minimally invasive extracorporeal CO2 removal is an accepted supportive treatment in chronic obstructive pulmonary disease patients. Conversely, the potential of such technique in treating acute respiratory distress syndrome patients remains to be investigated. The aim of this study was: 1) to quantify membrane lung CO2 removal (Vco2ML) under different conditions and 2) to quantify the natural lung CO2 removal (Vco2NL) and to what extent mechanical ventilation can be reduced while maintaining total expired CO2 (Vco2tot = Vco2ML + Vco2NL) and arterial Pco2 constant. Design: Experimental animal study. Setting: Department of Experimental Animal Medicine, University of G\uf6ttingen, Germany. Subjects: Eight healthy pigs (57.7 \ub1 5 kg). Interventions: The animals were sedated, ventilated, and connected to the artificial lung system (surface 1.8 m2, polymethylpentene membrane, filling volume 125 mL) through a 13F catheter. Vco2ML was measured under different combinations of inflow Pco2 (38.9 \ub1 3.3, 65 \ub1 5.7, and 89.9 \ub1 12.9 mm Hg), extracorporeal blood flow (100, 200, 300, and 400 mL/min), and gas flow (4, 6, and 12 L/min). At each setting, we measured Vco2ML, Vco2NL, lung mechanics, and blood gases. Measurements and Main Results: Vco2ML increased linearly with extracorporeal blood flow and inflow Pco2 but was not affected by gas flow. The outflow Pco2 was similar regardless of inflow Pco2 and extracorporeal blood flow, suggesting that Vco2ML was maximally exploited in each experimental condition. Mechanical ventilation could be reduced by up to 80-90% while maintaining a constant Paco2. Conclusions: Minimally invasive extracorporeal CO2 removal removes a relevant amount of CO2 thus allowing mechanical ventilation to be significantly reduced depending on extracorporeal blood flow and inflow Pco2. Extracorporeal CO2 removal may provide the physiologic prerequisites for controlling ventilator-induced lung injury

Association of MSX1 and TGFB3 with nonsyndromic clefting in humans.

Nonsyndromic cleft lip with or without cleft palate (CL/P) and nonsyndromic cleft palate only (CPO) are common congenital anomalies with significant medical, psychological, social, and economic ramifications. Both CL/P and CPO are examples of complex genetic traits. There exists sufficient evidence to hypothesize that disease loci for CL/P and CPO can be identified by a candidate-gene linkage-disequilibrium (LD) strategy. Candidate genes for clefting, including TGFA, BCL3, DLX2, MSX1, and TGFB3, were screened for LD with either CL/P or CPO in a predominantly Caucasian population, with both case-control- and nuclear-family-based approaches. Previously reported LD for TGFA with both CL/P and CPO could not be confirmed, except in CL/P patients with a positive family history. Also, in contrast to previous studies, no LD was found between BCL3 and either CL/P or CPO. Significant LD was found between CL/P and both MSX1 and TGFB3 and between CPO and MSX1, suggesting that these genes are involved in the pathogenesis of clefting. In addition, a mutation search in the genes DLX2, MSX1, and TGFB3 was performed in 69 CPO patients and in a subset of the CL/P patients. No common mutations were found in the coding regions of these genes; however, several rare variants of MSX1 and TGFB3 were found that may alter the latters' normal function. These results form the basis for future research, including (a) mutation searches in the MSX1 and TGFB3 genes in Caucasian CL/P patients and (b) extension of the search for MSX1 mutations in CPO patients to the noncoding regions

Positive end-expiratory pressure and mechanical power

Editor's Perspective What We Already Know about This Topic Positive end-expiratory pressure protects against ventilation-induced lung injury by improving homogeneity of ventilation, but positive end-expiratory pressure contributes to the mechanical power required to ventilate the lung What This Article Tells Us That Is New This in vivo study (36 pigs mechanically ventilated in the prone position) suggests that low levels of positive end-expiratory pressure reduce injury associated with atelectasis, and above a threshold level of power, positive end-expiratory pressure causes lung injury and adverse hemodynamics Background: Positive end-expiratory pressure is usually considered protective against ventilation-induced lung injury by reducing atelectrauma and improving lung homogeneity. However, positive end-expiratory pressure, together with tidal volume, gas flow, and respiratory rate, contributes to the mechanical power required to ventilate the lung. This study aimed at investigating the effects of increasing mechanical power by selectively modifying its positive end-expiratory pressure component. Methods: Thirty-six healthy piglets (23.3 \ub1 2.3 kg) were ventilated prone for 50 h at 30 breaths/min and with a tidal volume equal to functional residual capacity. Positive end-expiratory pressure levels (0, 4, 7, 11, 14, and 18 cm H2O) were applied to six groups of six animals. Respiratory, gas exchange, and hemodynamic variables were recorded every 6 h. Lung weight and wet-to-dry ratio were measured, and histologic samples were collected. Results: Lung mechanical power was similar at 0 (8.8 \ub1 3.8 J/min), 4 (8.9 \ub1 4.4 J/min), and 7 (9.6 \ub1 4.3 J/min) cm H2O positive end-expiratory pressure, and it linearly increased thereafter from 15.5 \ub1 3.6 J/min (positive end-expiratory pressure, 11 cm H2O) to 18.7 \ub1 6 J/min (positive end-expiratory pressure, 14 cm H2O) and 22 \ub1 6.1 J/min (positive end-expiratory pressure, 18 cm H2O). Lung elastances, vascular congestion, atelectasis, inflammation, and septal rupture decreased from zero end-expiratory pressure to 4 to 7 cm H2O (P &lt; 0.0001) and increased progressively at higher positive end-expiratory pressure. At these higher positive end-expiratory pressure levels, striking hemodynamic impairment and death manifested (mortality 0% at positive end-expiratory pressure 0 to 11 cm H2O, 33% at 14 cm H2O, and 50% at 18 cm H2O positive end-expiratory pressure). From zero end-expiratory pressure to 18 cm H2O, mean pulmonary arterial pressure (from 19.7 \ub1 5.3 to 32.2 \ub1 9.2 mmHg), fluid administration (from 537 \ub1 403 to 2043 \ub1 930 ml), and noradrenaline infusion (0.04 \ub1 0.09 to 0.34 \ub1 0.31 \u3bcg \ub7 kg-1 \ub7 min-1) progressively increased (P &lt; 0.0001). Lung weight and lung wet-to-dry ratios were not significantly different across the groups. The lung mechanical power level that best discriminated between more versus less severe damage was 13 \ub1 1 J/min. Conclusions: Less than 7 cm H2O positive end-expiratory pressure reduced atelectrauma encountered at zero end-expiratory pressure. Above a defined power threshold, sustained positive end-expiratory pressure contributed to potentially lethal lung damage and hemodynamic impairment