The association of polygenic risk for schizophrenia, bipolar disorder, and depression with neural connectivity in adolescents and young adults: examining developmental and sex differences.

Neurodevelopmental abnormalities in neural connectivity have been long implicated in the etiology of schizophrenia (SCZ); however, it remains unclear whether these neural connectivity patterns are associated with genetic risk for SCZ in unaffected individuals (i.e., an absence of clinical features of SCZ or a family history of SCZ). We examine whether polygenic risk scores (PRS) for SCZ are associated with functional neural connectivity in adolescents and young adults without SCZ, whether this association is moderated by sex and age, and if similar associations are observed for genetically related neuropsychiatric PRS. One-thousand four-hundred twenty-six offspring from 913 families, unaffected with SCZ, were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort (median age at first interview = 15.6 (12-26), 51.6% female, 98.1% European American, 41% with a family history of alcohol dependence). Participants were followed longitudinally with resting-state EEG connectivity (i.e., coherence) assessed every two years. Higher SCZ PRS were associated with elevated theta (3-7 Hz) and alpha (7-12 Hz) EEG coherence. Associations differed by sex and age; the most robust associations were observed between PRS and parietal-occipital, central-parietal, and frontal-parietal alpha coherence among males between ages 15-19 (B: 0.15-0.21, p < 10-4). Significant associations among EEG coherence and Bipolar and Depression PRS were observed, but differed from SCZ PRS in terms of sex, age, and topography. Findings reveal that polygenic risk for SCZ is robustly associated with increased functional neural connectivity among young adults without a SCZ diagnosis. Striking differences were observed between men and women throughout development, mapping onto key periods of risk for the onset of psychotic illness and underlining the critical importance of examining sex differences in associations with neuropsychiatric PRS across development.

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior.

Adult antisocial behavior (AAB) is moderately heritable, relatively common and has adverse consequences for individuals and society. We examined the molecular genetic basis of AAB in 1379 participants from a case-control study in which the cases met criteria for alcohol dependence. We also examined whether genes of interest were expressed in human brain. AAB was measured using a count of the number of Antisocial Personality Disorder criteria endorsed under criterion A from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants were genotyped on the Illumina Human 1M BeadChip. In total, all single-nucleotide polymorphisms (SNPs) accounted for 25% of the variance in AAB, although this estimate was not significant (P=0.09). Enrichment tests indicated that more significantly associated genes were over-represented in seven gene sets, and most were immune related. Our most highly associated SNP (rs4728702, P=5.77 × 10(-7)) was located in the protein-coding adenosine triphosphate-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1). In a gene-based test, ABCB1 was genome-wide significant (q=0.03). Expression analyses indicated that ABCB1 was robustly expressed in the brain. ABCB1 has been implicated in substance use, and in post hoc tests we found that variation in ABCB1 was associated with DSM-IV alcohol and cocaine dependence criterion counts. These results suggest that ABCB1 may confer risk across externalizing behaviors, and are consistent with previous suggestions that immune pathways are associated with externalizing behaviors. The results should be tempered by the fact that we did not replicate the associations for ABCB1 or the gene sets in a less-affected independent sample.

Controlling shot noise in double-barrier magnetic tunnel junctions.

We demonstrate that shot noise in Fe/MgO/Fe/MgO/Fe double-barrier magnetic tunnel junctions is determined by the relative magnetic configuration of the junction and also by the asymmetry of the barriers. The proposed theoretical model, based on sequential tunneling through the system and including spin relaxation, successfully accounts for the experimental observations for bias voltages below 0.5 V, where the influence of quantum well states is negligible. A weak enhancement of conductance and shot noise, observed at some voltages (especially above 0.5 V), indicates the formation of quantum well states in the middle magnetic layer. The observed results open up new perspectives for a reliable magnetic control of the most fundamental noise in spintronic structures.

Interface and temperature dependent magnetic properties in permalloy thin films and tunnel junction structures.

Magnetization dynamics and field dependent magnetization of different devices based on 25-30 nm thick Permalloy (Py) films: such as single Py layers (Py/MgO; Py/CoFeB/Al2O3) and Py inserted as a magnetic layer in magnetic tunnel junctions (Py/CoFe/Al2O3/CoFe; Py/CoFeB/Al2O3/CoFe; Py/MgO/Fe) have been extensively studied within a temperature range between 300 K down to 5 K. The dynamic response was investigated in the linear regime measuring the ferromagnetic resonance response of the Py layers using broadband vector network analyzer technique. Both the static and the dynamic properties suggest the possible presence of a thermally induced spin reorientation transition in the Py interface at temperatures around 60 K in all the samples investigated. It seems, however, that the details of the interface between Py and the hardening ferromagnet/insulator structure, the atomic structure of Py layers (amorphous vs. textured) as well as the presence of dipolar coupling through the insulating barrier in the magnetic tunnel junction structures could strongly influence this low temperature reorientation transition. Our conclusions are indirectly supported by structural characterization of the samples by means of X-Ray diffraction and high resolution transmission electron microscopy techniques. Micromagnetic simulations indicate the possibility of strongly enhanced surface anisotropy in thin Py films over CoFe or CoFeB underlayers. Comparison of the simulations with experimental results also shows that the thermally-induced spin reorientation transition could be influenced by the presence of strong disorder at the surface.

Genome-wide association study of conduct disorder symptomatology.

Conduct disorder (CD) is one of the most prevalent childhood psychiatric conditions, and is associated with a number of serious concomitant and future problems. CD symptomatology is known to have a considerable genetic component, with heritability estimates in the range of 50%. Despite this, there is a relative paucity of studies aimed at identifying genes involved in the susceptibility to CD. In this study, we report results from a genome-wide association study of CD symptoms. CD symptoms were retrospectively reported by a psychiatric interview among a sample of cases and controls, in which cases met the criteria for alcohol dependence. Our primary phenotype was the natural log transformation of the number of CD symptoms that were endorsed, with data available for 3963 individuals who were genotyped on the Illumina Human 1M beadchip array. Secondary analyses are presented for case versus control status, in which caseness was established as endorsing three or more CD symptoms (N = 872 with CD and N = 3091 without CD). We find four markers that meet the criteria for genome-wide significance (P<5 × 10(-8)) with the CD symptom count, two of which are located in the gene C1QTNF7 (C1q and tumor necrosis factor-related protein 7). There were six additional SNPs in the gene that yielded converging evidence of association. These data provide the first evidence of a specific gene that is associated with CD symptomatology. None of the top signals resided in traditional candidate genes, underscoring the importance of a genome-wide approach for identifying novel variants involved in this serious childhood disorder.

Tunneling in double barrier junctions with "hot spots".

We investigate electronic transport in epitaxial Fe(100)/MgO/Fe/MgO/Fe double magnetic tunnel junctions with soft barrier breakdown (hot spots). Specificity of these junctions is continuous middle layer and nitrogen doping of the MgO barriers which provides soft breakdown at biases about 0.5 V. In the junctions with hot spots we observe quasiperiodic changes in the resistance as a function of bias voltage which point out formation of quantum well states in the middle Fe continuous free layer. The room-temperature oscillations have been observed in both parallel and antiparallel magnetic configurations and for both bias polarizations. A simple model of tunneling through hot spots in the double barrier magnetic junction is proposed to qualitatively explain this effect.

[Influence of low doses of ionizing irradiation on parameters of the non-specific immunologically-mediated resistance in persons working in the oil industry].

The authors have determined blood parameters reflected condition of the non-specific immunologically-mediated resistance (NIR) in workers of the oil industry, including persons directly participated in oil wells exploration and exposed for long period of time to low doses of ionizing radiation. The article presents obtained results of the percentage of neutrophils and natural killer cells as well as the level of alpha-interferon in the blood serum. Obtained results demonstrated that parameters of NIR of oil industry workers were not substantively different from analogous parameters of healthy person living in the same region.

[Hemostasis in acute ulcerous bleedings from the stomach and duodenum in experiment].

For the first time in experiment on animals ways of surgical treatment of 'sharp ulcer bleedings' stomach and a duodenal gut with application microporous nikelid-titanic implants are developed, the morphological picture healing processes in ulcer defect with implanted microporous nicelid-titanic plate is studied. Introduction in 'ulcer defect' microporous Ti-Ni implants, the sated 7,5% a solution capropher, provides a stable hemostasis, reduces risk of relapse of bleedings (p < or = 0,05). Possibility of performance of operations by the developed technique is proved at sharp ulcer bleedings of a stomach and a duodenal gut.

Unexpected resonant response in [Fe(001)/Cr(001)]10/MgO(001) multilayers in a magnetic field.

We observed unexpected resonant response in [Fe/Cr]10 multilayers epitaxially grown on MgO(100) substrates which exists only when both ac current and dc magnetic field are simultaneously applied. The magnitude of the resonances is determined by the multilayer magnetization proving their intrinsic character. The reduction of interface epitaxy leads to nonlinear dependence of the magnitude of resonances on the alternating current density. We speculate that the existence of the interface transition zone could facilitate the subatomic vibrations in thin metallic films and multilayers grown on bulk insulating substrates.

[Experimental study of areflux thin-colonic anastomosis formation].

Data experimental a substantiation of a new way of formation are fluxious compression thin-large intestine anastomosis by devices from nicelid titanic alloys are cited. Advantages compression a seam in comparison with manual are shown at studying of mechanical durability, elasticity, biological tightness, a morphological picture of preparations, irrigography. The analysis of postoperative complications is carried out.

Tissue reactions to modern suturing material in colorectal surgery.

Morphological changes in the wall of the large intestine were studied after its manual suturing by a double-row interrupted suture with modern suture threads. Light and scanning electron microscopy showed "fuse properties" and "sawing effect" of polyfilament twisted threads (e.g. vicryl). Monofilament threads were free from these drawbacks and therefore were preferable. Metal elastic threads on the basis of titanium-nickelide alloys caused no inflammatory changes in tissues.

Shot noise in magnetic tunnel junctions: evidence for sequential tunneling.

We report the experimental observation of sub-Poissonian shot noise in single magnetic tunnel junctions, indicating the importance of tunneling via impurity levels inside the tunnel barrier. For junctions with weak zero-bias anomaly in conductance, the Fano factor (normalized shot noise) depends on the magnetic configuration being enhanced for antiparallel alignment of the ferromagnetic electrodes. We propose a model of sequential tunneling through nonmagnetic and paramagnetic impurity levels inside the tunnel barrier to qualitatively explain the observations.

[Method of forming of compressive terminal colon anastomosis].

The method of creation of compressive terminal colon anastomosis with implants of TN-10 titanium nikelid was developed. Experimental studies carried out on 60 mongrel dogs demonstrated higher physical strength and biological containment of these anastomoses compared with manual and mechanical ones. Regeneration completed earlier after surgery and was accompanied by less inflammation. Clinical study was carried out in 54 patients. There were no lethal outcomes, insufficiency of anastomosis was seen in 1 (1.9%) case.

[Vagotomy in the treatment of bleeding reflux-esophagitis and gastroduodenal bleedings]. / Vagotomiia v lechenii krovotochashchego refliuks-ézofagita i gastroduodenal'nykh krovotechenii

Fifteen-year experience in the treatment of 588 patients with esophageal and gastroduodenal bleedings is analyzed. Surgery was performed in 286 patients, 302 patients were treated conservatively including 71 patients who underwent endoscopic procedures. Principles of differentiated treatment policy are developed. Selective proximal vagotomy in combination with fundoplication (if indicated, with surgeries draining the stomach) is surgery of choice in bleeding reflux-esophagitis and gastroduodenal ulcerous bleedings. These methods eliminate pathogenetic factors of bleeding gastro-esophageal reflux, lower acidity of gastric juice.

Near-field short range correlation in optical waves transmitted through random media.

Two-dimensional near-field images of light transmitted through a disordered dielectric structure have been measured for two probe wavelengths. From these data, the 2D spatial dependence of the intensity correlation function, C(deltaR-->), has been extracted. We observe that the spatial dependence of C is dominated by a rapidly varying feature determined by the wavelength of the probe light and the average refractive index of the material, as expected by theory. Finally, we deduce the absolute value of the effective refractive index by fitting the theoretical spatial dependence of C to our experimental results.

Near-field measurement of short-range correlation in optical waves transmitted through random media.

Two-dimensional near-field images of speckle patterns formed by optical waves transmitted through a disordered porous silica glass sample are measured. The corresponding 2D intensity correlation function, C, is extracted. The subwavelength spatial resolution of near-field microscopy allows us to resolve in the spatial distribution of C the expected subwavelength oscillations and to follow their dependence on the excitation wavelength. Finally, we deduce the effective refractive index of the material by fitting the theoretical spatial dependence of C to our experimental results.

Low frequency magnetic response in antiferromagnetically coupled Fe/Cr multilayers.

The magnetic field and temperature dependence of the low frequency magnetic response of antiferromagnetically coupled Fe/Cr(100) multilayers has been studied between +/-500 Oe, from 2 to 300 K. At T = 2 K the losses exhibit an unusually strong frequency dependence which can be described within a single relaxation time scheme. This relaxation time proves to be strongly field dependent. These phenomena are specific for epitaxial multilayers with large magnetoresistance. The behavior of the relaxation time at low temperatures might be related to some quantum tunneling processes.

[Efficacy of quadropril (spirapril) vs capropril in treatment of essential hypertension]. / Effektivnost' kvadroprila (spiraprila) i kaptoprila pri éssentsial'noi gipertonii (gipertonicheskoi bolezni).

AIM: To compare the efficacy of monotherapy with quadropril (spirapril) vs captopril in essential hypertension. MATERIAL AND METHODS: 20 female patients aged 55 +/- 2 years with moderate hypertension (WHO classification) were included in the study. 16 patients had congestive heart failure stage II NYHA and 4 patients stage III NYHA. ECG and echocardiography were performed in all the patients. Two patient groups of 10 patients were treated for 6 weeks. Group 1 received 6 mg quadropril once daily. Group 2 received 25 mg captopril 3 times daily. The therapy was considered to be efficient if diastolic pressure (BP) was reduced to 90 +/- 5 mm Hg and systolic BP to 140 +/- 10 mm Hg from baseline values in the range of 210/120-170/100 mm Hg. RESULTS: The hypotensive effect of quadropril resulted in stabilisation of BP during the second week of therapy. A significant BP decrease was achieved at the end of 6 week therapy. Systolic BP fell from 178.8 +/- 3.2 to 145 +/- 5.6 mm Hd and diastolic BP from 109.7 +/- 1.2 to 92.4 +/- 1.7 mm Hg. Central and cardiac hemodynamic parameters improved. In one patient the condition improved from CHF stage III to stage II NYHA. No adverse effects were observed. A hypotensive effect of captopril reduced significantly systolic blood pressure from 182.1 +/- 2.7 to 150 +/- 4.6 mm Hg and diastolic BP from 110.4 +/- 1.1 to 100.1 +/- 1.9 mm Hg. Two patients developed adverse effects: cough and chest dyscomfort. CONCLUSION: Quadropril monotherapy showed to be more effective in diastolic BP decrease compared with captopril monotherapy and had advantages in one daily dose regimen, absence of the first dose effect and side effects.