Prenatal effects of selective serotonin reuptake inhibitor antidepressants, serotonin transporter promoter genotype (SLC6A4), and maternal mood on child behavior at 3 years of age

To investigate whether prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure affects behavior in 3-year-olds of antenatally anxious or depressed mothers and whether risk was moderated by the serotonin transporter promoter (SLC6A4) genotype.

Genotypic and phenotypic diversity of the noncapsulated Haemophilus influenzae:Adaptation and pathogenesis in the human airways

The human respiratory tract contains a highly adapted microbiota including commensal and opportunistic pathogens. Noncapsulated or nontypable Haemophilus influenzae (NTHi) is a human-restricted member of the normal airway microbiota in healthy carriers and an opportunistic pathogen in immunocompromised individuals. The duality of NTHi as a colonizer and as a symptomatic infectious agent is closely related to its adaptation to the host, which in turn greatly relies on the genetic plasticity of the bacterium and is facilitated by its condition as a natural competent. The variable genotype of NTHi accounts for its heterogeneous gene expression and variable phenotype, leading to differential host-pathogen interplay among isolates. Here we review our current knowledge of NTHi diversity in terms of genotype, gene expression, antigenic variation, and the phenotypes associated with colonization and pathogenesis. The potential benefits of NTHi diversity studies discussed herein include the unraveling of pathogenicity clues, the generation of tools to predict virulence from genomic data, and the exploitation of a unique natural system for the continuous monitoring of long-term bacterial evolution in human airways exposed to noxious agents. Finally, we highlight the challenge of monitoring both the pathogen and the host in longitudinal studies, and of applying comparative genomics to clarify the meaning of the vast NTHi genetic diversity and its translation to virulence phenotypes.

Intrafamilial variation of phenotype in Stargardt macular dystrophy- fundus flavimaculatus

Purpose. To evaluate the intrafamilial phenotypic variation in Stargardt macular dystrophy-Fundus flavimaculatus (SMD-FFM). Methods. Thirty-one siblings from 15 families with SMD-FFM were examined. Age of onset, visual acuity, and clinical features on fundus examination and fundus autofluorescence images, including presence or absence of central and peripheral atrophy and distribution of flecks, were recorded. In addition, electrophysiological studies were undertaken. Results. Large differences between siblings in age of onset (median, 12 years; range, 5-23 years) were observed in six of the 15 families studied, whereas in 9 families differences in age of onset between siblings were small (median, 1 year; range, 0-3 years). Visual acuity varied two or more lines among siblings in nine families. In 10 families (67%) siblings were found to have different clinical appearance on fundus examination and fundus autofluorescence images, whereas in 5 families (33%), affected siblings had similar clinical features. Electrodiagnostic tests were performed on affected members of 12 families and disclosed similar qualitative findings among siblings. In nine families there was loss of central function only; in two, global loss of cone function; and in one, global loss of cone and rod function. Conclusions. In this series, although differences in age of onset, visual acuity, and fundus appearance were observed between siblings, electrophysiological studies demonstrated intrafamilial homogeneity in retinal function. The findings are difficult to reconcile with expression studies showing ABCR transcripts in rod photoreceptors but not in cones.

Quantification of interpoint topographic correlations of threshold values in glaucomatous visual fields

Purpose: The authors sought to quantify neighboring and distant interpoint correlations of threshold values within the visual field in patients with glaucoma. Methods: Visual fields of patients with confirmed or suspected glaucoma were analyzed (n = 255). One eye per patient was included. Patients were examined using the 32 program of the Octopus 1-2-3. Linear regression analysis among each of the locations and the rest of the points of the visual field was performed, and the correlation coefficient was calculated. The degree of correlation was categorized as high (r > 0.66), moderate (0.66 = r > 0.33), or low (r = 0.33). The standard error of threshold estimation was calculated. Results: Most locations of the visual field had high and moderate correlations with neighboring points and with distant locations corresponding to the same nerve fiber bundle. Locations of the visual field had low correlations with those of the opposite hemifield, with the exception of locations temporal to the blind spot. The standard error of threshold estimation increased from 0.6 to 0.9 dB with an r reduction of 0.1. Conclusion: Locations of the visual field have highest interpoint correlation with neighboring points and with distant points in areas corresponding to the distribution of the retinal nerve fiber layer. The quantification of interpoint correlations may be useful in the design and interpretation of visual field tests in patients with glaucoma.

Almost all quantum states have nonclassical correlations

Quantum discord quantifies nonclassical correlations in a quantum system including those not captured by entanglement. Thus, only states with zero discord exhibit strictly classical correlations. We prove that these states are negligible in the whole Hilbert space: typically a state picked out at random has positive discord and, given a state with zero discord, a generic arbitrarily small perturbation drives it to a positive-discord state. These results hold for any Hilbert-space dimension and have direct implications for quantum computation and for the foundations of the theory of open systems. In addition, we provide a simple necessary criterion for zero quantum discord. Finally, we show that, for almost all positive-discord states, an arbitrary Markovian evolution cannot lead to a sudden, permanent vanishing of discord.

Haptoglobin Phenotype, Preeclampsia and Response to Supplementation with Vitamins C and E in Pregnant Women with Type 1 Diabetes.

Objective The phenotype of the antioxidant and pro-angiogenicprotein haptoglobin (Hp) predicts cardiovascular disease risk andtreatment response to antioxidant vitamins in individuals withdiabetes. Our objective was to determine whether Hp phenotypeinfluences pre-eclampsia risk, or the efficacy of vitamins C and Ein preventing pre-eclampsia, in women with type-1 diabetes.
Design This is a secondary analysis of a randomised controlledtrial in which women with diabetes received daily vitamins C andE, or placebo, from 8 to 22 weeks of gestation until delivery.
Setting Twenty-five antenatal metabolic clinics across the UK (innorth-west England, Scotland, and Northern Ireland).
Population Pregnant women with type-1 diabetes.
Methods Hp phenotype was determined in white women whocompleted the study and had plasma samples available (n = 685).
Main outcome measure Pre-eclampsia.
Results Compared with Hp 2-1, Hp 1-1 (OR 0.59, 95% CI 0.30–1.16) and Hp 2-2 (OR 0.93, 95% CI 0.60–1.45) were notassociated with significantly decreased pre-eclampsia risk afteradjusting for treatment group and HbA1c at randomisation. Ourstudy was not powered to detect an interaction between Hpphenotype and treatment response; however, our preliminaryanalysis sugge sts that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype (Hp 1-1, OR 0.77, 95%CI 0.22–2.71; Hp 2-1, OR 0.81, 95% CI 0.46–1.43; Hp 2-2, 0.67,95% CI 0.34–1.33), after adjusting for HbA1c at randomisation.
Conclusions The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes.

Structure-reactivity Correlations in the catalytic coupling of ethyne over novel bimetallic Pd/Sn catalysts

The structure, thermal stability, and catalytic behavior of a novel highly dispersed silica-supported Pd/Sn catalyst prepared by an organometallic route have been examined by X-ray photoelectron, X-ray diffraction, and X-ray absorption, fine structure spectroscopies, the latter two measurements being carried outwith an in situ reaction cell. Additional reactor measurements were performed on a more Sn-rich catalyst and on a pure Pd catalyst. Varying the temperature of reduction induced large variations in catalytic performance toward ethyne-coupling reactions. These changes are understandable in terms of the destruction of SnO2-like structures surrounding the Pd core, yielding a skin of metallic Sn which subsequently undergoes intermixing with Pd. The overall thermal and catalytic behavior of these highly dispersed materials accords well with the analogous single-crystal model system.

Combined genomic and phenotype screening reveals secretory factor SPINK1 as an invasion and survival factor associated with patient prognosis in breast cancer

Secretory factors that drive cancer progression are attractive immunotherapeutic targets. We used a whole-genome data-mining approach on multiple cohorts of breast tumours annotated for clinical outcomes to discover such factors. We identified Serine protease inhibitor Kazal-type 1 (SPINK1) to be associated with poor survival in estrogen receptor-positive (ER+) cases. Immunohistochemistry showed that SPINK1 was absent in normal breast, present in early and advanced tumours, and its expression correlated with poor survival in ER+ tumours. In ER- cases, the prognostic effect did not reach statistical significance. Forced expression and/or exposure to recombinant SPINK1 induced invasiveness without affecting cell proliferation. However, down-regulation of SPINK1 resulted in cell death. Further, SPINK1 overexpressing cells were resistant to drug-induced apoptosis due to reduced caspase-3 levels and high expression of Bcl2 and phospho-Bcl2 proteins. Intriguingly, these anti-apoptotic effects of SPINK1 were abrogated by mutations of its protease inhibition domain. Thus, SPINK1 affects multiple aggressive properties in breast cancer: survival, invasiveness and chemoresistance. Because SPINK1 effects are abrogated by neutralizing antibodies, we suggest that SPINK1 is a viable potential therapeutic target in breast cancer.

Is the number of species on earth increasing or decreasing? Time, chaos and the origin of species

Darwin's On the Origin of Species has led to a theory of evolution with a mass of empirical detail on population genetics below species level, together with heated debate on the details of macroevolutionary patterns above species level. Most of the main principles are clear and generally accepted, notably that life originated once and has evolved over time by descent with modification. Here, I review the fossil and molecular phylogenetic records of the response of life on Earth to Quaternary climatic changes. I suggest that the record can be best understood in terms of the nonlinear dynamics of the relationship between genotype and phenotype, and between climate and environments. 'The origin of species' is essentially unpredictable, but is nevertheless an inevitable consequence of the way that organisms reproduce through time. The process is 'chaotic', but not 'random'. I suggest that biodiversity is best considered as continuously branching systems of lineages, where 'species' are the branch tips. The Earth's biodiversity should thus (1) be in a state of continuous increase and (2) show continuous discrepancies between genetic and morphological data in time and space. © The Palaeontological Association.

Global quantum correlations in finite-size spin chains

We perform an extensive study of the properties of global quantum correlations in finite-size one-dimensional quantum spin models at finite temperature. By adopting a recently proposed measure for global quantum correlations (Rulli and Sarandy 2011 Phys. Rev. A 84 042109), called global discord, we show that critical points can be neatly detected even for many-body systems that are not in their ground state. We consider the transverse Ising model, the cluster-Ising model where three-body couplings compete with an Ising-like interaction, and the nearest-neighbor XX Hamiltonian in transverse magnetic field. These models embody our canonical examples showing the sensitivity of global quantum discord close to criticality. For the Ising model, we find a universal scaling of global discord with the critical exponents pertaining to the Ising universality class.

Glycosylation of low density lipoprotein in patients with type 1 (insulin-dependent) diabetes:correlations with other parameters of glycaemic control

Glycosylation of low density lipoproteins obtained from 16 patients with Type 1 (insulin-dependent) diabetes and from 16 age-, sex-, and race-matched controls, was determined. The diabetic patients were normolipaemic and were in good or fair glycaemic control. Eleven patients performed home blood glucose monitoring. Glycosylation of low density lipoproteins in the diabetic patients was significantly higher (p less than 0.001) than in the control subjects, and was significantly correlated with haemoglobin A1c, (p less than 0.01), glycosylation of plasma proteins, (p less than 0.001), and mean home blood glucose, (p less than 0.01). This study confirms that, in diabetic patients, increased glycosylation of low density lipoprotein occurs to an extent which correlates closely with other commonly used indices of glycaemic control.

Radiation retinopathy--clinical, histopathological, ultrastructural and experimental correlations

Clinical, pathological and experimental studies of radiation retinopathy confirm that the primary vascular event is endothelial cell loss and capillary closure. Pericytes are less susceptible, but typically atrophy as the capillaries become non-functional. The immediate effects of radiation reflect interphase and early mitotic death of injured endothelial cells, whereas later changes may be attributed to delayed mitotic death of compromised endothelial cells as they attempt division in the ordinary course of repair and replacement. Capillary occlusion leads to the formation of dilated capillary collaterals which may remain serviceable and competent for years. Microaneurysms develop in acellular and poorly supported capillaries, predominantly on the arterial side of the circulation and adjacent to regions of poorly perfused retina. Alterations in haemodynamics produce large telangiectatic-like channels which, typically develop a thick collagenous adventitia and may become fenestrated. Limited capillary regeneration occurs, usually evident as recanalisation of arterioles or venules by new capillaries. Vitreo-retinal neovascularisation may occur where retinal ischaemia is widespread. Radiation produces an exaggerated vasculopathy in patients with diabetes mellitus, and five month streptozotocin-induced diabetic rats develop a severe ischaemic retinopathy with vitreoretinal neovascularisation when exposed to 1500 cGy of radiation. Later photocoagulation is useful in containing or reversing microvascular incompetence and vasoproliferation in some patients with advanced radiation retinopathy.

Interaction-induced correlations and non-Markovianity of quantum dynamics

We investigate the conditions under which the trace distance between two different states of a given open system increases in time due to the interaction with an environment, therefore signaling non-Markovianity. We find that the finite-time difference in trace distance is bounded by two sharply defined quantities that are strictly linked to the occurrence of system-environment correlations created throughout their interaction and affecting the subsequent evolution of the system. This allows us to shed light on the origin of non-Markovian behaviors in quantum dynamics. We best illustrate our findings by tackling two physically relevant examples: a non-Markovian dephasing mechanism that has been the focus of a recent experimental endeavor and the open-system dynamics experienced by a spin connected to a finite-size quantum spin chain.