Interleukin 3 and schizophrenia:the impact of sex and family history

Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.

First steps: study protocol for a randomized controlled trial of the effectiveness of the Group Family Nurse Partnership (gFNP) program compared to routine care in improving outcomes for high-risk mothers and their children and preventing abuse

Background: Evidence from the USA suggests that the home-based Family Nurse Partnership program (FNP), extending from early pregnancy until infants are 24 months, can reduce the risk of child abuse and neglect throughout childhood. FNP is now widely available in the UK. A new variant, Group Family Nurse Partnership (gFNP) offers similar content but in a group context and for a shorter time, until infants are 12 months old. Each group comprises 8 to 12 women with similar expected delivery dates and their partners. Its implementation has been established but there is no evidence of its effectiveness.

Methods/Design: The study comprises a multi-site randomized controlled trial designed to identify the benefits of gFNP compared to standard care. Participants (not eligible for FNP) must be either aged <20 years at their last menstrual period (LMP) with one or more previous live births, or aged 20 to 24 at LMP with low educational qualifications and no previous live births. 'Low educational qualifications' is defined as not having both Maths and English Language GCSE at grade C or higher or, if they have both, no more than four in total at grade C or higher. Exclusions are: under 20 years and previously received home-based FNP and, in either age group, severe psychotic mental illness or not able to communicate in English. Consenting women are randomly allocated (minimized by site and maternal age group) when between 10 and 16 weeks pregnant to either to the 44 session gFNP program or to standard care after the collection of baseline information. Researchers are blind to group assignment. The primary outcomes at 12 months are child abuse potential based on the revised Adult-Adolescent Parenting Inventory and parent/infant interaction coded using the CARE Index based on a video-taped interaction. Secondary outcomes are maternal depression, parenting stress, health related quality of life, social support, and use of services.

Discussion: This is the first study of the effectiveness of gFNP in the UK. Results should inform decision-making about its delivery alongside universal services, potentially enabling a wider range of families to benefit from the FNP curriculum and approach to supporting parenting.

From North Africa to France:Family Migration in Text and Film

Over the past four decades immigration to France from the Francophone countries of North Africa has changed in character. For much of the twentieth century, migrants who crossed the Mediterranean to France were men seeking work, who frequently undertook manual labour, working long hours in difficult conditions. Recent decades have seen an increase in family reunification - the arrival of women and children from North Africa, either accompanying their husbands or joining them in France. Contemporary creative representations of migration are shaped by this shift in gender and generation from a solitary, mostly male experience to one that included women and children. Just as the shift made new demands of the 'host' society, it made new demands of authors and filmmakers as they seek to represent migration. This study reveals how text and film present new ways of thinking about migration, moving away from the configuration of the migrant as man and worker, to take women, children and the ties between them into account.

Thermal properties, sizes, and size distribution of Jupiter-family cometary nuclei

We present results from SEPPCoN, an on-going Survey of the Ensemble Physical Properties of Cometary Nuclei. In this report we discuss mid-infrared measurements of the thermal emission from 89 nuclei of Jupiter-family comets (JFCs). All data were obtained in 2006 and 2007 using imaging capabilities of the Spitzer Space Telescope. The comets were typically 4-5 AU from the Sun when observed and most showed only a point-source with little or no extended emission from dust. For those comets showing dust, we used image processing to photometrically extract the nuclei. For all 89 comets, we present new effective radii, and for 57 comets we present beaming parameters. Thus our survey provides the largest compilation of radiometrically-derived physical properties of nuclei to date. We have six main conclusions: (a) The average beaming parameter of the JFC population is 1.03 ± 0.11, consistent with unity; coupled with the large distance of the nuclei from the Sun, this indicates that most nuclei have Tempel 1-like thermal inertia. Only two of the 57 nuclei had outlying values (in a statistical sense) of infrared beaming. (b) The known JFC population is not complete even at 3 km radius, and even for comets that approach to ˜2 AU from the Sun and so ought to be more discoverable. Several recently-discovered comets in our survey have small perihelia and large (above ˜2 km) radii. (c) With our radii, we derive an independent estimate of the JFC nuclear cumulative size distribution (CSD), and we find that it has a power-law slope of around -1.9, with the exact value depending on the bounds in radius. (d) This power-law is close to that derived by others from visible-wavelength observations that assume a fixed geometric albedo, suggesting that there is no strong dependence of geometric albedo with radius. (e) The observed CSD shows a hint of structure with an excess of comets with radii 3-6 km. (f) Our CSD is consistent with the idea that the intrinsic size distribution of the JFC population is not a simple power-law and lacks many sub-kilometer objects.

Psychosocial, educational and communicative interventions for patients with cachexia and their family carers

Purpose of review: Cancer cachexia has a substantial impact on both patients and their family carers. It has been acknowledged as one of the two most frequent and devastating problems of advanced cancer. The impact of cachexia spans biopsychosocial realms. Symptom management in cachexia is fraught with difficulties and globally, there remains no agreed standard care or treatment for this client group. There is a need to address the psychosocial impact of cachexia for both patients and their family carers.

Recent findings: Patients living at home and their family carers are often left to manage the distressing psychosocial impacts of cancer cachexia themselves. Successful symptom management requires healthcare professionals to address the holistic impact of cancer cachexia. High quality and rigorous research details the existential impact of cachexia on patients and their family carers. This information needs to inform psychosocial, educational and communicative supportive healthcare interventions to help both patients and their family carers better cope with the effects of cachexia.

Summary: Supportive interventions need to inform both patients and their family carers of the expected impacts of cachexia, and address how to cope with them to retain a functional, supported family unit who are informed about and equipped to care for a loved one with cachexia.

Using CAD parameter sensitivities for stack-up tolerance allocation

Tolerance allocation is an important step in the design process. It is necessary to produce high quality components cost-effectively. However, the process of allocating tolerances can be time consuming and difficult, especially for complex models. This work demonstrates a novel CAD based approach, where the sensitivities of product dimensions to changes in the values of the feature parameters in the CAD model are computed. These are used to automatically establish the assembly response function for the product. This information has been used to automatically allocate tolerances to individual part dimensions to achieve specified tolerances on the assembly dimensions, even for tolerance allocation in more than one direction simultaneously. It is also shown how pre-existing constraints on some of the part dimensions can be represented and how situations can be identified where the required tolerance allocation is not achievable. A methodology is also presented that uses the same information to model a component with different amounts of dimensional variation to simulate the effects of tolerance stack-up. © 2014 Springer-Verlag France.

When terror hits home: Identity Fused Americans who saw Boston bombing victims as “family” provided aid

When tragedy strikes a group, only some group members characteristically rush to the aid of the victims. What motivates the altruism of these exceptional individuals? Here, we provide one set of answers based on data collected before and shortly after the 15 April 2013, Boston Marathon bombings. The results of three studies indicated that Americans who were strongly “fused” with their country were especially inclined to provide various forms of support to the bombing victims. Moreover, the degree to which participants reported perceiving fellow Americans as psychological kin statistically mediated links between fusion and pro-group outcomes. Together, these findings shed new light on relationships between personal and group identity, cognitive representations of group members, and personally costly, pro-group actions.

Exploring molecular recognition pathways in one- and two-component gels formed by dendritic lysine-based gelators

This paper provides an integrated overview of the factors which control gelation in a family of dendritic gelators based on lysine building blocks. In particular, we establish that higher generation systems are more effective gelators, amide linkages in the dendron are better than carbamates, and long alkyl chain surface groups and a carboxylic acid at the focal point enhance gelation. The gels are best formed in relatively low polarity solvents with no hydrogen bond donor ability and limited hydrogen bond acceptor capacity. The dendrons with acid groups at the focal point can form two component gels with diaminododecane, and in this case, it is the lower generation dendrons which can avoid steric hindrance and form more effective gels. The stereochemistry of lysine is crucial in self-assembly, with opposite enantiomers disrupting each other's molecular recognition pathways. For the two-component system, stoichiometry is key, if too much diamine is present, dendron-stabilised microcrystals of the diamine begin to form. Interestingly, gelation still occurs in this case, and the systems with amides/alkyl chains are more effective gels, as a consequence of enhanced dendron-dendron intermolecular interactions allowing the microcrystals to form an interconnected network.

Exploring molecular recognition pathways within a family of gelators with different hydrogen bonding motifs

We report the synthesis of a family of gelators in which alkyl chains are connected to the amino groups of L-lysine methyl ester using a range of different hydrogen bonding linking groups (carbamate, amide, urea, thiourea and diacylhydrazine) using simple synthetic methodology based on isocyanate or acid chloride chemistry. The ability of these compounds to gelate organic solvents such as toluene or cyclohexane can be directly related to the ability of the linking group to form intermolecular hydrogen bonds. In general terms, the ability to structure solvents can be considered as: thiourea <carbamate <amide <urea similar to diacylhydrazine. This process has been confirmed by thermal measurements, scanning electron microscopy (SEM) and infrared and circular dichroism spectroscopies. By deprotecting the methyl ester group, we have demonstrated that a balance between hydrophobic and hydrophilic groups is essential-if the system has too much hydrophilicity (e. g., diacylhydrazine, urea) it will not form gels due to low solubility in the organic media. However, the less effective gelators based on amide and carbamate linkages are enhanced by converting the methyl ester to a carboxylic acid. Furthermore, subsequent mixing of the acid with a second component (diaminododecane) further enhances the ability to form networks, and, in the case of the amide, generates a two-component gel, which can immobilise a wide range of solvents of industrial interest including petrol and diesel (fuel oils), olive oil and sunflower oil (renewable food oils) and ethyl laurate, isopropyl myristate and isopropyl palmitate (oils used in pharmaceutical formulation). The gels are all thermoreversible, and may therefore be useful in controlled release/formulation applications.

Family-based associations in measures of psychological distress and quality of life in a cardiac screening clinic for inheritable cardiac diseases: a cross-sectional study

BACKGROUND: Family-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic.

METHODS: Prospective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data.

RESULTS: There was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance.

CONCLUSIONS: High levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has implications for family screening and intervention programmes.

Comparative biochemical analysis of three members of the Schistosoma mansoni TAL family: Differences in ion and drug binding properties

The tegumental allergen-like (TAL) proteins from Schistosoma mansoni are part of a family of calcium binding proteins found only in parasitic flatworms. These proteins have attracted interest as potential drug or vaccine targets, yet comparatively little is known about their biochemistry. Here, we compared the biochemical properties of three members of this family: SmTAL1 (Sm22.6), SmTAL2 (Sm21.7) and SmTAL3 (Sm20.8). Molecular modelling suggested that, despite similarities in domain organisation, there are differences in the three proteins’ structures. SmTAL1 was predicted to have two functional calcium binding sites and SmTAL2 was predicted to have one. Despite the presence of two EF-hand-like structures in SmTAL3, neither was predicted to be functional. These predictions were confirmed by native gel electrophoresis, intrinsic fluorescence and differential scanning fluorimetry: both SmTAL1 and SmTAL2 are able to bind calcium ions reversibly, but SmTAL3 is not. SmTAL1 is also able to interact with manganese, strontium, iron(II) and nickel ions. SmTAL2 has a different ion binding profile interacting with cadmium, manganese, magnesium, strontium and barium ions in addition to calcium. All three proteins form dimers and, in contrast to some Fasciola hepatica proteins from the same family; dimerization is not affected by calcium ions. SmTAL1 interacts with the anti-schistosomal drug praziquantel and the calmodulin antagonists trifluoperazine, chlorpromazine and W7. SmTAL2 interacts only with W7. SmTAL3 interacts with the aforementioned calmodulin antagonists and thiamylal, but not praziquantel. Overall, these data suggest that the proteins have different biochemical properties and thus, most likely, different in vivo functions.

Improving parameter learning of Bayesian nets from incomplete data

This paper addresses the estimation of parameters of a Bayesian network from incomplete data. The task is usually tackled by running the Expectation-Maximization (EM) algorithm several times in order to obtain a high log-likelihood estimate. We argue that choosing the maximum log-likelihood estimate (as well as the maximum penalized log-likelihood and the maximum a posteriori estimate) has severe drawbacks, being affected both by overfitting and model uncertainty. Two ideas are discussed to overcome these issues: a maximum entropy approach and a Bayesian model averaging approach. Both ideas can be easily applied on top of EM, while the entropy idea can be also implemented in a more sophisticated way, through a dedicated non-linear solver. A vast set of experiments shows that these ideas produce significantly better estimates and inferences than the traditional and widely used maximum (penalized) log-likelihood and maximum a posteriori estimates. In particular, if EM is adopted as optimization engine, the model averaging approach is the best performing one; its performance is matched by the entropy approach when implemented using the non-linear solver. The results suggest that the applicability of these ideas is immediate (they are easy to implement and to integrate in currently available inference engines) and that they constitute a better way to learn Bayesian network parameters.

One size fits all: stability of metabolic scaling under warming and ocean acidification in echinoderms

Responses by marine species to ocean acidification (OA) have recently been shown to be modulated by external factors including temperature, food supply and salinity. However the role of a fundamental biological parameter relevant to all organisms, that of body size, in governing responses to multiple stressors has been almost entirely overlooked. Recent consensus suggests allometric scaling of metabolism with body size differs between species, the commonly cited 'universal' mass scaling exponent (b) of A3/4 representing an average of exponents that naturally vary. One model, the Metabolic-Level Boundaries hypothesis, provides a testable prediction: that b will decrease within species under increasing temperature. However, no previous studies have examined how metabolic scaling may be directly affected by OA. We acclimated a wide body-mass range of three common NE Atlantic echinoderms (the sea star Asterias rubens, the brittlestars Ophiothrix fragilis and Amphiura filiformis) to two levels of pCO(2) and three temperatures, and metabolic rates were determined using closed-chamber respirometry. The results show that contrary to some models these echinoderm species possess a notable degree of stability in metabolic scaling under different abiotic conditions; the mass scaling exponent (b) varied in value between species, but not within species under different conditions. Additionally, we found no effect of OA on metabolic rates in any species. These data suggest responses to abiotic stressors are not modulated by body size in these species, as reflected in the stability of the metabolic scaling relationship. Such equivalence in response across ontogenetic size ranges has important implications for the stability of ecological food webs.

Family Economic Vulnerability & the Great Recession: An Analysis of the First two Waves of the Growing Up in Ireland Study

In this paper we make use of the first and second waves of the 2008 and 1998 cohorts of the Growing Up in Ireland study, to develop a multidimensional and dynamic approach to understanding the impact on families and children in Ireland of the Great Recession. Economic vulnerability is operationalised as involving a distinctive risk profile in relation to relative income, household joblessness and economic stress. We find that the recession was associated with a significant increase in levels of economic vulnerability and changing risk profiles involving a more prominent role for economic stress for both the 2008 and 1998 cohorts. The factors affecting vulnerability outcomes were broadly similar for both cohorts. Persistent economic vulnerability was significantly associated with lone parenthood, particularly for those with more than one child, lower levels of Primary Care Giver (PCG) education and to a lesser extent younger age of PCG at child’s birth, number of children and a parent leaving or dying. Similar factors were associated with transient vulnerability in the first wave but the magnitude of the effects was significantly weaker particularly in relation to lone parenthood and level of education of the PCG. For entry into vulnerability the impact of these factors was again substantially weaker than for persistent and transient vulnerability indicating a significantly greater degree of socio-economic heterogeneity among the group that became vulnerable during the recession. The findings raise policy and political problems that go beyond those associated with catering for groups that have tended to be characterized by high dependence on social welfare.

One-Electron Reduction of 2-Nitrotoluene, Nitrocyclopentane, and 1-Nitrobutane in Room Temperature Ionic Liquids: A Comparative Study of Butler–Volmer and Symmetric Marcus–Hush Theories Using Microdisk Electrodes

The voltammetry for the reduction of 2-nitrotoluene at a gold microdisk electrode is reported in two ionic liquids: trihexyltetradecylphosphonium tris(pentafluoroethyl)trifluorophosphate ([P-14,P-6,P-6,P-6][FAP]) and 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([Emim][NTf2]). The reduction of nitrocyclopentane (NCP) and 1-nitrobutane (BuN) was investigated using voltammetry at a gold microdisk electrode in the ionic liquid [P-14,P-6,P-6,P-6][FAP]. Simulated voltammograms, generated through the use of ButlerVolmer theory and symmetric MarcusHush theory, were compared to experimental data, with both theories parametrizing the data similarly well. An experimental value for the Marcusian parameter, 1 was also determined in all cases. For the reduction of 2-nitrotoluene, this was 0.5 +/- 0.1 eV in both solvents, while for NCP and BuN in [P-14,P-6,P-6,P-6][FAP], it was 2 +/- 0.1 and 5 +/- 0.1 eV, respectively. This is attributed to the localization of charge on the nitro group and the primary nitro alkyls increased interaction with the environment, resulting in a larger reorganization energy.