Family connections versus optimised treatment-as-usual for family members of individuals with borderline personality disorder: non-randomised controlled study

Background: Borderline personality disorder (BPD) is challenging for family members who are often required to fulfil multiple roles such as those of advocate, caregiver, coach and guardian. To date, two uncontrolled studies by the treatment developers suggest that Family Connections (FC) is an effective programme to support, educate and teach skills to family members of individuals with BPD. However, such studies have been limited by lack of comparison to other treatment approaches. This study aimed to compare the effectiveness of FC with an optimised treatment-as-usual (OTAU) programme for family members of individuals with BPD. A secondary aim was to introduce a long term follow-up to investigate if positive gains from the intervention would be maintained following programme completion. Methods: This study was a non-randomised controlled study, with assessment of outcomes at baseline (pre-intervention) and end of programme (post-intervention) for both FC and OTAU groups, and at follow-up (3 months post-intervention; 12 or 19 months post-intervention) for the FC group. Eighty family members participated in the FC (n = 51) and the OTAU (n = 29) programmes. Outcome measures included burden, grief, depression and mastery. Linear mixed-effects models were used to assess baseline differences in the outcome measures by gender, age group and type of relationship to the individual with BPD. Linear mixed-effects models were also used to estimate the treatment effect (FC versus OTAU) utilising all available data from baseline and end of programme. Results: The FC group showed changes indicating significant improvement with respect to all four outcome measures (p < 0.001). The OTAU group showed changes in the same direction as the intervention group but none of the changes were statistically significant. The intervention effect was statistically significant for total burden (including both subscales; p = .02 for subjective burden and p = .048 for objective burden) and grief (p = 0.013). Improvements were maintained at follow-up for FC participants. Conclusions: The findings of the current study indicate that FC results in statistically significant improvements on key measures while OTAU does not yield comparable changes. Lack of significant change on all measures for OTAU suggests that a three session psycho-education programme is of limited benefit. Further research is warranted on programme components and long-term supports for family members

Ultrametric spaces of branches on arborescent singularities

Let $S$ be a normal complex analytic surface singularity. We say that $S$ is arborescent if the dual graph of any resolution of it is a tree. Whenever $A,B$ are distinct branches on $S$, we denote by $A \cdot B$ their intersection number in the sense of Mumford. If $L$ is a fixed branch, we define $U_L(A,B)= (L \cdot A)(L \cdot B)(A \cdot B)^{-1}$ when $A \neq B$ and $U_L(A,A) =0$ otherwise. We generalize a theorem of P{\l}oski concerning smooth germs of surfaces, by proving that whenever $S$ is arborescent, then $U_L$ is an ultrametric on the set of branches of $S$ different from $L$. We compute the maximum of $U_L$, which gives an analog of a theorem of Teissier. We show that $U_L$ encodes topological information about the structure of the embedded resolutions of any finite set of branches. This generalizes a theorem of Favre and Jonsson concerning the case when both $S$ and $L$ are smooth. We generalize also from smooth germs to arbitrary arborescent ones their valuative interpretation of the dual trees of the resolutions of $S$. Our proofs are based in an essential way on a determinantal identity of Eisenbud and Neumann.Comment: 37 pages, 16 figures. Compared to the first version on Arxiv, il has a new section 4.3, accompanied by 2 new figures. Several passages were clarified and the typos discovered in the meantime were correcte

Intermittent control models of human standing: similarities and differences

Two architectures of intermittent control are compared and contrasted in the context of the single inverted pendulum model often used for describing standing in humans. The architectures are similar insofar as they use periods of open-loop control punctuated by switching events when crossing a switching surface to keep the system state trajectories close to trajectories leading to equilibrium. The architectures differ in two significant ways. Firstly, in one case, the open-loop control trajectory is generated by a system-matched hold, and in the other case, the open-loop control signal is zero. Secondly, prediction is used in one case but not the other. The former difference is examined in this paper. The zero control alternative leads to periodic oscillations associated with limit cycles; whereas the system-matched control alternative gives trajectories (including homoclinic orbits) which contain the equilibrium point and do not have oscillatory behaviour. Despite this difference in behaviour, it is further shown that behaviour can appear similar when either the system is perturbed by additive noise or the system-matched trajectory generation is perturbed. The purpose of the research is to come to a common approach for understanding the theoretical properties of the two alternatives with the twin aims of choosing which provides the best explanation of current experimental data (which may not, by itself, distinguish beween the two alternatives) and suggesting future experiments to distinguish between the two alternatives

Kikuchi-Fujimoto disease

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disorder, characterized by regional cervical lymphadenopathy with tenderness, usually accompanied with mild fever and night sweats. Less frequent symptoms include weight loss, nausea, vomiting, sore throat. Kikuchi-Fujimoto disease is an extremely rare disease known to have a worldwide distribution with higher prevalence among Japanese and other Asiatic individuals. The clinical, histopathological and immunohistochemical features appear to point to a viral etiology, a hypothesis that still has not been proven. KFD is generally diagnosed on the basis of an excisional biopsy of affected lymph nodes. Its recognition is crucial especially because this disease can be mistaken for systemic lupus erythematosus, malignant lymphoma or even, though rarely, for adenocarcinoma. Clinicians' and pathologists' awareness of this disorder may help prevent misdiagnsois and inappropriate treatment. The diagnosis of KFD merits active consideration in any nodal biopsy showing fragmentation, necrosis and karyorrhexis, especially in young individuals presenting with posterior cervical lymphadenopathy. Treatment is symptomatic (analgesics-antipyretics, non-steroidal anti-inflammatory drugs and, rarely, corticosteroids). Spontaneous recovery occurs in 1 to 4 months. Patients with Kikuchi-Fujimoto disease should be followed-up for several years to survey the possibility of the development of systemic lupus erythematosus

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

Unravelling the effects of age, period and cohort on metabolic syndrome components in a Taiwanese population using partial least squares regression

<p>Abstract</p> <p>Background</p> <p>We investigate whether the changing environment caused by rapid economic growth yielded differential effects for successive Taiwanese generations on 8 components of metabolic syndrome (MetS): body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), triglycerides (TG), high-density lipoprotein (HDL), Low-density lipoproteins (LDL) and uric acid (UA).</p> <p>Methods</p> <p>To assess the impact of age, birth year and year of examination on MetS components, we used partial least squares regression to analyze data collected by Mei-Jaw clinics in Taiwan in years 1996 and 2006. Confounders, such as the number of years in formal education, alcohol intake, smoking history status, and betel-nut chewing were adjusted for.</p> <p>Results</p> <p>As the age of individuals increased, the values of components generally increased except for UA. Men born after 1970 had lower FPG, lower BMI, lower DBP, lower TG, Lower LDL and greater HDL; women born after 1970 had lower BMI, lower DBP, lower TG, Lower LDL and greater HDL and UA. There is a similar pattern between the trend in levels of metabolic syndrome components against birth year of birth and economic growth in Taiwan.</p> <p>Conclusions</p> <p>We found cohort effects in some MetS components, suggesting associations between the changing environment and health outcomes in later life. This ecological association is worthy of further investigation.</p

Introduction of Solid Food to Young Infants

Timing of the first introduction of solid food during infancy may have potential effects on life-long health. To understand the characteristics that are associated with the timing of infants’ initial exposure to solid foods. The 2000 National Survey of Early Childhood Health (NSECH) was a nationally representative telephone survey of 2,068 parents of children aged 4–35 months, which profiled content and quality of health care for young children. African-American and Latino families were over-sampled. Analyses in this report include bivariate tests and logistic regressions. 62% of parents reported introducing solids to their child between 4–6 months of age. African-American mothers (OR = 0.5 [0.3, 0.9]), English-speaking Latino mothers (OR = 0.4 [0.2, 0.7]), White mothers with more than high school education (OR = 0.5 [0.2, 1.0]), and mothers who breastfed for 4 months or longer (OR = 0.4 [0.3, 0.7]) were less likely to introduce solids early. Most parents (92%) of children 4–9 months of age reported that their pediatric provider had discussed introduction of solids with them since the child’s birth, and provider discussion of feeding was not associated with the timing of introduction of solids. Although most parents recall discussing the introduction of solid foods with their child’s physician, several subgroups of mothers introduce solid foods earlier than the AAP recommendation of 4–6 months. More effective discussion of solid food introduction linked to counseling and support of breastfeeding by the primary health care provider may reduce early introduction of solids

Crystal Structure of the RNA Recognition Motif of Yeast Translation Initiation Factor eIF3b Reveals Differences to Human eIF3b

BACKGROUND: The multi-subunit eukaryotic initiation factor3 (eIF3) plays a central role in the initiation step of protein synthesis in eukaryotes. One of its large subunits, eIF3b, serves as a scaffold within eIF3 as it interacts with several other subunits. It harbors an RNA Recognition Motif (RRM), which is shown to be a non-canonical RRM in human as it is not capable to interact with oligonucleotides, but rather interacts with eIF3j, a sub-stoichiometric subunit of eIF3. PRINCIPAL FINDING: We have analyzed the high-resolution crystal structure of the eIF3b RRM domain from yeast. It exhibits the same fold as its human ortholog, with similar charge distribution on the surface interacting with the eIF3j in human. Thermodynamic analysis of the interaction between yeast eIF3b-RRM and eIF3j revealed the same range of enthalpy change and dissociation constant as for the human proteins, providing another line of evidence for the same mode of interaction between eIF3b and eIF3j in both organisms. However, analysis of the surface charge distribution of the putative RNA-binding β-sheet suggested that in contrast to its human ortholog, it potentially could bind oligonucleotides. Three-dimensional positioning of the so called "RNP1" motif in this domain is similar to other canonical RRMs, suggesting that this domain might indeed be a canonical RRM, conferring oligonucleotide binding capability to eIF3 in yeast. Interaction studies with yeast total RNA extract confirmed the proposed RNA binding activity of yeast eIF3b-RRM. CONCLUSION: We showed that yeast eIF3b-RRM interacts with eIF3j in a manner similar to its human ortholog. However, it shows similarities in the oligonucleotide binding surface to canonical RRMs and interacts with yeast total RNA. The proposed RNA binding activity of eIF3b-RRM may help eIF3 to either bind to the ribosome or recruit the mRNA to the 43S pre-initiation complex

Pyroglutamate Abeta pathology in APP/PS1KI mice, sporadic and familial Alzheimer’s disease cases

The presence of AβpE3 (N-terminal truncated Aβ starting with pyroglutamate) in Alzheimer’s disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Aβ peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down’s syndrome postmortem brain tissue. Importantly, AβpE3 has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Aβ. We have recently shown that intraneuronal accumulation of AβpE3 peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in AβpE3, we have generated two novel monoclonal antibodies which were characterized as highly specific for AβpE3 peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for AβpE3 were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly, in APP/PS1KI mice we observed a continuous increase in AβpE3 plaque load with increasing age, while the density for Aβ1-x plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of Aβ are N-truncated as disease progresses, and that, AβpE3 positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate

A combined model reduction algorithm for controlled biochemical systems

Background: Systems Biology continues to produce increasingly large models of complex biochemical reaction networks. In applications requiring, for example, parameter estimation, the use of agent-based modelling approaches, or real-time simulation, this growing model complexity can present a significant hurdle. Often, however, not all portions of a model are of equal interest in a given setting. In such situations methods of model reduction offer one possible approach for addressing the issue of complexity by seeking to eliminate those portions of a pathway that can be shown to have the least effect upon the properties of interest. Methods: In this paper a model reduction algorithm bringing together the complementary aspects of proper lumping and empirical balanced truncation is presented. Additional contributions include the development of a criterion for the selection of state-variable elimination via conservation analysis and use of an ‘averaged’ lumping inverse. This combined algorithm is highly automatable and of particular applicability in the context of ‘controlled’ biochemical networks. Results: The algorithm is demonstrated here via application to two examples; an 11 dimensional model of bacterial chemotaxis in Escherichia coli and a 99 dimensional model of extracellular regulatory kinase activation (ERK) mediated via the epidermal growth factor (EGF) and nerve growth factor (NGF) receptor pathways. In the case of the chemotaxis model the algorithm was able to reduce the model to 2 state-variables producing a maximal relative error between the dynamics of the original and reduced models of only 2.8% whilst yielding a 26 fold speed up in simulation time. For the ERK activation model the algorithm was able to reduce the system to 7 state-variables, incurring a maximal relative error of 4.8%, and producing an approximately 10 fold speed up in the rate of simulation. Indices of controllability and observability are additionally developed and demonstrated throughout the paper. These provide insight into the relative importance of individual reactants in mediating a biochemical system’s input-output response even for highly complex networks. Conclusions: Through application, this paper demonstrates that combined model reduction methods can produce a significant simplification of complex Systems Biology models whilst retaining a high degree of predictive accuracy. In particular, it is shown that by combining the methods of proper lumping and empirical balanced truncation it is often possible to produce more accurate reductions than can be obtained by the use of either method in isolation