Impact of an Interdisciplinary Deep Brain Stimulation Screening Model on Post-Surgical Complications in Essential Tremor Patients

Objective

To investigate the relationship of our interdisciplinary screening process on post-operative unintended hospitalizations and quality of life.

Background

There are currently no standardized criteria for selection of appropriate Deep Brain Stimulation candidates and little hard data exists to support the use of any singular method.

Methods

An Essential Tremor cohort was selected from our institutional Deep Brain Stimulation database. The interdisciplinary model utilized seven specialties who pre-operatively screened all potential Deep Brain Stimulation candidates. Concerns for surgery raised by each specialty were documented and classified as none, minor, or major. Charts were reviewed to identify unintended hospitalizations and quality of life measurements at 1 year post-surgery.

Results

Eighty-six percent (44/51) of the potential screened candidates were approved for Deep Brain Stimulation. Eight (18%) patients had an unintended hospitalization during the follow-up period. Patients with minor or major concerns raised by any specialty service had significantly more unintended hospitalizations when compared to patients without concerns (75% vs. 25%, p < 0.005). The rate of hospitalization revealed a direct relationship to the “level of concern”; ranging from 100% if major concerns, 42% if minor concerns, and 7% if no concerns raised, p = 0.001. Quality of life scores significantly worsened in patients with unintended hospitalizations at 6 (p = 0.046) and 12 months (p = 0.027) when compared to baseline scores. No significant differences in tremor scores between unintended and non-unintended hospitalizations were observed.

Conclusions

The number and level of concerns raised during interdisciplinary Deep Brain Stimulation screenings were significantly related to unintended hospitalizations and to a reduced quality of life. The interdisciplinary evaluation may help to stratify risk for these complications. However, data should be interpreted with caution due to the limitations of our study. Further prospective comparative and larger studies are required to confirm our results.     

Stand-Alone Personalized Normative Feedback for College Student Drinkers: A Meta-Analytic Review, 2004 to 2014

Background

Norms clarification has been identified as an effective component of college student drinking interventions, prompting research on norms clarification as a single-component intervention known as Personalized Normative Feedback (PNF). Previous reviews have examined PNF in combination with other components but not as a stand-alone intervention.

Objectives

To investigate the degree to which computer-delivered stand-alone personalized normative feedback interventions reduce alcohol consumption and alcohol-related harms among college students and to compare gender-neutral and gender-specific PNF.

Data Sources

Electronic databases were searched systematically through November 2014. Reference lists were reviewed manually and forward and backward searches were conducted.

Selection Criteria

Outcome studies that compared computer-delivered, stand-alone PNF intervention with an assessment only, attention-matched, or active treatment control and reported alcohol use and harms among college students.

Methods

Between-group effect sizes were calculated as the standardized mean difference in change scores between treatment and control groups divided by pooled standard deviation. Within-group effect sizes were calculated as the raw mean difference between baseline and follow-up divided by pooled within-groups standard deviation.

Results

Eight studies (13 interventions) with a total of 2,050 participants were included. Compared to control participants, students who received gender-neutral (d _between = 0.291, 95% CI [0.159, 0.423]) and gender-specific PNF (d _between = 0.284, 95% CI [0.117, 0.451]) reported greater reductions in drinking from baseline to follow-up. Students who received gender-neutral PNF reported 3.027 (95% CI [2.171, 3.882]) fewer drinks per week at first follow-up and gender-specific PNF reported 3.089 (95% CI [0.992, 5.186]) fewer drinks. Intervention effects were small for harms (d _between = 0.157, 95% CI [0.037, 0.278]).

Conclusions

Computer-delivered PNF is an effective stand-alone approach for reducing college student drinking and has a small impact on alcohol-related harms. Effects are small but clinically relevant when considered from a public health perspective. Additional research is needed to examine computer-delivered, stand-alone PNF as a population-level prevention program.     

Chromosomal Evolution and Patterns of Introgression in Helianthus

Knowledge of the nature and extent of karyotypic differences between species provides insight into the evolutionary history of the genomes in question and, in the case of closely related species, the potential for genetic exchange between taxa. We constructed high-density genetic maps of the silverleaf sunflower (Helianthus argophyllus) and Algodones Dune sunflower (H. niveus ssp. tephrodes) genomes and compared them to a consensus map of cultivated sunflower (H. annuus) to identify chromosomal rearrangements between species. The genetic maps of H. argophyllus and H. niveus ssp. tephrodes included 17 linkage groups each and spanned 1337 and 1478 cM, respectively. Comparative analyses revealed greater divergence between H. annuus and H. niveus ssp. tephrodes (13 inverted segments, 18 translocated segments) than between H. annuus and H. argophyllus (10 inverted segments, 8 translocated segments), consistent with their known phylogenetic relationships. Marker order was conserved across much of the genome, with 83 and 64% of the H. argophyllus and H. niveus ssp. tephrodes genomes, respectively, being syntenic with H. annuus. Population genomic analyses between H. annuus and H. argophyllus, which are sympatric across a portion of the natural range of H. annuus, revealed significantly elevated genetic structure in rearranged portions of the genome, indicating that such rearrangements are associated with restricted gene flow between these two species.     

Identification, characterization, and expression of a unique secretory lipase from the human pathogen Leishmania donovani

Lipases have been implicated to be of importance in the life cycle development, virulence, and transmission of a variety of parasitic organisms. Potential functions include the acquisition of host resources for energy metabolism and as simple building blocks for the synthesis of complex parasite lipids important for membrane remodeling and structural purposes. Using a molecular approach, we identified and characterized the structure of an LdLip3-lipase gene from the primitive trypanosomatid pathogen of humans, Leishmania donovani. The LdLip3 encodes a ~33 kDa protein, with a well-conserved substrate-binding and catalytic domains characteristic of members of the serine lipase-protein family. Further, we showed that LdLip3 mRNA is constitutively expressed by both the insect vector (i.e., promastigote) and mammalian (i.e., amastigote) life cycle developmental forms of this protozoan parasite. Moreover, a homologous episomal expression system was used to express an HA epitope-tagged LdLip3 chimeric construct (LdLip3::HA) in these parasites. Expression of the LdLip3 chimera was verified in these transfectants by Western blots and indirect immuno-fluorescence analyses. Results of coupled immuno-affinity purification and enzyme activity experiments demonstrated that the LdLip3::HA chimeric protein was secreted/released by transfected L. donovani parasites and that it possessed functional lipase enzyme activity. Taken together these observations suggest that this novel secretory lipase might play essential role(s) in the survival, growth, and development of this important group of human pathogens.     

Owlifier: Creating OWL-DL ontologies from simple spreadsheet-based knowledge descriptions

Discovery and integration of data is important in many ecological studies, especially those that concern broad-scale ecological questions. Data discovery and integration are often difficult and time consuming tasks for researchers, which is due in part to the use of informal, ambiguous, and sometimes inconsistent terms for describing data content. Ontologies offer a solution to this problem by providing consistent definitions of ecological concepts that in turn can be used to annotate, relate, and search for data sets. However, unlike in molecular biology or biomedicine, few ontology development efforts exist within ecology. Ontology development often requires considerable expertise in ontology languages and development tools, which is often a barrier for ontology creation in ecology. In this paper we describe an approach for ontology creation that allows ecologists to use common spreadsheet tools to describe different aspects of an ontology. We present conventions for creating, relating, and constraining concepts through spreadsheets, and provide software tools for converting these ontologies into equivalent OWL-DL representations. We also consider inverse translations, i.e., to convert ontologies represented using OWL-DL into our spreadsheet format. Our approach allows large lists of terms to be easily related and organized into concept hierarchies, and generally provides a more intuitive and natural interface for ontology development by ecologists.     

The effects of P2X7 receptor antagonists on the formation and function of human osteoclasts in vitro

The P2X7 receptor (P2X7R) has been implicated in the process of multinucleation and cell fusion. We have previously demonstrated that blockade of P2X7Rs on osteoclast precursors using a blocking antibody inhibited multinucleated osteoclast formation in vitro, but that P2X7R KO mice maintain the ability to form multinucleated osteoclasts. This apparent contradiction of the role the P2X7R plays in multinucleation has prompted us to examine the effect of the most commonly used and recently available P2X7R antagonists on osteoclast formation and function. When added to recombinant RANKL and M-CSF human blood monocytes cultures, all but one compound, decreased the formation and function of multinucleated TRAP-positive osteoclasts in a concentration-dependent manner. These data provide further evidence for the role of the P2X7R in the formation of functional human multinucleated osteoclasts and highlight the importance of selection of antagonists for use in long-term experiments.     

The adaptive dynamics of the evolution of host resistance to indirectly transmitted microparasites

We use adaptive dynamics and pairwise invadability plots to examine the evolutionary dynamics of host resistance to microparasitic infection transmitted indirectly via free stages. We investigate trade-offs between pathogen transmission rate and intrinsic growth rate. Adaptive dynamics distinguishes various evolutionary outcomes associated with repellors, attractors or branching points. We find criteria corresponding to these and demonstrate that a major factor deciding the evolutionary outcome is whether trade-offs are acceleratingly or deceleratingly costly. We compare and contrast two models and show how the differences between them lead to different evolutionary outcomes.     

Dynamics of infection with multiple transmission mechanisms in unmanaged/managed animal populations

Deterministic and stochastic models motivated by Salmonella transmission in unmanaged/managed populations are studied. The SIRS models incorporate three routes of transmission (direct, vertical and indirect via free-living infectious units in the environment). With deterministic models we are able to understand the effects of different routes of transmission and other epidemiological factors on infection dynamics. In particular, vertical transmission has little influence on this dynamics, whereas the higher the indirect (direct) transmission rate the greater the tendency to persistent oscillation (stable endemic states). We show that the sustained cycles are also prone to demographic effect, i.e., persistent oscillation becomes impossible in the managed case (in the sense of balanced recruitment and death rates) by comparing with results in unmanaged populations (exponential population dynamics). Further, approximations of quasi-stationary distributions are derived for stochastic versions of the proposed models based on a diffusion approximation to the infection process. The effect of transmission parameters on the ratio of mean to standard deviation of the approximating distribution, used to judge the validity of the approximations and the expected time until fade out of infection, is further discussed. We conclude that strengthening any route of transmission may or may not reduce the expected time to fade out of infection, depending on the population dynamics.     

Pair approximations and the inclusion of indirect transmission: theory and application to between farm transmission of Salmonella

The spatial-temporal dynamics of farm animal diseases depend both on disease specific processes and the underlying contact network between farms. Indirect transmission via free-living bacteria in the environment is an important transmission route and contributes significantly to the dynamics. The pair-wise model has been developed to include both direct transmission and indirect transmission via free stages. The model is compared with stochastic simulations of epidemics on contact networks. The network framework is applied to the investigation of the epidemiological dynamics of between-herd transmission of Salmonella spp. The main results help to explain differences in observed epidemiological patterns and to identify possible causes for different strains of Salmonella developing so much variation in their infection dynamics in UK dairy herds. Numerical results show that shorter infectious period, more persistent immune response and more rapid removal of faeces result in a lower prevalence of infection and a greater tendency for (damped) oscillation. A possible control strategy is consequently suggested. Furthermore, the effect of network structure on long-term dynamics is examined.     

Loss-of-function mutations in growth differentiation factor-1 (GDF1) are associated with congenital heart defects in humans

Congenital heart defects (CHDs) are among the most common birth defects in humans (incidence 8-10 per 1,000 live births). Although their etiology is often poorly understood, most are considered to arise from multifactorial influences, including environmental and genetic components, as well as from less common syndromic forms. We hypothesized that disturbances in left-right patterning could contribute to the pathogenesis of selected cardiac defects by interfering with the extrinsic cues leading to the proper looping and vessel remodeling of the normally asymmetrically developed heart and vessels. Here, we show that heterozygous loss-of-function mutations in the human GDF1 gene contribute to cardiac defects ranging from tetralogy of Fallot to transposition of the great arteries and that decreased TGF- beta signaling provides a framework for understanding their pathogenesis. These findings implicate perturbations of the TGF- beta signaling pathway in the causation of a major subclass of human CHDs.