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- Integrative Response Therapy for Binge Eating Disorder.Robinson ACogn Behav Pract
- The Effect of "Single" vs "Double" Eyelids on the Perceived Attractiveness of Chinese Women.Hwang HS, Spiegel JHAesthet Surg J
- Fertility issues in cancer survivorship.Kort JD, Eisenberg ML, Millheiser LS, Westphal LMCA Cancer J Clin
- IpO: Plasmids and methods for simplified, PCR-based DNA transplant in yeast.Horecka J, Chu AM, Davis RWYeast
- PROMISE: Parallel-imaging and compressed-sensing reconstruction of multicontrast imaging using SharablE information.Gong E, Huang F, Ying K, Wu W, Wang S, Yuan CMagn Reson Med
- The functional consequences of variation in transcription factor binding.Cusanovich DA, Pavlovic B, Pritchard JK, Gilad YPLoS Genet
- Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age.Allyse M, Sayres LC, Goodspeed TA, Cho MKJ Perinatol
- Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma.Kang JH, Loomis SJ, Yaspan BL, Bailey JC, Weinreb RN, Lee RK, Lichter PR, Budenz DL, Liu Y, Realini T, Gaasterland D, Gaasterland T, Friedman DS, McCarty CA, Moroi SE, Olson L, Schuman JS, Singh K, Vollrath D, Wollstein G, Zack DJ, Brilliant M, Sit AJ, Christen WG, Fingert J, Forman JP, Buys ES, Kraft P, Zhang K, Allingham RR, Pericak-Vance MA, Richards JE, Hauser MA, Haines JL, Wiggs JL, Pasquale LREye (Lond)
- Antiphospholipid antibody-associated choroidopathy.Silva RA, Moshfeghi DMEye (Lond)
- MIR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages.Vinod M, Chennamsetty I, Colin S, Belloy L, De Paoli F, Schaider H, Graier WF, Frank S, Kratky D, Staels B, Chinetti-Gbaguidi G, Kostner GMBiochim Biophys Acta
- Arterial Spin-Labeled Perfusion Imaging in Acute Ischemic Stroke.Zaharchuk GStroke
- Burnout in pediatric residents over a 2-year period: a longitudinal study.Pantaleoni JL, Augustine EM, Sourkes BM, Bachrach LKAcad Pediatr
- Parental Limited English Proficiency and Health Outcomes for Children With Special Health Care Needs: A Systematic Review.Eneriz-Wiemer M, Sanders LM, Barr DA, Mendoza FSAcad Pediatr
- Reframing the disparities agenda: a time to rethink, a time to focus.Horn IB, Mendoza FSAcad Pediatr
- Antinociceptive Effects of Sustained-Release Buprenorphine in a Model of Incisional Pain in Rats (Rattus norvegicus).Chum HH, Jampachairsri K, McKeon GP, Yeomans DC, Pacharinsak C, Felt SAJ Am Assoc Lab Anim Sci
- Response to letter to the editor regarding "Application of principal component analysis in clinical gait research"Federolf P, Boyer K, Andriacchi TJ Biomech
- Retinal representation of the elementary visual signal.Li PH, Field GD, Greschner M, Ahn D, Gunning DE, Mathieson K, Sher A, Litke AM, Chichilnisky EJNeuron
- Site-directed mutagenesis maps interactions that enhance cognate and limit promiscuous catalysis by an alkaline phosphatase superfamily phosphodiesterase.Wiersma-Koch H, Sunden F, Herschlag DBiochemistry
- Knowledge of and attitudes toward mental illness among primary care providers in Saint Vincent and the Grenadines.Winer RA, Morris-Patterson A, Smart Y, Bijan I, Katz CLPsychiatr Q
- Modeling perceptual similarity measures in CT images of focal liver lesions.Faruque J, Rubin DL, Beaulieu CF, Napel SJ Digit Imaging
- Automatic retrieval of bone fracture knowledge using natural language processing.Do BH, Wu AS, Maley J, Biswal SJ Digit Imaging
Integrative Response Therapy for Binge Eating Disorder.
Cogn Behav Pract. 2013 Feb 1;20(1):93-105
Authors: Robinson A
Binge Eating Disorder (BED), a chronic condition characterized by eating disorder psychopathology and physical and social disability, represents a significant public health problem. Guided Self Help (GSH) treatments for BED appear promising and may be more readily disseminable to mental health care providers, accessible to patients, and cost-effective than existing, efficacious BED specialty treatments which are limited in public health utility and impact given their time and expense demands. No existing BED GSH treatment has incorporated affect regulation models of binge eating, which appears warranted given research linking negative affect and binge eating. Integrative Response Therapy (IRT), a new group-based guided self-help treatment, based on the affect regulation model of binge eating, that has shown initial promise in a pilot sample of adults meeting DSM IV criteria for BED, is described. Fifty-four% and 67% of participants were abstinent at post-treatment and three month follow-up respectively. There was a significant reduction in the number of binge days over the previous 28 days from baseline to post-treatment [14.44 (±7.16) to 3.15 (±5.70); t=7.71, p<.001; d=2.2] and from baseline to follow-up [14.44 (±7.16) to 1.50 (±2.88); t=5.64, p<.001; d=1.7]. All subscales from both the Eating Disorder Examination - Questionnaire and Emotional Eating Scale were significantly lower at post-treatment compared to baseline. 100% of IRT participants would recommend the program to a friend or family member in need. IRT's longer-term efficacy and acceptability are presently being tested in a National Institute of Mental Health funded randomized controlled trial.
PMID: 24605043 [PubMed - as supplied by publisher]
The Effect of "Single" vs "Double" Eyelids on the Perceived Attractiveness of Chinese Women.
Aesthet Surg J. 2014 Mar 6;
Authors: Hwang HS, Spiegel JH
Background:A well-defined supratarsal crease has often been considered attractive, representing a significant component in a beautiful upper eyelid. Approximately 50% of East and Southeast Asian women are born with either a minimal or absent supratarsal eyelid crease. Among people of Chinese descent, the creation of a supratarsal crease ("double" eyelid blepharoplasty) is the most common cosmetic surgical procedure, but no comparative study has assessed the height by which an upper eyelid crease is deemed most attractive and depending on cultural background.Objectives:The authors assess how attractiveness is interpreted by different cultural groups to determine whether double-eyelid blepharoplasty enhances attractiveness according to both Chinese and non-Chinese observers.Methods:Facial photographs were taken of 19 women of Chinese descent. The photographs were enhanced with computer imaging software to generate 3 additional pictures, depicting low, medium, and high upper eyelid creases on each model. Via an Internet-based survey tool, Chinese and non-Chinese observers were asked to rate the attractiveness of the faces with each potential eyelid position. (Surveys are available online at www.aestheticsurgeryjournal.com, as Appendix 1 and Appendix 2.)Results:Both Chinese and non-Chinese observers considered the medium-height upper eyelid crease most attractive (P < .00001). An absent upper eyelid crease was deemed the least attractive (P < .00001).Conclusions:These preference data for eyelid height can be used to better counsel patients on perceived attractiveness and expectations for surgical results, since these results further elucidate which facial features are universally considered attractive.
PMID: 24604790 [PubMed - as supplied by publisher]
Fertility issues in cancer survivorship.
CA Cancer J Clin. 2013 Oct 29;
Authors: Kort JD, Eisenberg ML, Millheiser LS, Westphal LM
Answer questions and earn CME/CNE Breakthroughs in cancer diagnosis and treatment have led to dramatic improvements in survival and the need to focus on survivorship issues. Chemotherapy and radiotherapy can be gonadotoxic, resulting in impaired fertility. Techniques to help cancer survivors reproduce have been improving over the past decade. Discussion of the changes to a patient's reproductive health after cancer treatment is essential to providing comprehensive quality care. The purpose of this review is to aid in pre- and posttreatment counseling, focusing on fertility preservation and other strategies that may mitigate risks to the patient's reproductive, sexual, and overall health. CA Cancer J Clin 2013. (©) 2013 American Cancer Society, Inc.
PMID: 24604743 [PubMed - as supplied by publisher]
IpO: Plasmids and methods for simplified, PCR-based DNA transplant in yeast.
Yeast. 2014 Mar 6;
Authors: Horecka J, Chu AM, Davis RW
Many yeast experiments require strains modified by recombinant DNA methods. Some experiments require precise insertion of a DNA segment into the genome without a selectable marker remaining. For these applications, we developed a new PCR-based method for marker-free DNA transplant. The current PCR-based method requires the labor-intensive construction of a PCR template plasmid with repeats of the DNA segment flanking URA3. The design of a new vector, IpO, reduces the work to cloning a single copy of the DNA segment between overlapping URA3 fragments present in the vector. Two PCRs are performed that capture the DNA segment and one or the other URA3 fragment. When the PCR products are co-transformed into yeast, recombination between the overlapping URA3 fragments restores URA3 and transposes the cloned DNA segment inside out, creating a repeat-URA3-repeat cassette. Sequences designed into the PCR primers target integration of the cassette into the genome. Subsequent selection with 5-fluoro-orotic acid yields strains that have popped out URA3 via recombination between the DNA repeats, with the result being the precise insertion of the DNA segment minus the selectable marker. An additional advantage of the IpO method is that it eliminates PCR artifacts that can plague the current method's repeat-containing templates. This article is protected by copyright. All rights reserved.
PMID: 24604451 [PubMed - as supplied by publisher]
PROMISE: Parallel-imaging and compressed-sensing reconstruction of multicontrast imaging using SharablE information.
Magn Reson Med. 2014 Feb 25;
Authors: Gong E, Huang F, Ying K, Wu W, Wang S, Yuan C
PURPOSE: A typical clinical MR examination includes multiple scans to acquire images with different contrasts for complementary diagnostic information. The multicontrast scheme requires long scanning time. The combination of partially parallel imaging and compressed sensing (CS-PPI) has been used to reconstruct accelerated scans. However, there are several unsolved problems in existing methods. The target of this work is to improve existing CS-PPI methods for multicontrast imaging, especially for two-dimensional imaging.
THEORY AND METHODS: If the same field of view is scanned in multicontrast imaging, there is significant amount of sharable information. It is proposed in this study to use manifold sharable information among multicontrast images to enhance CS-PPI in a sequential way. Coil sensitivity information and structure based adaptive regularization, which were extracted from previously reconstructed images, were applied to enhance the following reconstructions. The proposed method is called Parallel-imaging and compressed-sensing Reconstruction Of Multicontrast Imaging using SharablE information (PROMISE).
RESULTS: Using L1 -SPIRiT as a CS-PPI example, results on multicontrast brain and carotid scans demonstrated that lower error level and better detail preservation can be achieved by exploiting manifold sharable information. Besides, the privilege of PROMISE still exists while there is interscan motion.
CONCLUSION: Using the sharable information among multicontrast images can enhance CS-PPI with tolerance to motions. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
PMID: 24604305 [PubMed - as supplied by publisher]
The functional consequences of variation in transcription factor binding.
PLoS Genet. 2014 Mar;10(3):e1004226
Authors: Cusanovich DA, Pavlovic B, Pritchard JK, Gilad Y
One goal of human genetics is to understand how the information for precise and dynamic gene expression programs is encoded in the genome. The interactions of transcription factors (TFs) with DNA regulatory elements clearly play an important role in determining gene expression outputs, yet the regulatory logic underlying functional transcription factor binding is poorly understood. Many studies have focused on characterizing the genomic locations of TF binding, yet it is unclear to what extent TF binding at any specific locus has functional consequences with respect to gene expression output. To evaluate the context of functional TF binding we knocked down 59 TFs and chromatin modifiers in one HapMap lymphoblastoid cell line. We then identified genes whose expression was affected by the knockdowns. We intersected the gene expression data with transcription factor binding data (based on ChIP-seq and DNase-seq) within 10 kb of the transcription start sites of expressed genes. This combination of data allowed us to infer functional TF binding. Using this approach, we found that only a small subset of genes bound by a factor were differentially expressed following the knockdown of that factor, suggesting that most interactions between TF and chromatin do not result in measurable changes in gene expression levels of putative target genes. We found that functional TF binding is enriched in regulatory elements that harbor a large number of TF binding sites, at sites with predicted higher binding affinity, and at sites that are enriched in genomic regions annotated as "active enhancers."
PMID: 24603674 [PubMed - in process]
Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age.
J Perinatol. 2014 Mar 6;
Authors: Allyse M, Sayres LC, Goodspeed TA, Cho MK
Objective:To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake.Study Design:A national sample of 1861 US-based adults was surveyed using a validated online survey instrument. The survey was administered by a commercial survey research company. Respondents were randomized to receive a survey about prenatal testing for trisomy 13 and 18 or trisomy 21. Participants were asked to select among testing modalities, including cffDNA testing, and rank the features of testing that they considered most important to decision making.Result:There was substantive interest in the use of cffDNA testing rather than traditional screening mechanisms, with a minority of respondents reporting that they would support the use of both methods in combination. The lower rates of false-negative and false-positive test results and the ability to use the test earlier in the pregnancy were the most highly rated benefits of cffDNA testing. Participants expressed strong support for diagnostic confirmation via invasive testing after a positive result from either screening or cffDNA testing. However, almost one-third of participants reported that they would not endorse the use of either invasive or non-invasive prenatal testing.Conclusion:There appears to be support for uptake of non-invasive prenatal tests. Clinical guidelines should therefore go forward in providing guidance on how to integrate non-invasive methods into the current standard of care. However, our findings indicate that even when accuracy, which is rated by patients as the most important aspect of prenatal testing, is significantly improved over existing screening methods and testing is offered non-invasively, the number of individuals who reported that they would decline any testing remained the same. Attention should therefore be directed at ensuring that the right of informed refusal of prenatal testing is not impacted by new, non-invasive methods.Journal of Perinatology advance online publication, 6 March 2014; doi:10.1038/jp.2014.30.
PMID: 24603453 [PubMed - as supplied by publisher]
Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma.
Eye (Lond). 2014 Mar 7;
Authors: Kang JH, Loomis SJ, Yaspan BL, Bailey JC, Weinreb RN, Lee RK, Lichter PR, Budenz DL, Liu Y, Realini T, Gaasterland D, Gaasterland T, Friedman DS, McCarty CA, Moroi SE, Olson L, Schuman JS, Singh K, Vollrath D, Wollstein G, Zack DJ, Brilliant M, Sit AJ, Christen WG, Fingert J, Forman JP, Buys ES, Kraft P, Zhang K, Allingham RR, Pericak-Vance MA, Richards JE, Hauser MA, Haines JL, Wiggs JL, Pasquale LR
AimsVascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG.MethodsWe used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG.ResultsThe vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only.DiscussionAlthough the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.Eye advance online publication, 7 March 2014; doi:10.1038/eye.2014.42.
PMID: 24603425 [PubMed - as supplied by publisher]
Antiphospholipid antibody-associated choroidopathy.
Eye (Lond). 2014 Mar 7;
Authors: Silva RA, Moshfeghi DM
PMID: 24603416 [PubMed - as supplied by publisher]
MIR-206 controls LXRα expression and promotes LXR-mediated cholesterol efflux in macrophages.
Biochim Biophys Acta. 2014 Mar 3;
Authors: Vinod M, Chennamsetty I, Colin S, Belloy L, De Paoli F, Schaider H, Graier WF, Frank S, Kratky D, Staels B, Chinetti-Gbaguidi G, Kostner GM
Liver X receptors (LXRα and LXRβ) are key transcription factors in cholesterol metabolism that regulate cholesterol biosynthesis/efflux and bile acid metabolism/excretion in the liver and numerous organs. In macrophages, LXR signaling modulates cholesterol handling and the inflammatory response, pathways involved in atherosclerosis. Since regulatory pathways of LXR transcription control are well understood, in the present study we aimed at identifying post-transcriptional regulators of LXR activity. MicroRNAs (miRs) are such post-transcriptional regulators of genes that in the canonical pathway mediate mRNA inactivation. In silico analysis identified miR-206 as a putative regulator of LXRα but not LXRβ. Indeed, as recently shown, we found that miR-206 represses LXRα activity and expression of LXRα and its target genes in hepatic cells. Interestingly, miR-206 regulates LXRα differently in macrophages. Stably overexpressing miR-206 in THP-1 human macrophages revealed an up-regulation and miR-206 knockdown led to a down-regulation of LXRα and its target genes. In support of these results, bone marrow-derived macrophages (BMDM) from miR-206 KO mice also exhibited lower expression of LXRα target genes. The physiological relevance of these findings was proven by gain-and loss-of-function of miR-206; overexpression of miR-206 enhanced cholesterol efflux in human macrophages and knocking out miR-206 decreased cholesterol efflux from MPMs. Moreover, we show that miR-206 expression in macrophages is repressed by LXRα activation, while oxidized LDL and inflammatory stimuli profoundly induced miR-206 expression. We therefore propose a feed-back loop between miR-206 and LXRα that might be part of an LXR auto-regulatory mechanism to fine tune LXR activity.
PMID: 24603323 [PubMed - as supplied by publisher]
Arterial Spin-Labeled Perfusion Imaging in Acute Ischemic Stroke.
Stroke. 2014 Mar 6;
Authors: Zaharchuk G
PMID: 24603069 [PubMed - as supplied by publisher]
Burnout in pediatric residents over a 2-year period: a longitudinal study.
Acad Pediatr. 2014 Mar-Apr;14(2):167-72
Authors: Pantaleoni JL, Augustine EM, Sourkes BM, Bachrach LK
OBJECTIVE: Burnout is a work-related syndrome characterized by emotional exhaustion (EE), depersonalization (DP), and lack of personal accomplishment (PA). We hypothesized that the transition into an environment of high physical, intellectual, and emotional demands of the medical profession would lead to an increase in the prevalence of burnout in pediatric residents, which would remain high throughout residency.
METHODS: The Maslach Burnout Inventory (MBI) was administered to pediatric residents at Lucile Packard Children's Hospital 6 times between February 2010 and February 2012. These times corresponded to the start of residency, mid-intern year, end-intern year, mid-junior year, end-junior year, and mid-senior year.
RESULTS: Mean values of burnout components changed significantly between the start of residency and mid-intern year. EE increased from 15.8 to 24.5 (P < .001), DP increased from 4.5 to 9.2 (P < .001), and PA decreased from 40.2 to 38.3 (P = .04). Similarly, the prevalence of burnout increased from 17% to 46% (P = .012), or 2% to 24% (P = .002) using more restrictive criteria, between the start of residency and mid-intern year. Significant changes in mean scores or prevalence of burnout were not found between any other consecutive times throughout residency.
CONCLUSIONS: This longitudinal study documented a significant increase in the components of burnout among pediatric residents between the start of residency and mid-intern year, which persisted through the PGY2 and PGY3 years. Further studies are warranted to identify correlates of resident burnout and to develop preventative strategies to reduce its occurrence.
PMID: 24602580 [PubMed - in process]
Parental Limited English Proficiency and Health Outcomes for Children With Special Health Care Needs: A Systematic Review.
Acad Pediatr. 2014 March - April;14(2):128-136
Authors: Eneriz-Wiemer M, Sanders LM, Barr DA, Mendoza FS
BACKGROUND: One in 10 US adults of childbearing age has limited English proficiency (LEP). Parental LEP is associated with worse health outcomes among healthy children. The relationship of parental LEP to health outcomes for children with special health care needs (CSHCN) has not been systematically reviewed.
OBJECTIVE: To conduct a systematic review of peer-reviewed literature examining relationships between parental LEP and health outcomes for CSHCN.
DATA SOURCES: PubMed, Scopus, Cochrane Library, Social Science Abstracts, bibliographies of included studies. Key search term categories: language, child, special health care needs, and health outcomes.
ELIGIBILITY CRITERIA: US studies published between 1964 and 2012 were included if: 1) subjects were CSHCN; 2) studies included some measure of parental LEP; 3) at least 1 outcome measure of child health status, access, utilization, costs, or quality; and 4) primary or secondary data analysis.
METHODS: Three trained reviewers independently screened studies and extracted data. Two separate reviewers appraised studies for methodological rigor and quality.
RESULTS: From 2765 titles and abstracts, 31 studies met eligibility criteria. Five studies assessed child health status, 12 assessed access, 8 assessed utilization, 2 assessed costs, and 14 assessed quality. Nearly all (29 of 31) studies used only parent- or child-reported outcome measures, rather than objective measures. LEP parents were substantially more likely than English-proficient parents to report that their CSHCN were uninsured and had no usual source of care or medical home. LEP parents were also less likely to report family-centered care and satisfaction with care. Disparities persisted for children with LEP parents after adjustment for ethnicity and socioeconomic status.
CONCLUSIONS AND IMPLICATIONS: Parental LEP is independently associated with worse health care access and quality for CSHCN. Health care providers should recognize LEP as an independent risk factor for poor health outcomes among CSHCN. Emerging models of chronic disease care should integrate and evaluate interventions that target access and quality disparities for LEP families.
PMID: 24602575 [PubMed - as supplied by publisher]
Reframing the disparities agenda: a time to rethink, a time to focus.
Acad Pediatr. 2014 Mar-Apr;14(2):115-6
Authors: Horn IB, Mendoza FS
PMID: 24602572 [PubMed - in process]
Antinociceptive Effects of Sustained-Release Buprenorphine in a Model of Incisional Pain in Rats (Rattus norvegicus).
J Am Assoc Lab Anim Sci. 2014;53(2):193-7
Authors: Chum HH, Jampachairsri K, McKeon GP, Yeomans DC, Pacharinsak C, Felt SA
Effective management of postoperative pain is an essential component of the care and welfare of laboratory animals. A sustained-release formulation of buprenorphine (Bup-SR) has recently been introduced to the veterinary market and has been reported to provide analgesia for as long as 72 h. Using evoked mechanical and thermal hypersensitivity tests, we here evaluated the antinociceptive effects of Bup-SR in a model of incisional pain in rats. Paw withdrawal responses were obtained before and 1 through 4 d after surgery. Rats are assigned to receive Bup-SR (0.3, 1.2, or 4.5 mg/kg SC once) or buprenorphine HCl (Bup HCl, 0.05 mg/kg SC twice daily for 3 d). Responses to mechanical and thermal stimuli in the 1.2 and 4.5 Bup-SR groups did not differ from those of rats in the Bup HCl group. Thermal latency on day 3 in rats that received 0.3 mg/kg Bup-SR was significantly different from baseline, indicating that this dose effectively decreased thermal hypersensitivity for at least 48 h. Marked sedation occurred in rats in the 4.5 Bup-SR group. Our findings indicate that Bup-SR at 0.3 or 1.2 mg/kg SC is effective in minimizing hypersensitivity with minimal sedation for at least 48 h (thermal hypersensitivity) and 72 h, respectively, in the incisional pain model in rats.
PMID: 24602547 [PubMed - in process]
Response to letter to the editor regarding "Application of principal component analysis in clinical gait research"
J Biomech. 2014 Feb 21;
Authors: Federolf P, Boyer K, Andriacchi T
PMID: 24602290 [PubMed - as supplied by publisher]
Retinal representation of the elementary visual signal.
Neuron. 2014 Jan 8;81(1):130-9
Authors: Li PH, Field GD, Greschner M, Ahn D, Gunning DE, Mathieson K, Sher A, Litke AM, Chichilnisky EJ
The propagation of visual signals from individual cone photoreceptors through parallel neural circuits was examined in the primate retina. Targeted stimulation of individual cones was combined with simultaneous recording from multiple retinal ganglion cells of identified types. The visual signal initiated by an individual cone produced strong responses with different kinetics in three of the four numerically dominant ganglion cell types. The magnitude and kinetics of light responses in each ganglion cell varied nonlinearly with stimulus strength but in a manner that was independent of the cone of origin after accounting for the overall input strength of each cone. Based on this property of independence, the receptive field profile of an individual ganglion cell could be well estimated from responses to stimulation of each cone individually. Together, these findings provide a quantitative account of how elementary visual inputs form the ganglion cell receptive field.
PMID: 24411737 [PubMed - indexed for MEDLINE]
Site-directed mutagenesis maps interactions that enhance cognate and limit promiscuous catalysis by an alkaline phosphatase superfamily phosphodiesterase.
Biochemistry. 2013 Dec 23;52(51):9167-76
Authors: Wiersma-Koch H, Sunden F, Herschlag D
Catalytic promiscuity, an evolutionary concept, also provides a powerful tool for gaining mechanistic insights into enzymatic reactions. Members of the alkaline phosphatase (AP) superfamily are highly amenable to such investigation, with several members having been shown to exhibit promiscuous activity for the cognate reactions of other superfamily members. Previous work has shown that nucleotide pyrophosphatase/phosphodiesterase (NPP) exhibits a >10⁶-fold preference for the hydrolysis of phosphate diesters over phosphate monoesters, and that the reaction specificity is reduced 10³-fold when the size of the substituent on the transferred phosphoryl group of phosphate diester substrates is reduced to a methyl group. Here we show additional specificity contributions from the binding pocket for this substituent (herein termed the R' substituent) that account for an additional ~250-fold differential specificity with the minimal methyl substituent. Removal of four hydrophobic side chains suggested on the basis of structural inspection to interact favorably with R' substituents decreases phosphate diester reactivity 10⁴-fold with an optimal diester substrate (R' = 5'-deoxythymidine) and 50-fold with a minimal diester substrate (R' = CH₃). These mutations also enhance the enzyme's promiscuous phosphate monoesterase activity by nearly an order of magnitude, an effect that is traced by mutation to the reduction of unfavorable interactions with the two residues closest to the nonbridging phosphoryl oxygen atoms. The quadruple R' pocket mutant exhibits the same activity toward phosphate diester and phosphate monoester substrates that have identical leaving groups, with substantial rate enhancements of ~10¹¹-fold. This observation suggests that the Zn²⁺ bimetallo core of AP superfamily enzymes, which is equipotent in phosphate monoester and diester catalysis, has the potential to become specialized for the hydrolysis of each class of phosphate esters via addition of side chains that interact with the substrate atoms and substituents that project away from the Zn²⁺ bimetallo core.
PMID: 24261692 [PubMed - indexed for MEDLINE]
Knowledge of and attitudes toward mental illness among primary care providers in Saint Vincent and the Grenadines.
Psychiatr Q. 2013 Sep;84(3):395-406
Authors: Winer RA, Morris-Patterson A, Smart Y, Bijan I, Katz CL
Saint Vincent and the Grenadines (SVG) is an Eastern Caribbean country with limited inpatient and outpatient resources to meet the country's mental health needs. In preparation for integrating mental health care into the primary care setting, we assessed knowledge of and attitudes toward mental illness among primary care providers in SVG. From October 24-November 11, 2011, we visited a convenience sample of District Health Centers in SVG. We gave a multiple-choice-answer, self-administered questionnaire to primary care providers and then administered a structured interview. Survey responses were analyzed for frequencies and interview transcripts qualitatively analyzed for major themes. We completed 53 surveys and interviews representing all nine SVG Health Districts. Results demonstrated a provider population with basic, but inadequate, knowledge of mental illness diagnosis and treatment. Results also revealed a curious and interested group of providers who felt mental illness should be a health priority and were willing and eager to receive further mental health training. Providers suggested strengthening resources in existing district clinics, providing additional staff training sessions, establishing positions with a dual health and mental health role, instituting annual mental health screening examinations, and creating weekly mental health clinics. Integrating mental health care into primary care necessitates involvement of primary care staff during the planning stages, and this study initiates an intensive effort to do so in SVG. Results have led to the development of a "mental health check-up" tool, which we hope will improve access to mental health care in this community.
PMID: 23378041 [PubMed - indexed for MEDLINE]
Modeling perceptual similarity measures in CT images of focal liver lesions.
J Digit Imaging. 2013 Aug;26(4):714-20
Authors: Faruque J, Rubin DL, Beaulieu CF, Napel S
MOTIVATION: A gold standard for perceptual similarity in medical images is vital to content-based image retrieval, but inter-reader variability complicates development. Our objective was to develop a statistical model that predicts the number of readers (N) necessary to achieve acceptable levels of variability.
MATERIALS AND METHODS: We collected 3 radiologists' ratings of the perceptual similarity of 171 pairs of CT images of focal liver lesions rated on a 9-point scale. We modeled the readers' scores as bimodal distributions in additive Gaussian noise and estimated the distribution parameters from the scores using an expectation maximization algorithm. We (a) sampled 171 similarity scores to simulate a ground truth and (b) simulated readers by adding noise, with standard deviation between 0 and 5 for each reader. We computed the mean values of 2-50 readers' scores and calculated the agreement (AGT) between these means and the simulated ground truth, and the inter-reader agreement (IRA), using Cohen's Kappa metric.
RESULTS: IRA for the empirical data ranged from =0.41 to 0.66. For between 1.5 and 2.5, IRA between three simulated readers was comparable to agreement in the empirical data. For these values , AGT ranged from =0.81 to 0.91. As expected, AGT increased with N, ranging from =0.83 to 0.92 for N = 2 to 50, respectively, with =2.
CONCLUSION: Our simulations demonstrated that for moderate to good IRA, excellent AGT could nonetheless be obtained. This model may be used to predict the required N to accurately evaluate similarity in arbitrary size datasets.
PMID: 23254627 [PubMed - indexed for MEDLINE]
Automatic retrieval of bone fracture knowledge using natural language processing.
J Digit Imaging. 2013 Aug;26(4):709-13
Authors: Do BH, Wu AS, Maley J, Biswal S
Natural language processing (NLP) techniques to extract data from unstructured text into formal computer representations are valuable for creating robust, scalable methods to mine data in medical documents and radiology reports. As voice recognition (VR) becomes more prevalent in radiology practice, there is opportunity for implementing NLP in real time for decision-support applications such as context-aware information retrieval. For example, as the radiologist dictates a report, an NLP algorithm can extract concepts from the text and retrieve relevant classification or diagnosis criteria or calculate disease probability. NLP can work in parallel with VR to potentially facilitate evidence-based reporting (for example, automatically retrieving the Bosniak classification when the radiologist describes a kidney cyst). For these reasons, we developed and validated an NLP system which extracts fracture and anatomy concepts from unstructured text and retrieves relevant bone fracture knowledge. We implement our NLP in an HTML5 web application to demonstrate a proof-of-concept feedback NLP system which retrieves bone fracture knowledge in real time.
PMID: 23053906 [PubMed - indexed for MEDLINE]