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1.  Understanding the effect of insurance expansion on utilization of inpatient surgery 
JAMA surgery  2014;149(8):829-836.
Importance
While the enthusiasm for the Affordable Care Act (ACA) revolves around its impact on access to preventive and primary care services, the effect of this reform on surgical care remains undefined.
Objective
Using Massachusetts (MA) healthcare reform as a natural experiment, we estimate the differential impact of insurance expansion on the utilization of discretionary versus non-discretionary inpatient surgery.
Design
We used the State Inpatient Databases from MA and two control states to identify nonelderly patients (19–64 years) who underwent discretionary (DS) versus non-discretionary surgery (NDS) during the years 2003–2010. We defined DS as elective, preference-sensitive procedures (e.g., joint replacement, back surgery), and NDS as imperative and potentially lifesaving procedures (e.g., cancer surgery, hip fracture repair). Using July 2007 as the transition point between pre and post-reform periods, we performed a difference-in-differences (DID) analysis to estimate the effect of insurance expansion on rates of DS vs NDS among the entire study population, and for subgroups defined by race, income and insurance status. We then extrapolated our results from MA to the entire US population.
Main Outcome(s) and Measure(s)
Rate of DS and NDS performed before and after the healthcare reform in Massachusetts.
Results
We identified a total of 836,311 surgeries during the study period. In contrast to NDS, post-reform rates of DS increased more in MA than in control states. Based on our DID analysis, insurance expansion was associated with a 9.3% increase in the use of DS in MA (p=0.021). Conversely, the rate of NDS decreased by 4.5% (p=0.009). We found similar effects for DS in all subgroups, with the greatest increase observed for non-whites (19.9%, p<0.001). Based on the findings in MA, we estimated that full implementation of national insurance expansion would yield an additional 465,934 discretionary surgeries by 2017.
Conclusions and Relevance
Insurance expansion in Massachusetts was associated with increased rates of discretionary surgery, and a concurrent decrease in utilization of nondiscretionary surgery. If similar changes are seen nationally, the value of insurance expansion for surgical care may depend on the relative balance between increased expenditures and potential health benefits of greater access to elective inpatient procedures.
doi:10.1001/jamasurg.2014.857
PMCID: PMC4209916  PMID: 24988945
2.  Building National Capacity for Research Mentor Training: An Evidence-Based Approach to Training the Trainers 
CBE Life Sciences Education  2015;14(2):ar24.
This article describes the development, implementation, evaluation, and impact of a train-the-trainer workshop designed to promote widespread dissemination of an evidence-based research mentor training curriculum.
Research mentor training (RMT), based on the published Entering Mentoring curricula series, has been shown to improve the knowledge and skills of research mentors across career stages, as self-reported by both the mentors engaged in training and their mentees. To promote widespread dissemination and empower others to implement this evidence-based training at their home institutions, we developed an extensive, interactive, multifaceted train-the-trainer workshop. The specific goals of these workshops are to 1) increase facilitator knowledge of an RMT curriculum, 2) increase facilitator confidence in implementing the curriculum, 3) provide a safe environment to practice facilitation of curricular activities, and 4) review implementation strategies and evaluation tools. Data indicate that our approach results in high satisfaction and significant confidence gains among attendees. Of the 195 diverse attendees trained in our workshops since Fall 2010, 44% report implementation at 39 different institutions, collectively training more than 500 mentors. Further, mentors who participated in the RMT sessions led by our trained facilitators report high facilitator effectiveness in guiding discussion. Implications and challenges to building the national capacity needed for improved research mentoring relationships are discussed.
doi:10.1187/cbe.14-10-0184
PMCID: PMC4477740  PMID: 26033872
3.  A Portal into Biology Education: An Annotated List of Commonly Encountered Terms 
CBE Life Sciences Education  2015;14(2):fe2.
Exploring a new discipline can be daunting in any field, and biology education is no exception. The authors provide a resource for those who are new to explorations of the biology education and biology education research worlds, including key terminology, brief definitions, and links to literature for further explorations.
doi:10.1187/cbe.15-03-0065
PMCID: PMC4477742  PMID: 26033868
4.  Personality, Cognitive Style, Motivation, and Aptitude Predict Systematic Trends in Analytic Forecasting Behavior 
The decision sciences are increasingly challenged to advance methods for modeling analysts, accounting for both analytic strengths and weaknesses, to improve inferences taken from increasingly large and complex sources of data. We examine whether psychometric measures—personality, cognitive style, motivated cognition—predict analytic performance and whether psychometric measures are competitive with aptitude measures (i.e., SAT scores) as analyst sample selection criteria. A heterogeneous, national sample of 927 participants completed an extensive battery of psychometric measures and aptitude tests and was asked 129 geopolitical forecasting questions over the course of 1 year. Factor analysis reveals four dimensions among psychometric measures; dimensions characterized by differently motivated “top-down” cognitive styles predicted distinctive patterns in aptitude and forecasting behavior. These dimensions were not better predictors of forecasting accuracy than aptitude measures. However, multiple regression and mediation analysis reveals that these dimensions influenced forecasting accuracy primarily through bias in forecasting confidence. We also found that these facets were competitive with aptitude tests as forecast sampling criteria designed to mitigate biases in forecasting confidence while maximizing accuracy. These findings inform the understanding of individual difference dimensions at the intersection of analytic aptitude and demonstrate that they wield predictive power in applied, analytic domains.
doi:10.1177/1555343414554702
PMCID: PMC4361467  PMID: 25983670
individual differences; analysts; forecasting; personality; cognitive style
5.  OnabotulinumtoxinA for Hemicrania Continua: open label experience in 9 patients 
Background
Hemicrania continua is a strictly unilateral, continuous headache, typically mild to moderate in severity, with severe exacerbations commonly accompanied by cranial autonomic features and migrainous symptoms. It is exquisitely responsive to Indomethacin. However, some patients cannot tolerate treatment, often due to gastrointestinal side effects. Therapeutic alternatives are limited and controlled evidence lacking.
Methods
We present our experience of nine patients treated with OnabotulinumtoxinA for hemicrania continua. All patients were injected using the PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) protocol for migraine.
Results
Five of nine patients demonstrated a 50% or more reduction in moderate to severe headache days with OnabotulinumtoxinA with a median reduction in moderate to severe headache days of 80%. Patient estimate of response was 80% or more in five subjects. The median and mean duration of response in the five responders was 11 and 12 weeks (range 6–20 weeks). Improvements were also seen in headache-associated disability
Conclusions
OnabotulinumtoxinA adds a potential option to the limited therapeutic alternatives available in hemicrania continua.
doi:10.1186/s10194-015-0502-z
PMCID: PMC4385246  PMID: 25902798
Botulinum toxin-A; Hemicrania continua; Treatment; Indomethacin
6.  Anticipating the impact of insurance expansion on inpatient urological surgery 
Urology practice  2014;1(3):134-140.
PURPOSE
The Affordable Care Act (ACA) is expected to provide coverage for nearly twenty-five million previously uninsured individuals. Because the potential impact of the ACA for urological care remains unknown, we estimated the impact of insurance expansion on the utilization of inpatient urological surgeries using Massachusetts (MA) healthcare reform as a natural experiment.
METHODS
We identified nonelderly patients who underwent inpatient urological surgery from 2003 through 2010 using inpatient databases from MA and two control states. Using July 2007 as the transition point between pre- and post-reform periods, we performed a difference-indifferences (DID) analysis to estimate the effect of insurance expansion on overall and procedure-specific rates of inpatient urological surgery. We also performed subgroup analyses according to race, income and insurance status.
RESULTS
We identified 1.4 million surgeries performed during the study interval. We observed no change in the overall rate of inpatient urological surgery for the MA population as a whole, but an increase in the rate of inpatient urological surgery for non-white and low income patients. Our DID analysis confirmed these results (all 1.0%, p=0.668; non-whites 9.9%, p=0.006; low income 6.6%, p=0.041). At a procedure level, insurance expansion caused increased rates of inpatient BPH procedures, but had no effect on rates of prostatectomy, cystectomy, nephrectomy, pyeloplasty or PCNL.
CONCLUSIONS
Insurance expansion in Massachusetts increased the overall rate of inpatient urological surgery only for non-whites and low income patients. These data inform key stakeholders about the potential impact of national insurance expansion for a large segment of urological care.
doi:10.1016/j.urpr.2014.05.002
PMCID: PMC4258712  PMID: 25506058
7.  Neuronal Activity Promotes Oligodendrogenesis and Adaptive Myelination in the Mammalian Brain 
Science (New York, N.Y.)  2014;344(6183):1252304.
Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity–regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.
doi:10.1126/science.1252304
PMCID: PMC4096908  PMID: 24727982
8.  Enteric neural crest-derived cells promote their migration by modifying their microenvironment through tenascin-C production 
Developmental biology  2013;382(2):446-456.
The enteric nervous system (ENS) is derived from vagal and sacral neural crest cells that migrate, proliferate, and differentiate into enteric neurons and glia within the gut wall. The mechanisms regulating enteric neural crest-derived cell (ENCC) migration are poorly characterized despite the importance of this process in gut formation and function. Characterization of genes involved in ENCC migration is essential to understanding ENS development and could provide targets for treatment of human ENS disorders. We identified the extracellular matrix glycoprotein tenascin-C (TNC) as an important regulator of ENCC development. We find TNC dynamically expressed during avian gut development. It is absent from the cecal region just prior to ENCC arrival, but becomes strongly expressed around ENCCs as they enter the ceca and hindgut. In aganglionic hindguts, TNC expression is strong throughout the outer mesenchyme, but is absent from the submucosal region, supporting the presence of both ENCC-dependent and independent expression within the gut wall. Using rat-chick coelomic grafts, neural tube cultures, and gut explants, we show that ENCCs produce TNC and that this ECM protein promotes their migration. Interestingly, only vagal neural crest-derived ENCCs express TNC, whereas sacral neural crest-derived cells do not. These results demonstrate that vagal crest-derived ENCCs actively modify their microenvironment through TNC expression and thereby help to regulate their own migration.
doi:10.1016/j.ydbio.2013.08.006
PMCID: PMC3800188  PMID: 23958436
Enteric nervous system; extracellular matrix; neural crest cells; tenascin-C; Hirschsprung disease
9.  Invited Commentary: Broadening the Evidence for Adolescent Sexual and Reproductive Health and Education in the United States 
Journal of Youth and Adolescence  2014;43(10):1595-1610.
Scientific research has made major contributions to adolescent health by providing insights into factors that influence it and by defining ways to improve it. However, US adolescent sexual and reproductive health policies—particularly sexuality health education policies and programs—have not benefited from the full scope of scientific understanding. From 1998 to 2009, federal funding for sexuality education focused almost exclusively on ineffective and scientifically inaccurate abstinence-only-until-marriage (AOUM) programs. Since 2010, the largest source of federal funding for sexual health education has been the “tier 1” funding of the Office of Adolescent Health’s Teen Pregnancy Prevention Initiative. To be eligible for such funds, public and private entities must choose from a list of 35 programs that have been designated as “evidence-based” interventions (EBIs), determined based on their effectiveness at preventing teen pregnancies, reducing sexually transmitted infections, or reducing rates of sexual risk behaviors (i.e., sexual activity, contraceptive use, or number of partners). Although the transition from primarily AOUM to EBI is important progress, this definition of evidence is narrow and ignores factors known to play key roles in adolescent sexual and reproductive health. Important bodies of evidence are not treated as part of the essential evidence base, including research on lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) youth; gender; and economic inequalities and health. These bodies of evidence underscore the need for sexual health education to approach adolescent sexuality holistically, to be inclusive of all youth, and to address and mitigate the impact of structural inequities. We provide recommendations to improve US sexual health education and to strengthen the translation of science into programs and policy.
doi:10.1007/s10964-014-0178-8
PMCID: PMC4162986  PMID: 25200033
10.  The TRIM-NHL Protein LIN-41 Controls the Onset of Developmental Plasticity in Caenorhabditis elegans 
PLoS Genetics  2014;10(8):e1004533.
The mechanisms controlling cell fate determination and reprogramming are fundamental for development. A profound reprogramming, allowing the production of pluripotent cells in early embryos, takes place during the oocyte-to-embryo transition. To understand how the oocyte reprogramming potential is controlled, we sought Caenorhabditis elegans mutants in which embryonic transcription is initiated precociously in germ cells. This screen identified LIN-41, a TRIM-NHL protein and a component of the somatic heterochronic pathway, as a temporal regulator of pluripotency in the germline. We found that LIN-41 is expressed in the cytoplasm of developing oocytes, which, in lin-41 mutants, acquire pluripotent characteristics of embryonic cells and form teratomas. To understand LIN-41 function in the germline, we conducted structure-function studies. In contrast to other TRIM-NHL proteins, we found that LIN-41 is unlikely to function as an E3 ubiquitin ligase. Similar to other TRIM-NHL proteins, the somatic function of LIN-41 is thought to involve mRNA regulation. Surprisingly, we found that mutations predicted to disrupt the association of LIN-41 with mRNA, which otherwise compromise LIN-41 function in the heterochronic pathway in the soma, have only minor effects in the germline. Similarly, LIN-41-mediated repression of a key somatic mRNA target is dispensable for the germline function. Thus, LIN-41 appears to function in the germline and the soma via different molecular mechanisms. These studies provide the first insight into the mechanism inhibiting the onset of embryonic differentiation in developing oocytes, which is required to ensure a successful transition between generations.
Author Summary
Reprogramming into a naïve, pluripotent state during the oocyte-to-embryo transition is directed by the oocyte cytoplasm. To understand how this reprogramming is controlled, we searched for C. elegans mutants in which the activation of embryonic genome, a landmark event demarcating the switch from a germline- to embryo-specific transcription, is initiated precociously in germ cells. This screen identified a novel function for LIN-41, a member of the TRIM-NHL protein family, in preventing a premature onset of embryonic-like differentiation and teratoma formation in developing oocytes, thus ensuring a successful passage between generations. This is the first example of such a regulator in cells that are poised for embryonic development. Interestingly, the majority of molecular “roadblocks” to reprograming that have been identified so far are epigenetic regulators. However, we propose that, at least in germ cells, LIN-41-like regulators may fulfill an analogous role in the cytoplasm, which has possible implications for the generation of human pluripotent stem cells.
doi:10.1371/journal.pgen.1004533
PMCID: PMC4148191  PMID: 25167051
11.  Trigeminal Autonomic Cephalalgias: Beyond the Conventional Treatments 
The trigeminal autonomic cephalalgias include cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua. While the majority responds to conventional pharmacological treatments, a small but significant proportion of patients are intractable to these treatments. In these cases, alternative choices for these patients include oral and injectable drugs, lesional or resectional surgery, and neurostimulation. The evidence base for conventional treatments is limited, and the evidence for those used beyond convention is more so. At present, the most evidence exists for nerve blocks, deep brain stimulation, occipital nerve stimulation, sphenopalatine ganglion stimulation in chronic cluster headache, and microvascular decompression of the trigeminal nerve in short-lasting unilateral neuralgiform headache attacks.
doi:10.1007/s11916-014-0438-z
PMCID: PMC4119587  PMID: 24974071
Trigeminal autonomic cephalalgias; Neurostimulation; Nerve blocks; Sphenopalatine ganglion stimulation; Occipital nerve stimulation; Deep brain stimulation
12.  COMBS: A Biosurveillance Ecosystem (BSVE) Prototype 
doi:10.5210/ojphi.v6i1.5060
PMCID: PMC4050829
biosurveillance; public health; identify threats; analyst workbench
13.  Hypnosis: There’s an App for that. A systematic review of hypnosis apps 
The study systematically reviews the hypnosis apps available via iTunes that were compatible with iPhone or iPad. Of 1455 apps identified on iTunes, 407 met inclusion criteria and were further reviewed. Most common hypnosis app targets were: weight loss (23%), boosting self-esteem (20%), and relaxation/stress reduction (19%). 83% of apps delivered hypnosis via audio track, and 37% allowed tailoring. Less than 14% of apps reported disclaimers. None of the apps reported having been tested for efficacy, and none reported being evidence-based. Although apps have the potential to enhance hypnosis delivery, it seems as though technology has raced ahead of the supporting science. Recommendations from clinical researchers and policy makers are needed to inform responsible hypnosis app development and use.
doi:10.1080/00207144.2013.810482
PMCID: PMC3804912  PMID: 23957263
14.  Human ZMPSTE24 disease mutations: residual proteolytic activity correlates with disease severity 
Human Molecular Genetics  2012;21(18):4084-4093.
The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE24 cleavage site, underlies the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). Likewise, mutations in the ZMPSTE24 gene that result in decreased enzyme function cause a spectrum of diseases that share certain features of premature aging. Twenty human ZMPSTE24 alleles have been identified that are associated with three disease categories of increasing severity: mandibuloacral dysplasia type B (MAD-B), severe progeria (atypical ‘HGPS’) and restrictive dermopathy (RD). To determine whether a correlation exists between decreasing ZMPSTE24 protease activity and increasing disease severity, we expressed mutant alleles of ZMPSTE24 in yeast and optimized in vivo yeast mating assays to directly compare the activity of alleles associated with each disease category. We also measured the activity of yeast crude membranes containing the ZMPSTE24 mutant proteins in vitro. We determined that, in general, the residual activity of ZMPSTE24 patient alleles correlates with disease severity. Complete loss-of-function alleles are associated with RD, whereas retention of partial, measureable activity results in MAD-B or severe progeria. Importantly, our assays can discriminate small differences in activity among the mutants, confirming that the methods presented here will be useful for characterizing any new ZMPSTE24 mutations that are discovered.
doi:10.1093/hmg/dds233
PMCID: PMC3428156  PMID: 22718200
15.  The red ear syndrome 
Red Ear Syndrome (RES) is a very rare disorder, with approximately 100 published cases in the medical literature. Red ear (RE) episodes are characterised by unilateral or bilateral attacks of paroxysmal burning sensations and reddening of the external ear. The duration of these episodes ranges from a few seconds to several hours. The attacks occur with a frequency ranging from several a day to a few per year. Episodes can occur spontaneously or be triggered, most frequently by rubbing or touching the ear, heat or cold, chewing, brushing of the hair, neck movements or exertion. Early-onset idiopathic RES seems to be associated with migraine, whereas late-onset idiopathic forms have been reported in association with trigeminal autonomic cephalalgias (TACs). Secondary forms of RES occur with upper cervical spine disorders or temporo-mandibular joint dysfunction. RES is regarded refractory to medical treatments, although some migraine preventative treatments have shown moderate benefit mainly in patients with migraine-related attacks. The pathophysiology of RES is still unclear but several hypotheses involving peripheral or central nervous system mechanisms have been proposed.
doi:10.1186/1129-2377-14-83
PMCID: PMC3850925  PMID: 24093332
Red ear syndrome; Migraine; Trigemino-autonomic reflex; Trigeminal autonomic cephalalgias; Parasympathetic system; Erythromelalgia
16.  Genetic and epigenetic alterations of steroidogenic factor-1 in ovarian tumors 
International Journal of Oncology  2012;42(2):627-634.
Steroidogenic factor-1 (SF-1), the product of the NR5A1 gene, is an essential transcription factor that is known to regulate steroidogenesis in ovarian epithelia, including the synthesis of progesterone, a suppressor of ovarian cancer. Expression of the SF-1 protein, a potential ovarian tumor suppressor, has been demonstrated in normal OSE cells, but is lost in most ovarian tumors and ovarian tumor cell lines. We examined loss of heterozygosity (LOH) and promoter methylation as potential mechanisms that may explain the loss of SF-1 protein in ovarian tumor tissues. Genotyping of three NR5A1 SNPs in matched tumor/normal tissues identified LOH in 16/36 (44%) of the ovarian tumors successfully analyzed, and somatic mutations (gain of allele) in 10% of the tumors. Furthermore, a methylation-sensitive restriction enzyme method was used to demonstrate statistically significant (p<0.0001) increase in the frequency of NR5A1 gene methylation in ovarian tumors (36/46; 78%) versus normal ovaries (1/11; 9%). These data suggest that the SF-1 encoding gene exhibits frequent genetic (LOH/base substitution) and epigenetic (methylation) somatic alterations in ovarian tumors. These data also present novel molecular mechanisms that may explain the loss of SF-1 protein in ovarian tumors, and its potential role in ovarian carcinogenesis.
doi:10.3892/ijo.2012.1758
PMCID: PMC3583749  PMID: 23291911
somatic; mutation; ovarian; carcinogenesis; steroidogenesis
17.  USING A BLOCKED-TRIALS PROCEDURE TO TEACH IDENTITY MATCHING TO A CHILD WITH AUTISM 
Children with autism may struggle in developing conditional discrimination repertoires. Saunders and Spradlin (1989, 1990, 1993) arranged “blocked” teaching trials in which they presented the same sample stimulus repeatedly across trials (in lieu of randomly alternating targets across trials) and then faded the number of trials in each block. We replicated the effects of this blocked-trials procedure in teaching identity matching to a child with autism and evaluated the necessity of fading. Arranging blocked trials facilitated the acquisition of identity matching, but fading the block size was not necessary to maintain discriminated performance.
doi:10.1901/jaba.2012.45-619
PMCID: PMC3469304  PMID: 23060677
autism; blocked trials; children; conditional discrimination; identity matching
18.  Synthesis of Unsymmetrical 3,4-Diaryl-3-pyrrolin-2-ones Utilizing Pyrrole Weinreb Amides 
The Journal of organic chemistry  2011;76(20):8203-8214.
A regiocontrolled synthesis of unsymmetrical 3,4-diaryl-3-pyrrolin-2-ones has been achieved in three steps from 1,2-diaryl-1-nitroethenes with pyrrole-2-carboxamides (pyrrole Weinreb amides) serving as the key linchpin intermediates. Two different methods for the preparation of the requisite nitroalkenes were investigated: (1) modified Henry reaction between arylnitromethanes and arylimines; and (2) Suzuki-Miyaura cross-coupling reaction of 2-aryl-1-bromo-1-nitroethenes with arylboronic acids. Some difficulty was encountered in the preparation of arylnitromethanes, thus leading to the exploration of a cross-coupling strategy that proved more useful. A Barton-Zard pyrrole cyclocondensation reaction between 1,2-diaryl-1-nitroethenes and N-methoxy-N-methyl-2-isocyanoacetamide gave the corresponding pyrrole Weinreb amides, which were then converted into the desired 3-pyrrolin-2-ones in two steps. Overall, this method allowed for the construction of 3,4-diaryl-3-pyrrolin-2-ones with complete regiocontrol of the substituents with respect to the lactam carbonyl. The utility of this synthetic methodology was demonstrated by the preparation of eight unsymmetrical and symmetrical 3,4-diaryl-3-pyrrolin-2-ones including the N-H lactam analog of the selective COX-II inhibitor, rofecoxib.
doi:10.1021/jo2013516
PMCID: PMC3193567  PMID: 21913662
19.  Three distinct amine receptors operating at different levels within the locomotory circuit are each essential for the serotonergic modulation of chemosensation in Caenorhabditis elegans 
Serotonin modulates behavioral plasticity in both vertebrates and invertebrates and in Caenorhabditis elegans regulates key behaviors, including locomotion, aversive learning and olfaction through at least four different 5-HT receptors. In the present study, we examined the serotonergic stimulation of aversive responses to dilute octanol in animals containing null alleles of these 5-HT receptors. Both ser-1 and mod-1 null animals failed to increase sensitivity to dilute octanol on food/5-HT, in contrast to wild-type, ser-4 or ser-7 null animals. 5-HT sensitivity was restored by the expression of MOD-1 and SER-1 in the AIB or potentially the AIY, and RIA interneurons of mod-1 and ser-1 null animals, respectively. Since none of these 5-HT receptors appear to be expressed in the ASH sensory neurons mediating octanol sensitivity, we identified a 5-HT6-like receptor, F16D3.7(SER-5), that was required for food/5-HT dependent increases in octanol sensitivity. ser-5 null animals failed to increase octanol sensitivity in the presence of food/5-HT and sensitivity could be restored by expression of SER-5 in the ASHs. Similarly, the RNAi knockdown of ser-5 expression in the ASHs of wild-type animals also abolished 5-HT dependent increases in octanol sensitivity, suggesting that SER-5 modulates the octanol responsiveness of the ASHs directly. Together, these results suggest that multiple amine receptors, functioning at different levels within the locomotory circuit, are each essential for the serotonergic modulation of ASH-mediated aversive responses.
doi:10.1523/JNEUROSCI.4585-08.2009
PMCID: PMC3418693  PMID: 19193891
ASH neuron; G-protein coupled receptors; locomotion; plasticity; reversals; serotonin (5-HT)
20.  The Therapeutic Relationship in E-Therapy for Mental Health: A Systematic Review 
Background
E-therapy is defined as a licensed mental health care professional providing mental health services via e-mail, video conferencing, virtual reality technology, chat technology, or any combination of these. The use of e-therapy has been rapidly expanding in the last two decades, with growing evidence suggesting that the provision of mental health services over the Internet is both clinically efficacious and cost effective. Yet there are still unanswered concerns about e-therapy, including whether it is possible to develop a successful therapeutic relationship over the Internet in the absence of nonverbal cues.
Objective
Our objective in this study was to systematically review the therapeutic relationship in e-therapy.
Methods
We searched PubMed, PsycINFO, and CINAHL through August 2011. Information on study methods and results was abstracted independently by the authors using a standardized form.
Results
From the 840 reviewed studies, only 11 (1.3%) investigated the therapeutic relationship. The majority of the reviewed studies were focused on the therapeutic alliance—a central element of the therapeutic relationship. Although the results do not allow firm conclusions, they indicate that e-therapy seems to be at least equivalent to face-to-face therapy in terms of therapeutic alliance, and that there is a relationship between the therapeutic alliance and e-therapy outcome.
Conclusions
Overall, the current literature on the role of therapeutic relationship in e-therapy is scant, and much more research is needed to understand the therapeutic relationship in online environments.
doi:10.2196/jmir.2084
PMCID: PMC3411180  PMID: 22858538
e-Therapy; therapeutic relationship; therapeutic alliance; common factors in psychotherapy
21.  The acute and preventative treatment of episodic migraine 
Annals of Indian Academy of Neurology  2012;15(Suppl 1):S33-S39.
Episodic migraine is a common debilitating condition with significant worldwide impact. An effective management plan must include acute treatment to relieve the pain and potential disability associated with the attacks and may also include preventative treatments with an aim of decreasing attack frequency and severity in the longer term. Acute treatments must be limited to a maximum of 2-3 days a week to prevent medication overuse headache and focus on simple analgesia, non-steroidal anti-inflammatory drugs and triptans. Preventative treatments are numerous and should be considered when migraine attacks are frequent and or disabling, acute medication is failing, in special circumstances such as hemiplegic migraines or if the patient requests them. All preventative medications must be given at therapeutic doses for at least 6-8 weeks before an adequate trial can be judged ineffective. The most important factor in choosing drugs is the patient and the clinical features of their attack and treatment should be tailored to these. Relative co-morbidities will influence drug choice, as will the side effect profile and the efficacy of the drug. First line preventative drugs include ß-blockers, amitriptyline and anti-epileptic drugs such as topiramate and valproate. Drugs with lower efficacy or poorer side effect profiles include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin and herbal medicines.
doi:10.4103/0972-2327.99998
PMCID: PMC3444218  PMID: 23024562
Acute; migraine; preventative; prophylaxis; treatment
22.  Retrospective Audit of Medication Order Turnaround Time after Implementation of Standardized Definitions 
Background:
Standardizing the interpretation of “stat”, “emergent”, “urgent”, and “now” medication orders can improve patient safety. However, the effect of implementing standardized definitions on the turnaround time for medication orders in hospital pharmacy dispensaries has not been studied.
Objectives:
To examine the effects of using formal definitions for “stat”, “emergent”, “urgent”, and “now” on turnaround time for medication orders within a pharmacy dispensary.
Methods:
Definitions for “stat”, “emergent”, “urgent”, and “now” orders, as well as for “turnaround time”, were developed from the formal literature and the grey literature. The definitions were implemented by educating all pharmacy staff. Retrospective audits of turnaround time were conducted at baseline (for all orders over a 1-month period) and after implementation of the definitions (for a total of 28 days over a 3-month period). Health records and medication orders were used to calculate time from prescribing to administration (total turnaround time) and time from prescribing to departure from the dispensary (dispensary turnaround time). Differences between total and dispensary turnaround times were compared with nonparametric statistics.
Results:
During the baseline audit period, 84 (1.1%) of 7787 orders were identified as “stat”, “emergent”, “urgent”, or “now”. After implementation of the formal definitions, 142 (2.6%) of 5365 orders were identified by one of these terms. The percentage of orders meeting the target dispensary turnaround time of less than 15 min was at least 90% both at baseline (76/84 [90%]) and after implementation (129/142 [91%]) (p = 0.80). Median dispensary turnaround time for stat and emergent medication orders combined (10 versus 9 min, p = 0.27) and for urgent and now medication orders combined (10 versus 12 min, p = 0.09) did not change after implementation of formal definitions. Similarly, median total turnaround time did not change for stat and emergent medication orders combined (30 versus 45 min, p = 0.32), but it increased for urgent and now orders combined (35 versus 45 min, p = 0.041).
Conclusions:
Implementing standardized definitions for “stat”, “emergent”, “urgent”, and “now” had no significant effect on dispensary turnaround time. However, the majority of orders with these designations met the expected target for dispensary turnaround time. Further interventions aimed at other health care professionals may be needed to reduce total turnaround time. This research supports the concept of interdisciplinary interventions for reducing total turnaround time.
PMCID: PMC3203827  PMID: 22479087
turnaround time; medication; stat; urgent; délai d’exécution; médicaments; stat; urgent
23.  Behavioral Signs of Schizoidia and Schizotypy in the Biological Parents of Social Anhedonics 
Behavior modification  2009;33(4):452-473.
A community sample of 88 putative schizotypes (48 social anhedonics, 40 controls), aged 18 to 19 years, and their biological parents (42 mothers of social anhedonics, 37 mothers of controls; 24 fathers of social anhedonics, 20 fathers of controls) receive videotaped diagnostic evaluations that serve as the basis for ratings of behavioral signs of schizoidia and schizotypy. Proband social anhedonics exhibit more atypical interpersonal behaviors characteristic of schizoid and schizotypal personality disorders than controls. Mothers of social anhedonics display more atypical interpersonal behaviors characteristic of schizotypal personality disorder than mothers of controls. In contrast, clinical symptom ratings of schizotypy do not differentiate mothers of social anhedonics from mothers of controls. Meaningful, though not statistically significant, effects are observed for behavioral sign ratings in the smaller sample of fathers of social anhedonics. Results provide preliminary support for the familiality of atypical interpersonal behavior in social anhedonics.
doi:10.1177/0145445509336431
PMCID: PMC2849114  PMID: 19436072
schizotypy; anhedonia; schizophrenia; behavior; interpersonal; family
24.  Development and Experimental Validation of a Predictive Threshold Cycle Equation for Quantification of Virulence and Marker Genes by High-Throughput Nanoliter-Volume PCR on the OpenArray Platform▿ † 
Applied and Environmental Microbiology  2008;74(12):3831-3838.
Development of quantitative PCR (QPCR) assays typically requires extensive screening within and across a given species to ensure specific detection and lucid identification among various pathogenic and nonpathogenic strains and to generate standard curves. To minimize screening requirements, multiple virulence and marker genes (VMGs) were targeted simultaneously to enhance reliability, and a predictive threshold cycle (CT) equation was developed to calculate the number of starting copies based on an experimental CT. The empirical equation was developed with Sybr green detection in nanoliter-volume QPCR chambers (OpenArray) and tested with 220 previously unvalidated primer pairs targeting 200 VMGs from 30 pathogens. A high correlation (R2 = 0.816) was observed between the predicted and experimental CTs based on the organism's genome size, guanine and cytosine (GC) content, amplicon length, and stability of the primer's 3′ end. The performance of the predictive CT equation was tested using 36 validation samples consisting of pathogenic organisms spiked into genomic DNA extracted from three environmental waters. In addition, the primer success rate was dependent on the GC content of the target organisms and primer sequences. Targeting multiple assays per organism and using the predictive CT equation are expected to reduce the extent of the validation necessary when developing QPCR arrays for a large number of pathogens or other targets.
doi:10.1128/AEM.02743-07
PMCID: PMC2446556  PMID: 18424532
25.  Effect of rhPDGF-BB Delivery on Mediators of Periodontal Wound Repair 
Tissue engineering  2006;12(6):1441-1450.
Growth factors such as platelet-derived growth factor (PDGF) exert potent effects on wound healing including the regeneration of tooth-supporting structures. This investigation examined the effect of the local delivery of PDGF-BB when combined with reconstructive periodontal surgery on local wound fluid (WF) levels of PDGF-AB, vascular endothelial growth factor (VEGF), and bone collagen telopeptide (ICTP) in humans with advanced periodontitis. Sixteen patients exhibiting localized periodontal osseous defects were randomized to one of three groups (β-TCP carrier alone, β-TCP + 0.3 mg/mL of recombinant human PDGF-BB [rhPDGF-BB], or β-TCP + 1.0 mg/mL of rhPDGF-BB) and monitored for 6 months. WF was harvested and analyzed for PDGF-AB, VEGF, and ICTP WF levels. Teeth contralateral to the target lesions served as controls. Increased levels of VEGF in the WF was observed for all surgical treatment groups with the 1.0 mg/mL rhPDGF-BB group showing the most pronounced difference at 3 weeks in the AUC analysis versus control (p < 0.0001). PDGF-AB WF levels were increased for the carrier alone group compared to both rhPDGF-BB groups. Low-dose rhPDGF-BB application elicited increases in ICTP at days 3–5 in the wound healing process, suggesting a promotion of bone turnover at early stages of the repair process (p < 0.02). These results demonstrate contrasting inducible expression patterns of PDGF-AB, VEGF, and ICTP during periodontal wound healing in humans.
doi:10.1089/ten.2006.12.1441
PMCID: PMC2586965  PMID: 16846342

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