A new measure to understand the role of science in US Congress: lessons learned from the Legislative Use of Research Survey (LURS).

Background: There is growing interest in and recognition of the need to use scientific evidence to inform policymaking. However, many of the existing studies on the use of research evidence (URE) have been largely qualitative, and the majority of existing quantitative measures are underdeveloped or were tested in regional or context-dependent settings. We are unaware of any quantitative measures of URE with national policymakers in the US. Aims and objectives: Explore how to measure URE quantitatively by validating a measure of congressional staff's attitudes and behaviors regarding URE, the Legislative Use of Research Survey (LURS), and by discussing the lessons learned through administering the survey. Methods: A 68-item survey was administered to 80 congressional staff to measure their reported research use, value of research, interactions with researchers, general information sources, and research information sources. Confirmatory factor analyses were conducted on each of these five scales. We then trimmed the number of items, based on a combination of poor factor loadings and theoretical rationale, and ran the analyses on the trimmed subscales. Findings: We substantially improved our model fits for each scale over the original models and all items had acceptable factor loadings with our trimmed 35-item survey. We also describe the unique set of challenges and lessons learned from surveying congressional staff. Discussion and conclusions: This work contributes to the transdisciplinary field of URE by offering a tool for studying the mechanisms that can bridge research and policy and shedding light into best practices for measuring URE with national policymakers in the US.

[E-cigarette use among cannabis users and multi-users of psychoactive products: A cohort study]. / L'usage d'e-cigarette chez les usagers de cannabis et les polyconsommateurs : étude de cohorte.

INTRODUCTION: There is no evidence in the literature relating to the evolution of e-cigarette use among cannabis users and multi-users (of alcohol, tobacco or cannabis). OBJECTIVE: To describe the evolution over 12 months of e-cigarette use in cannabis users and multi-users. METHODS: A prospective observational cohort study in general practice, between 2015 and 2016. RESULTS: A total of 4.8% of monitored cannabis users remained or became current users of e-cigarettes by the end of the monitoring period versus 4.5% among non-users of cannabis, with no statistically significant difference. A total of 5.1% of monitored multi-users remained or became current users of e-cigarettes by the end of the monitoring period versus 2.4% among the non-multi-users, with no statistically significant difference. Cannabis users and multi-users reported more e-cigarette experimentation through curiosity and following someone's suggestion, compared to non-cannabis users or non multi-users. No statistically significant association was found between cannabis or multi-drug use and staying or becoming a current e-cigarette user over 12 months. CONCLUSION: Cannabis users and multi-users would tend to experiment with e-cigarettes more than other patients but this use would not be sustained.

Vestibular dysfunction in patients with chronic pain or underlying neurologic disorders.

CONTEXT: Individuals with vestibular dysfunction are at increased risk for falling. In addition, vestibular dysfunction is associated with chronic pain, which could present a serious public health concern as approximately 43% of US adults have chronic pain. OBJECTIVE: To assess the incidence of vestibular dysfunction in patients receiving medication for chronic, noncancer pain or other underlying neurologic disorders and to determine associated follow-up therapeutic and diagnostic recommendations. METHODS: The authors conducted a retrospective medical record review of consecutive patients who were treated in their private neuroscience practice with medications for chronic pain or underlying neurologic disorders in 2011. All patients underwent a series of tests using videonystagmography for the assessment of vestibular function. Test results and recommendations for therapy and additional testing were obtained. RESULTS: Medical records of 124 patients (78 women, 46 men) were reviewed. Vestibular deficits were detected in 83 patients (66.9%). Patient ages ranged from 29 through 72 years, with a mean age of 50.7 years for women and 52.5 years for men. Physician-recommended therapy and follow-up testing were as follows: 32 patients (38.6%), neurologic examination and possible magnetic resonance (MR) imaging or computed tomography (CT) of the brain; 26 patients (31.3%), vestibular rehabilitation therapy only; 22 patients (26.5%), vestibular and related balance-function rehabilitation therapy, further neurologic examination, and possible MR imaging or CT; 2 patients (2.4%), balance-function rehabilitation therapy and specialized internal auditory canal high-magnification MR imaging or CT to assess for acoustic neuroma; and 1 patient (1.2%), specialized internal auditory canal high-magnification MR imaging or CT to evaluate for possible intracanalicular acoustic neuroma. CONCLUSION: Patients being treated with medications for chronic, noncancer pain or other underlying neurologic disorders may have a higher-than-average incidence of vestibular dysfunction. Baseline assessment and monitoring of the vestibular apparatus may be indicated for these patients.

[Rethinking the place of primary healthcare in France--role of general practice]. / Repenser la place des soins de santé primaires en France--Le rôle de la médecine générale.

Primary healthcare is poorly structured in France while it is well defined at the international level: it is the point of first medical contact of the population with the healthcare system. General practice is the clinical specialty oriented to primary healthcare. Data in the scientific literature highlight the need of refocusing the health system on primary care known to improve both morbi-mortality and care efficiency. In France, health authorities acknowledge general practitioners as playing a key role in the health care system: its time to move from intention to action. Structural changes are needed to achieve this reinforcement of primary healthcare: to re-orientate medical studies towards primary care; to develop research in primary care; to promote cooperation between care providers; to ease the daily workload of practitioners; to diversify methods of payment; to propose a guide for patient's use of primary care. The transformation of the healthcare system in France requires a real strategy of primary healthcare implementation. Regardless of financial constraints, it is possible to redistribute the resources towards ambulatory care. Strengthening the role of general practice and favoring its societal recognition will be the major stages of this change.

Scoliosis rates in symptomatic patients as demonstrated with weight-bearing or supine MR imaging.

CONTEXT: In the United States an estimated 6 million persons are affected by scoliosis, which is characterized by a 3-dimensional deformity of the spine that involves a curvature in the sagittal, frontal, and transverse planes. OBJECTIVE: To determine the rates of scoliosis in patients with spine-related pain unassociated with cancer, as demonstrated by magnetic resonance (MR) images obtained with patients in either a weight-bearing or a supine position. METHODS: The authors conducted a retrospective review of MR images obtained during a 2-year period in patients referred because of symptoms of radiculopathy or other spine-related pain unassociated with cancer and unresolved after conservative treatment. Images were obtained either with the patient supine or with the patient in a weight-bearing, seated position, and all images were reviewed by a neuroimaging physician. Scoliosis was assessed according to the Cobb angle method. RESULTS: A total of 1982 MR images from 1486 patients were reviewed. Of those, 986 images in 761 patients were obtained with a low-field-strength (0.3-T) MR imager with the patient supine, and 996 images in 725 patients were obtained with a mid-field-strength (0.6-T) MR imager with the patient in a weight-bearing, seated position. Scoliosis (dextroscoliosis, levoscoliosis, or both) was identified in 958 MR images (48.3%), of which 779 (78.2%) were obtained with patients in a weight-bearing position and 179 (18.2%) were obtained with patients in a supine position. CONCLUSION: The scoliosis rate was lower in the supine MR imaging group than in the weight-bearing MR imaging group. Scoliosis rates may be affected by the position in which the patient is examined, with the possibility that the weight-bearing position differentially exposes scoliosis, compared with the supine position.

Lumbar stenosis rates in symptomatic patients using weight-bearing and recumbent magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to determine the rate of lumbar stenosis detected via magnetic resonance imaging (MRI) in patients with symptomatic foraminal stenosis, lateral recess stenosis, or central stenosis. METHODS: A retrospective review was performed on 1983 MRI scans from a 2-year period on 1486 symptomatic patients. Of these patients, 761 were scanned in the recumbent position using low-field (0.3 T, Airis II; Hitachi, Twinsburg, Ohio) MRI, and 725 were scanned in an upright sitting position using midfield (0.6 T) open Upright MRI (Fonar Corp, Melville, NY). In total, 986 serial scans (recumbent) and 997 serial scans (weight-bearing) were performed. RESULTS: Of scans performed in the recumbent position, stenoses were identified in 382 scans (38.8%), central stenosis in 119 scans (12%), lateral recess stenosis in 91 scans (9.2%), and foraminal stenosis in 327 scans (33.2%). Of scans performed in a weight-bearing position, stenoses were identified in 565 scans (56.7%), central stenosis in 136 scans (13.6%), lateral recess stenosis in 206 scans (20.7%), and foraminal stenosis in 524 scans (52.6%). CONCLUSIONS: The stenosis rates as indicated by MRI interpretation ranged between 38.5% (recumbent) and 56.7% (weight-bearing). These rates are higher than those reported in the medical literature for asymptomatic patients. Further study is needed to determine whether weight-bearing, compared with recumbent, MRI better informs the clinician in the diagnosis of spinal stenosis.

Lumbar disk protrusion rates of symptomatic patients using magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to determine the rate of disk protrusions detected via magnetic resonance imaging (MRI) in patients symptomatic for spine pain, radiculopathy, or other spine-related pain. METHODS: A retrospective review of 1983 MRI scans was performed over a 2-year period on 1486 patients, each of whom was symptomatic for spine pain, radiculopathy, or other noncancer, spine-related pain. Of these patients, 761 were scanned in the recumbent position using low-field (0.3 T, Airis II, Hitachi, Twinsburg, Ohio) MRI, and 725 were scanned in an upright, sitting position using mid-field (0.6 T) open Upright MRI (Fonar, Melville, NY). In total, 986 serial scans were performed on patients in the recumbent position and 997 serial scans on patients in the weight-bearing position. RESULTS: One or more disk protrusions were identified in 73.3% of scans performed in the sitting position and in 50.1% of scans performed in the recumbent position. Most disk protrusions occurred at L5-S1 (52.3% and 29.8%), L4-L5 (42.6% and 26.7%), and L3-L4 (26.7% and 13.1%) in upright and recumbent positions, respectively. CONCLUSIONS: The disk protrusion rate in this group of patients ranged between 50.1% (recumbent) and 73.3% (weight-bearing). These rates are higher than rates reported in the medical literature for asymptomatic patients, a finding that supports the decision to further evaluate patients with persistent spine-related pain.

An evaluation of a computer based education program for the diagnosis and management of dementia in primary care. An international study of the transcultural adaptations necessary for European dissemination.

OBJECTIVES: The aim of this study is to make an inventory of the changes that are needed to make an interactive computer based training program (ICBT) with a specific educational content, acceptable to professional communities with different linguistic,cultural and health care backgrounds in different European countries. METHODS: Existing educational software, written in two languages was reviewed by GPs and primary care professionals in three different countries. Reviewers worked through the program using a structured critical reading grid. RESULTS: A 'simple' translation of the program is not sufficient. Minor changes are needed to take account of linguistic differences and medical semantics. Major changes are needed in respect of the existing clinical guidelines in every country related to differences in the existing health care systems. CONCLUSIONS: ICTB programs cannot easily be used in different countries and cultures. The development of a structured educational program needs collaboration between educationalists, domain experts, information technology advisers and software engineers. Simple validation of the content by local expert groups will not guarantee the program's exportability. It is essential to involve different national expert groups at every phase of the development process in order to disseminate it in other countries.

The validity of clinical diagnoses of dementia in a group of consecutively autopsied memory clinic patients.

BACKGROUND: Epidemiological studies show that up to 10% of individuals aged 65 years and older suffer from dementia, most commonly from dementia of the Alzheimer Type (DAT) (1). Clinicopathological studies are critical to our understanding of this disease and improving the accuracy of clinical diagnoses. OBJECTIVES: Our objectives were to examine the validity of clinical diagnoses of DAT, to determine the prevalence of different forms of dementia in this sample, and to investigate the relationship between age at death and polymorbidity. SUBJECTS AND METHOD: Clinical data were available from 221 patients who had been examined at the Basel Memory Clinic between 1986 and 1996. From this population, 34% (75 patients) were autopsied in the Department of Pathology, University Hospital Basel, and neuropathological examinations were additionally performed on 62 (83%) of these patients. Clinical and neuropathological data were retrospectively compared. RESULTS: 67.8% of the neuropathologically examined patients received a definitive diagnosis of AD (Alzheimer's disease), vascular dementia (VaD) or mixed dementia (AD and VaD). AD alone or with other histopathological hallmarks of dementia was the most prevalent neuropathological diagnosis (63%). VaD was deemed the only cause of dementia in only 4.8% of patients. The sensitivity for DAT was 75.9%, the specificity 60.6%. Increasing age was associated with an increasing number of clinical and neuropathological diagnoses. CONCLUSION: The sensitivity and specificity of the clinical diagnoses of DAT found in our study are similar to previous reports (2-5). Older patients had more etiologies of their dementia than younger patients. This study reaffirms the need for internationally accepted criteria for clinical and neuropathological diagnoses, as well as further clinical-neuropathological investigations to further refine the clinical diagnostic process.

Convergent synthesis of potent peptide inhibitors of the Grb2-SH2 domain by palladium catalyzed coupling of a terminal alkyne.

A new strategy was developed to prepare in a very efficient and convergent manner C-terminal modified tripeptides with high affinities for the Grb2-SH2 domain. Using Pd(PPh3)2Cl2 as catalyst, selected naphthyl iodides and triflates were coupled to Ac-Pmp(t-Bu)2-Ac6c-Asn-NH(prop-2-ynyl). The resulting alkyne derivatives were hydrogenated and deprotected to afford potent Grb2-SH2 inhibitors.

Immunoreactive domains and integrin-binding motifs in adenovirus penton base capsomer.

A panel of nine independent mouse monoclonal antibodies (MAbs) against penton base capsomers of subgenus C adenovirus serotypes 2 (Ad2) and 5 (Ad5) were isolated and characterized. Two of them (1D2 and 5A5), raised against Ad5 virion as the immunogen, bound to sodium dodecyl sulfate (SDS)-resistant and subgenus C-specific epitopes that were not present in subgenus B Ad3 penton base. The 1D2 and 5A5 epitopes were mapped to two distinct regions that did not belong to the main variable region carrying the integrin-binding RGD motif at position 340. For the other seven MAbs, raised against recombinant Ad2 penton base protein (9S-pentamers), the epitopes were sensitive to SDS-denaturation, but reacted with native Ad2, Ad5, and Ad3 penton base. The epitopes recognized by the nine MAbs and by polyclonal antipenton base antibodies defined three major immunoreactive regions. One (I) mapped to the N-terminal domain (residues 116-165); the other two regions were almost symmetrically disposed on both sides of the integrin-binding RGD motif at position 340, within residues 248-270 (II), and within residues 368-427 (III) in the C-terminal domain. Region II overlapped the fiber-binding site in penton base (residues 254-260). None of the MAbs showed any detectable virus neutralization effect, but they all slightly augmented the efficiency of Ad-mediated gene transfer. Although none of their epitopes included the RGD-340 tripeptide, substitutions of the arginine residue in the RGD motif abolished the reactivity of six individual and distant epitopes, suggesting a major conformational role for the RGD-containing domain.

Structure-based design and synthesis of phosphinate isosteres of phosphotyrosine for incorporation in Grb2-SH2 domain inhibitors. Part 1.

Based on X-ray crystal structure information, mono charged phosphinate isosteres of phosphotyrosine have been designed and incorporated in a short inhibitory peptide sequence of the Grb2-SH2 domain. The resulting compounds, by exploiting additional interactions, inhibit binding to the Grb2-SH2 domain as potently as the corresponding doubly charged (phosphonomethyl)phenylalanine analogue.

Structure-based design and synthesis of phosphinate isosteres of phosphotyrosine for incorporation in Grb2-SH2 domain inhibitors. Part 2.

A series of novel phosphinates, derived from 4-phosphonomethylphenylalanine, are described as isosteres of phosphotyrosine. Benzyl (or alkyl) phosphinomethylphenylalanine derivatives were prepared by alkylation of an amino acid P-H phosphinate.

Sequence requirement for the nucleolar localization of human I-mfa domain-containing protein (HIC p40).

The human I-mfa domain-containing protein (HIC) mRNA produces two protein isoforms, HIC p32 and p40, synthesized from alternative translational initiations. p32 translation is initiated from a standard AUG codon and p40 is an N-terminal extension of p32 generated from an upstream GUG codon. The two isoforms show different subcellular localization: p32 is distributed throughout the cytoplasm whereas p40 can be found both in the cytoplasm and the nucleolus. To investigate the possibility that p40 contains a nucleolus targeting sequence in its N-terminal region, COS cells were transfected with an eukaryotic expression vector coding for green fluorescent protein (GFP) fused to the p40 N terminus. The localization of this fusion protein in the nucleolus indicated that the N-terminal amino acids of p40 probably contain a nucleolar localization signal (NoLS). To find the structural motifs required for nucleolar localization of p40, deletion mutants were expressed in COS cells as fusion polypeptides with GFP. We defined a domain of 19 amino acids near the N terminus that contains an arginine-rich subdomain that conforms to other known NoLS. To demonstrate that this sequence is an authentic NoLS, the sequence was fused to GFP. This fusion protein was observed to migrate into the nucleolus. Taken together, our studies demonstrate that p40 contains a NoLS.