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1.  Detection of soft tissue foreign bodies by nurse practitioner-performed ultrasound 
This study aimed to evaluate the accuracy of emergency nurse practitioner (NP)-performed point-of-care ultrasound (POCUS) for the detection of soft tissue foreign bodies (FBs).
Following a 2-h training session, ten NPs were assessed on their ability to detect various FBs in an experimental model. FBs (wood, metal and plastic) were inserted randomly into eight experimental models (uncooked chicken thighs) by an independent observer. Control experimental models had no FB inserted, but all had a 1-cm incision made on their surface. NPs, blinded to the type of model, were then assessed on their ability to detect the FBs by ultrasound examination using high-frequency linear transducers (Toshiba Nemio). Models were also scanned by two experienced emergency physicians (EPs) as a further control.
Overall, NP-performed POCUS detected 47 of the 60 foreign bodies with a sensitivity, specificity, positive predictive value and negative predictive value of 78.3%, 50%, 82% and 43%, respectively, compared with 83.3%, 75%, 90.9% and 60% for EPs. Sensitivity for detecting specific types of FB was 95%, 85% and 50% for wood, metal and plastic, respectively, for NP-performed POCUS, compared with 100%, 100% and 50% in the EP group.
NPs with no previous ultrasound experience can detect soft tissue FBs with accuracy comparable to that of EPs in an experimental model. Test sensitivity was high for wood and metal foreign bodies. Specificity was generally low.
PMCID: PMC3922659  PMID: 24476553
Nurse practitioners; Point-of-care ultrasound; Wound care; Foreign bodies; Diagnosis
2.  Epitope-Specific Mechanisms of IGF1R Inhibition by Ganitumab 
PLoS ONE  2013;8(2):e55135.
Therapeutic antibodies targeting the IGF1R have shown diverse efficacy and safety signals in oncology clinical trials. The success of these agents as future human therapeutics depends on understanding the specific mechanisms by which these antibodies target IGF1R signaling.
Methodology/Principal Findings
A panel of well-characterized assays was used to investigate the mechanisms by which ganitumab, a fully human anti-IGF1R antibody undergoing clinical testing, inhibits IGF1R activity. Epitope mapping using IGF1R subdomains localized the ganitumab binding site to the L2 domain. Binding of ganitumab inhibited the high-affinity interaction of IGF-1 and IGF-2 required to activate IGF1R in cells engineered for IGF1R hypersensitivity and in human cancer cell lines, resulting in complete blockade of ligand-induced cellular proliferation. Inhibition of IGF1R activity by ganitumab did not depend on endosomal sequestration, since efficient ligand blockade was obtained without evidence of receptor internalization and degradation. Clinically relevant concentrations of ganitumab also inhibited the activation of hybrid receptors by IGF-1 and IGF-2. Ganitumab was not an agonist of homodimeric IGF1R or hybrid receptors in MCF-7 and COLO 205 cells, but low-level IGF1R activation was detected in cells engineered for IGF1R hypersensitivity. This activation seems biologically irrelevant since ganitumab completely inhibited ligand-driven proliferation. The in vivo efficacy profile of ganitumab was equivalent or better than CR and FnIII-1 domain-specific antibodies, alone or in combination with irinotecan. CR domain-specific antibodies only blocked IGF-1 binding to IGF1R but were more potent than ganitumab at inducing homodimer and hybrid receptor downregulation in vitro, however this difference was less obvious in vivo. No inhibition of hybrid receptors was observed with the FnIII-1 domain antibodies, which were relatively strong homodimer and hybrid agonists.
The safety and efficacy profile of ganitumab and other anti-IGF1R antibodies may be explained by the distinct molecular mechanisms by which they inhibit receptor signaling.
PMCID: PMC3562316  PMID: 23383308
3.  The WISTAH hand study: A prospective cohort study of distal upper extremity musculoskeletal disorders 
Few prospective cohort studies of distal upper extremity musculoskeletal disorders have been performed. Past studies have provided somewhat conflicting evidence for occupational risk factors and have largely reported data without adjustments for many personal and psychosocial factors.
A multi-center prospective cohort study was incepted to quantify risk factors for distal upper extremity musculoskeletal disorders and potentially develop improved methods for analyzing jobs. Disorders to analyze included carpal tunnel syndrome, lateral epicondylalgia, medial epicondylalgia, trigger digit, deQuervain’s stenosing tenosynovitis and other tendinoses. Workers have thus far been enrolled from 17 different employment settings in 3 diverse US states and performed widely varying work. At baseline, workers undergo laptop administered questionnaires, structured interviews, two standardized physical examinations and nerve conduction studies to ascertain demographic, medical history, psychosocial factors and current musculoskeletal disorders. All workers’ jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of musculoskeletal disorders. Repeat nerve conduction studies are performed for those with symptoms of tingling and numbness in the prior six months. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. Case definitions have been established. Point prevalence of carpal tunnel syndrome is a combination of paraesthesias in at least two median nerve-served digits plus an abnormal nerve conduction study at baseline. The lifetime cumulative incidence of carpal tunnel syndrome will also include those with a past history of carpal tunnel syndrome. Incident cases will exclude those with either a past history or prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression.
A prospective cohort study of distal upper extremity musculoskeletal disorders is underway and has successfully enrolled over 1,000 workers to date.
PMCID: PMC3476983  PMID: 22672216
Epidemiology; Ergonomics; Cohort; Carpal tunnel syndrome; Strain index; TLV for HAL

Results 1-3 (3)