Evaluation of Indirect Methods for Motion Compensation in 2-D Focal Liver Lesion Contrast-Enhanced Ultrasound (CEUS) Imaging.

This study investigates the application and evaluation of existing indirect methods, namely point-based registration techniques, for the estimation and compensation of observed motion included in the 2-D image plane of contrast-enhanced ultrasound (CEUS) cine-loops recorded for the characterization and diagnosis of focal liver lesions (FLLs). The value of applying motion compensation in the challenging modality of CEUS is to assist in the quantification of the perfusion dynamics of an FLL in relation to its parenchyma, allowing for a potentially accurate diagnostic suggestion. Towards this end, this study also proposes a novel quantitative multi-level framework for evaluating the quantification of FLLs, which to the best of our knowledge remains undefined, notwithstanding many relevant studies. Following quantitative evaluation of 19 indirect algorithms and configurations, while also considering the requirement for computational efficiency, our results suggest that the "compact and real-time descriptor" (CARD) is the optimal indirect motion compensation method in CEUS.

Higher order genomic organization and epigenetic control maintain cellular identity and prevent breast cancer.

Cells establish and sustain structural and functional integrity of the genome to support cellular identity and prevent malignant transformation. In this review, we present a strategic overview of epigenetic regulatory mechanisms including histone modifications and higher order chromatin organization (HCO) that are perturbed in breast cancer onset and progression. Implications for dysfunctions that occur in hormone regulation, cell cycle control, and mitotic bookmarking in breast cancer are considered, with an emphasis on epithelial-to-mesenchymal transition and cancer stem cell activities. The architectural organization of regulatory machinery is addressed within the contexts of translating cancer-compromised genomic organization to advances in breast cancer risk assessment, diagnosis, prognosis, and identification of novel therapeutic targets with high specificity and minimal off target effects.

Automatic Identification of the Optimal Reference Frame for Segmentation and Quantification of Focal Liver Lesions in Contrast-Enhanced Ultrasound.

Post-examination interpretation of contrast-enhanced ultrasound (CEUS) cineloops of focal liver lesions (FLLs) requires offline manual assessment by experienced radiologists, which is time-consuming and generates subjective results. Such assessment usually starts by manually identifying a reference frame, where FLL and healthy parenchyma are well-distinguished. This study proposes an automatic computational method to objectively identify the optimal reference frame for distinguishing and hence delineating an FLL, by statistically analyzing the temporal intensity variation across the spatially discretized ultrasonographic image. Level of confidence and clinical value of the proposed method were quantitatively evaluated on retrospective multi-institutional data (n = 64) and compared with expert interpretations. Results support the proposed method for facilitating easier, quicker and reproducible assessment of FLLs, further increasing the radiologists' confidence in diagnostic decisions. Finally, our method yields a useful training tool for radiologists, widening CEUS use in non-specialist centers, potentially leading to reduced turnaround times and lower patient anxiety and healthcare costs.

Acute effects of a beverage containing bitter melon extract (CARELA) on postprandial glycemia among prediabetic adults.

BACKGROUND: Acute ingestion of bitter melon (BM) has been shown to suppress the postprandial glycemic response in diabetics, but its impact on glucose regulation among individuals with impaired glucose tolerance is unclear. Moreover, one's glucose tolerance level may influence the effectiveness of BM. This study aimed to examine the acute effects of a beverage containing BM extract on blood glucose regulation during an oral glucose tolerance test (OGTT) among prediabetics. METHODS: Ten prediabetic adults completed two OGTTs-glucose only (D2) and glucose+BM (D3). Responders were identified as subjects whose area under the glucose curve (AUCglu) during D3 was lower than D2. To compare the acute effects of the beverage among individuals with varying glucose tolerance levels, subjects were grouped by their glucose response pattern-Fastpeak (peak glucose (Glupeak) at 30 min postglucose (30P)) and Slowpeak (Glupeak after 30P). RESULTS: During D3, responders (n=5) experienced a 13.2% reduction in AUCglu (95% confidence interval (CI): -18.1% to -8.3%), 12.2% reduction in mean glucose (95% CI: -17.3% to -7.0%) and 10.6% reduction in Glupeak (95% CI: -17.5% to -3.7%); plasma glucose was reduced by 9.1% at 30P (95% CI: -15.6% to -2.6%), -24.0% at 60P (95% CI: -36.8% to -11.2%) and -20.0% at 90P (95% CI: -35.8% to -4.2%) during D3. No between-trial differences were noted for Fastpeak or Slowpeak. CONCLUSIONS: Acute ingestion of BM prior to the second OGTT (D3) led to a reduced postprandial glucose response in 50% of the subjects but did not affect the insulin response. Furthermore, the effectiveness of the beverage was seemingly uninfluenced by the subjects' glucose tolerance level. Although BM has shown to aid blood glucose management in diabetics, it remains uncertain why only a portion of subjects responded positively to the BM extract in the current study.

Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.

Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, resulted from a decrease in release probability and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to MIA, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders.

Oral simvastatin administration delays castration-resistant progression and reduces intratumoral steroidogenesis of LNCaP prostate cancer xenografts.

BACKGROUND: Growing evidence supports the idea that de novo steroidogenesis has an important role in prostate cancer's progression to the castration-resistant state following androgen deprivation therapy. Therefore, reducing the availability of cholesterol for use as a precursor in androgen synthesis may reduce proliferation and disease progression. METHODS: LNCaP xenograft-bearing mice were castrated and administered simvastatin via diet, and tumor volume and PSA concentration were monitored for 8 weeks post castration. Levels of serum and intratumoral androgens along with serum simvastatin and common toxicity markers were measured at end point. RESULTS: Reduced post-castration tumor growth rate in simvastatin-treated mice correlated with delayed time to castration-resistant progression, determined by two serum PSA doublings from post-castration nadir, when compared with xenografts in mice on control diet. At 8 weeks post castration, serum simvastatin levels were comparable to clinically relevant human doses with no evidence of overt muscle or liver toxicity. This suppressed post-castration tumor growth in the simvastatin diet group was correlated with reduced intratumoral testosterone and dihydrotestosterone levels. CONCLUSIONS: Reduced tumor growth and intratumoral androgen levels observed in simvastatin-treated, castrated mice harboring LNCaP xenograft suggests that suppressing de novo steroidogenesis can delay castration-resistant progression of this tumor model.

Achilles tendons from decorin- and biglycan-null mouse models have inferior mechanical and structural properties predicted by an image-based empirical damage model.

Achilles tendons are a common source of pain and injury, and their pathology may originate from aberrant structure function relationships. Small leucine rich proteoglycans (SLRPs) influence mechanical and structural properties in a tendon-specific manner. However, their roles in the Achilles tendon have not been defined. The objective of this study was to evaluate the mechanical and structural differences observed in mouse Achilles tendons lacking class I SLRPs; either decorin or biglycan. In addition, empirical modeling techniques based on mechanical and image-based measures were employed. Achilles tendons from decorin-null (Dcn(-/-)) and biglycan-null (Bgn(-/-)) C57BL/6 female mice (N=102) were used. Each tendon underwent a dynamic mechanical testing protocol including simultaneous polarized light image capture to evaluate both structural and mechanical properties of each Achilles tendon. An empirical damage model was adapted for application to genetic variation and for use with image based structural properties to predict tendon dynamic mechanical properties. We found that Achilles tendons lacking decorin and biglycan had inferior mechanical and structural properties that were age dependent; and that simple empirical models, based on previously described damage models, were predictive of Achilles tendon dynamic modulus in both decorin- and biglycan-null mice.

Comparison of a multifilament stainless steel suture with FiberWire for flexor tendon repairs--an in vitro biomechanical study.

Our goal was to investigate and compare the mechanical properties of multifilament stainless steel suture (MFSS) and polyethylene multi-filament core FiberWire in flexor tendon repairs. Flexor digitorum profundus tendons were repaired in human cadaver hands with either a 4-strand cruciate cross-lock repair or 6-strand modified Savage repair using 4-0 and 3-0 multifilament stainless steel or FiberWire. The multifilament stainless steel repairs were as strong as those performed with FiberWire in terms of ultimate load and load at 2 mm gap. This study suggests that MFSS provides as strong a repair as FiberWire. The mode of failure of the MFSS occurred by the suture pulling through the tendon, which suggests an advantage in terms of suture strength.

Safety net research in emergency medicine: proceedings of the Academic Emergency Medicine Consensus Conference on "The Unraveling Safety Net".

A primary goal of the Academic Emergency Medicine Consensus Conference, "The Unraveling Safety Net: Research Opportunities and Priorities," was to explore a formal research agenda for safety net research in emergency medicine. This paper represents the thoughts of active health services researchers regarding the structure and direction of such work, including some examples from their own research. The current system for safety net care is described, and the emergency department is conceptualized as a window on safety net patients and systems, uniquely positioned to help study and coordinate integrated processes of care.

Child health insurance outreach through the emergency department: a pilot study.

UNLABELLED: In 1997 the U.S. government funded the Children's Health Insurance Program (CHIP), but the 48 billion dollars initiative has had limited success in finding and enrolling uninsured children. While such children are more likely to receive care in emergency departments (EDs), no national initiative has targeted EDs for child health insurance outreach. OBJECTIVE: As a pilot study for a national multicenter study, this study evaluated the effectiveness of child health insurance outreach in an ED setting. METHODS: This was a prospective observational study of the outreach efforts of a single case manager from August 1998 to July 1999, performed at Foote Hospital ED in Jackson, Michigan (45,000 visits/year). All patients

Treatment resistant depression and axis I co-morbidity.

BACKGROUND: Treatment resistant depression (TRD) continues to present a formidable challenge to clinicians, accounts for over half of the annual costs associated with treatment for depression and causes great frustration to patients. Although there have been studies attempting to define TRD, little information is available as to the cause of TRD. One suggestion is that patients with TRD have a greater frequency of co-morbid psychiatric disorders, which explains their resistance to standard antidepressant treatments. The objective of this study was to compare the co-morbidity of Axis I disorders between a sample of TRD patients and a sample of non-TRD patients. METHODS: TRD and non-TRD patients, recruited from two separate antidepressant treatment studies, were assessed for Axis I co-morbidity using the SCID-P for the DSM-III-R. Patients for the two samples were then matched for baseline HAM-D-17 total score and gender. RESULTS: Results reveal that non-TRD patients had a higher rate of both lifetime and current generalized anxiety disorder co-morbidity than did the TRD patients. No other statistically significant differences in Axis I co-morbidity were found. CONCLUSIONS: These findings do not support the idea that current or lifetime Axis I co-morbidity is more common in TRD than non-TRD patients. In fact, the only statistical difference showed non-TRD patients with higher co-morbidity rates.

Coinfection with Campylobacter species: an epidemiological problem?

AIMS: To determine the frequency of coinfection with multiple strains in sporadic cases of human Campylobacter infection. METHOD AND RESULTS: During 1999 10 single colonies of Campylobacter were cultured from each of 53 positive faecal samples. Five isolates were taken from nonselective agar after passive filtration of faecal suspensions and five isolates were taken from selective agar plates. All isolates were sero- and phage typed and their antibiotic resistance determined. Pulsed-field gel electrophoresis and flagellin gene typing were performed on selected isolates. One patient was infected with Camp. coli, the remainder with strains of Camp. jejuni. The majority of patients was infected with a single strain of Campylobacter, but from each of four samples, 7.5%, two strains of Camp. jejuni, confirmed by molecular typing, were identified. CONCLUSION: Coinfection occurs in sporadic cases of campylobacteriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has implications in outbreak investigation when distinct strains have been isolated from epidemiologically related patients and/or the suspected source or vehicle.

Renal artery stenosis: duplex US after angioplasty and stent placement.

PURPOSE: To evaluate the hemodynamic outcome of technically successful percutaneous transluminal renal artery angioplasty and stent placement (PTRAS) with duplex ultrasonography (US). MATERIALS AND METHODS: Eighteen patients who underwent PTRAS in 22 renal arteries were prospectively examined. All had abnormal preprocedural duplex US findings. Those who had significant renal artery stenosis (>70%) at angiography and underwent technically successful percutaneous interventions were enrolled. Standard intrarenal duplex US parameters (acceleration index [AI], acceleration time, waveform morphology grade, and resistive index) were compared before and after interventions. RESULTS: A significant AI increase occurred after PTRAS (9.02 m/sec(2) +/- 4.85 [SD]), as compared with before intervention (2.34 m/sec(2) +/- 2.03; P <.001). Acceleration time significantly decreased from 0.084 second +/- 0.049 to 0.032 second +/- 0.008 (P <.01). There was also a significant resistive index increase from 0.69 +/- 0.12 to 0.79 +/- 0.12 (P <.01). Abnormal waveform morphology (modified Halpern waveform grade 3-6) was present in 19 (86%) of 22 intrarenal arteries prior to intervention, as compared with one (5%) after PTRAS (P <.001). In the instance in which an abnormal waveform persisted after intervention, waveform morphology improved from grade 6 to grade 3, with a concomitant AI increase from 0.96 to 5.1 m/sec(2). CONCLUSION: The findings suggest an important potential role for duplex US in noninvasive assessment of the immediate hemodynamic outcome and long-term follow-up of PTRAS.

Where health and welfare meet: social deprivation among patients in the emergency department.

CONTEXT: As a safety net provider for many disadvantaged Americans, the emergency department (ED) may be an efficient site not only for providing acute medical care, but also for addressing serious social needs. OBJECTIVE: To characterize the social needs of ED patients, and to evaluate whether the most disadvantaged patients have connections with the health and welfare system outside the ED. DESIGN: Cross-sectional survey conducted over 24 hours in the fall of 1997. SETTING: Three EDs: an urban public teaching hospital, a suburban university hospital, and a semirural community hospital. PARTICIPANTS: Consecutive patients presenting for care, including those transported by ambulance. The survey response rate was 91% (N = 300; urban = 115, suburban = 102, rural = 83). MAIN OUTCOME MEASURE: Index of socioeconomic deprivation described by the US Census Bureau (based on food, housing, and utilities). RESULTS: Of all ED patients, 31% reported one or more serious social deprivations. For example, 13% of urban patients reported not having enough food to eat, and 9% of rural patients reported disconnection of their gas or electricity (US population averages both less than 3%). While 40% of all patients had no consistent health care outside the ED (< or = 1 visit/year), those with higher levels of social deprivation had the least contact with the health care system outside the ED (P < .01). Although those with higher levels of deprivation were more likely to receive public assistance, still almost one-quarter of patients with high-level social deprivation were not receiving public aid. CONCLUSION: Many ED patients suffer from fundamental social deprivations that threaten basic health. The most disadvantaged of these patients frequently lack contact with other medical care sites or public assistance networks. Community efforts to address serious social deprivation should include partnerships with the local ED.

Plaque mineral induction and inhibition properties in the formation of supragingival calculus.

Several individual species of dental plaque bacteria have the ability to initiate the precipitation of calcium phosphate minerals in vitro; other plaque components have been shown to inhibit mineralisation. We have examined subjects' overall plaque mineralisation promoter and inhibitor properties, and have attempted to correlate them with supragingival calculus development over 6 months. Three-day-old plaque was collected from 22 adult subjects at the start and end of the study. To detect promoter activity, the plaque was placed in a suspension of brushite, the liquid phase of which was supersaturated with respect to hydroxyapatite. The extent of mineralisation was determined by the rise in phosphate concentration over 4 days. To detect inhibitor activity, plaque was placed in a similar suspension, which also contained hydroxyapatite. Promoter activity was compared with that hydroxyapatite, and inhibitor activity was compared with polyaspartate. The subjects' teeth were scaled at the start of the study, and calculus deposition was measured at the end using the Volpe Manhold method. Most plaque samples showed some promoter or inhibitor activity, or both, but no significant correlation existed between these activities and a subject's development of calculus. A significant inverse correlation existed between plaque mineralisation promoter activity and its inhibitor activity at the start of the study. Our results suggest that the nucleating and mineralisation inhibitory properties of young plaque will probably not be a useful target for a practical preventive methodology for supragingival calculus.

"Practicing" medicine without risk: students' and educators' responses to high-fidelity patient simulation.

PURPOSE: To understand the responses of medical students and educators to high-fidelity patient simulation, a new technology allowing "practice without risk." METHOD: Pilot groups of students (n = 27) and educators (n = 33) were exposed to a simulator session, then surveyed with multiple-choice and open-ended questions. Open-ended comments were transcribed and coded. They were analyzed for recurring themes and tested for inter-rater agreement. An independent focus group subsequently performed higher-level thematic analysis. RESULTS: Overall, 85% of the students rated the session excellent and 85% of the educators rated it excellent or very good. Over 80% of both groups thought that simulator-based training should be required for all medical students. Analytic categories derived from written comments were: Overall Assessment (i.e., "generally good experience"); Process Descriptors (i.e., "very realistic"); Teaching Utility (i.e., "broad educational tool"); Pedagogic Efficacy (i.e., "promotes critical thinking"); and Goals for Future Use (i.e., "more practice sessions"). Thirty percent of students and 38% of educators were impressed by the realism of the simulator, and they (37% and 25%, respectively) identified the ability to "practice" medicine as the primary advantage of simulation. The focus group rated cost as the major current disadvantage (66%). CONCLUSIONS: Students' and educators' responses to high-fidelity patient simulation were very positive. The ability to practice without risk must be weighed against the cost of this new technology.

Cost-benefit analysis of social work services in the emergency department: a conceptual model.

OBJECTIVE: To describe an economic model for formal cost-benefit analysis of emergency department (ED)-based social services. METHODS: The varied monetary costs and benefits associated with ED-based social work services were projected for three hypothetical levels of ED volume (30,000, 60,000, and 90,000 patients/year). Primary benefits included the prevention of return ED visits, the prevention of "social" hospital admissions, and the protection of doctor and nurse time. The primary cost was salary support for full-time social work staffing. Sensitivity analysis was performed to account for varying estimates. RESULTS: For a small-volume ED, total benefits to offset costs ranged from $43,869 to $81,504, yielding a net cost of $99,936 up to $137,571 for full-time social work coverage. For a moderate-size ED, total benefits ranged from $87,660 to $162,930, yielding a net cost of only $18,510 on the high end of the sensitivity analysis, and $87,668 on the low end. For a large-volume ED, total benefits ranged from $131,529 to $247,434, yielding a net cost of $49,911 on the low end of the sensitivity analysis, but a net benefit of $65,994 on the high end. CONCLUSIONS: Dedicated social work staffing of EDs may yield net economic benefits, especially in large urban centers. Moderate-size EDs may almost "break even" in economic terms, and small EDs may realize a net cost, but in either case, the cost of social services can be significantly offset by decreased utilization of hospital and ED services, and by more efficient use of medical staff time.

Preventive care in the emergency department, Part I: Clinical preventive services--are they relevant to emergency medicine? Society for Academic Emergency Medicine Public Health and Education Task Force Preventive Services Work Group.

In 1998 the Society for Academic Emergency Medicine's (SAEM's) Board of Directors asked the SAEM Public Health and Education Task Force to develop recommendations for prevention, screening, and counseling activities to be conducted in emergency departments (EDs). The Task Force's work was divided into two phases: 1) a discussion of the rationale for preventive services in the ED, along with generation of a preliminary list of prevention activities that could be studied for ED implementation; and 2) a formal evidence-based review of topics chosen from the preliminary list, along with recommendations for ED implementation and further study. This paper represents Phase I of the project. Phase II, the formal evidence-based review and recommendations, is published separately in this issue.