Sonification of Genomic Data to Represent Genetic Load in Zoo Populations.

Maintaining a diverse gene pool is important in the captive management of zoo populations, especially in endangered species such as the pink pigeon (Nesoenas mayeri). However, due to the limited number of breeding individuals and relaxed natural selection, the loss of variation and accumulation of harmful variants is inevitable. Inbreeding results in a loss of fitness (i.e., inbreeding depression), principally because related parents are more likely to transmit a copy of the same recessive deleterious genetic variant to their offspring. Genomics-informed captive breeding can manage harmful variants by artificial selection, reducing the genetic load by avoiding the inheritance of two copies of the same harmful variant. To explain this concept in an interactive way to zoo visitors, we developed a sonification game to represent the fitness impacts of harmful variants by detuning notes in a familiar musical melody (i.e., Beethoven's Für Elise). Conceptually, zoo visitors play a game aiming to create the most optimal pink pigeon offspring in terms of inbreeding depression. They select virtual crosses between pink pigeon individuals and listen for the detuning of the melody, which represents the realised load of the resultant offspring. Here we present the sonification algorithm and the results of an online survey to see whether participants could identify the most and least optimal offspring from three potential pink pigeon offspring. Of our 98 respondents, 85 (86.7%) correctly identified the least optimal offspring, 73 (74.5%) correctly identified the most optimal, and 62 (63.3%) identified both the most and least optimal offspring using only the sonification.

Using sound to understand protein sequence data: new sonification algorithms for protein sequences and multiple sequence alignments.

BACKGROUND: The use of sound to represent sequence data-sonification-has great potential as an alternative and complement to visual representation, exploiting features of human psychoacoustic intuitions to convey nuance more effectively. We have created five parameter-mapping sonification algorithms that aim to improve knowledge discovery from protein sequences and small protein multiple sequence alignments. For two of these algorithms, we investigated their effectiveness at conveying information. To do this we focussed on subjective assessments of user experience. This entailed a focus group session and survey research by questionnaire of individuals engaged in bioinformatics research. RESULTS: For single protein sequences, the success of our sonifications for conveying features was supported by both the survey and focus group findings. For protein multiple sequence alignments, there was limited evidence that the sonifications successfully conveyed information. Additional work is required to identify effective algorithms to render multiple sequence alignment sonification useful to researchers. Feedback from both our survey and focus groups suggests future directions for sonification of multiple alignments: animated visualisation indicating the column in the multiple alignment as the sonification progresses, user control of sequence navigation, and customisation of the sound parameters. CONCLUSIONS: Sonification approaches undertaken in this work have shown some success in conveying information from protein sequence data. Feedback points out future directions to build on the sonification approaches outlined in this paper. The effectiveness assessment process implemented in this work proved useful, giving detailed feedback and key approaches for improvement based on end-user input. The uptake of similar user experience focussed effectiveness assessments could also help with other areas of bioinformatics, for example in visualisation.

Assessing the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator.

BACKGROUND: The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter-defibrillator (ICD) that was "non-MRI-conditional" (i.e., not approved by the Food and Drug Administration for MRI scanning). METHODS: Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. RESULTS: MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self-terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P-wave and R-wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. CONCLUSIONS: In this study, device or lead failure did not occur in any patient with a non-MRI-conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361 .).

Food cravings: Associations with dietary intake and metabolic health.

Food cravings are a desire for specific foods which, if uncontrolled may lead to excess energy intake and weight gain. However, information on the relation between food cravings, dietary intake, and indices of metabolic health is limited. This study used baseline data from females (n = 229; aged 40.9 ± 0.7 years; BMI 34.7 ± 6.4 kg/m2) who were dependents of active duty and retired military personnel, and enrolled in the Healthy Families Healthy Forces weight loss and maintenance study. Measures obtained included food cravings using the Food Craving Questionnaire-Trait (which provides a habitual and stable measure of food cravings), dietary composition and eating patterns from three 24-h dietary recalls and the Stanford 7-day Physical Activity Recall, body composition from anthropometric measures, cardiometabolic risk factors from blood measures, and demographic information from questionnaires. Linear, quantile, or logistic regression models were used to examine the association of total food craving scores on dietary intake, and indices of metabolic health. In individuals reporting plausible energy intake (n = 146; 2210 ± kcals/day) higher food craving scores were associated with a lower diet quality (P < 0.05), higher eating frequency (P = 0.02), longer daily eating interval (P < 0.05), and a lower likelihood of following a time restricted eating pattern (P = 0.02). Food cravings were also positively associated with BMI (P = 0.03) and waist circumference (P = 0.01), but not with measures of cardiometabolic risk (LDL, HDL, total cholesterol:HDL, triglycerides, glucose, glycated hemoglobin, insulin and C-reactive protein concentrations, blood pressure, metabolic syndrome). Our findings of significant associations of food cravings with lower diet quality, poor eating patterns, and unfavorable body composition strongly support efforts of targeting cravings in behavioral programs for weight management.

Linker engineering in anti-TAG-72 antibody fragments optimizes biophysical properties, serum half-life, and high-specificity tumor imaging.

Antibody (Ab) fragments have great clinical potential as cancer therapeutics and diagnostics. Their small size allows for fast clearance from blood, low immunoreactivity, better tumor penetration, and simpler engineering and production. The smallest fragment derived from a full-length IgG that retains binding to its antigen, the single-chain variable fragment (scFV), is engineered by fusing the variable light and variable heavy domains with a peptide linker. Along with switching the domain orientation, altering the length and amino acid sequence of the linker can significantly affect scFV binding, stability, quaternary structure, and other biophysical properties. Comprehensive studies of these attributes in a single scaffold have not been reported, making design and optimization of Ab fragments challenging. Here, we constructed libraries of 3E8, an Ab specific to tumor-associated glycoprotein 72 (TAG-72), a mucinous glycoprotein overexpressed in 80% of adenocarcinomas. We cloned, expressed, and characterized scFVs, diabodies, and higher-order multimer constructs with varying linker compositions, linker lengths, and domain orientations. These constructs dramatically differed in their oligomeric states and stabilities, not only because of linker and orientation but also related to the purification method. For example, protein L-purified constructs tended to have broader distributions and higher oligomeric states than has been reported previously. From this library, we selected an optimal construct, 3E8.G4S, for biodistribution and pharmacokinetic studies and in vivo xenograft mouse PET imaging. These studies revealed significant tumor targeting of 3E8.G4S with a tumor-to-background ratio of 29:1. These analyses validated 3E8.G4S as a fast, accurate, and specific tumor-imaging agent.

The global cardiovascular magnetic resonance registry (GCMR) of the society for cardiovascular magnetic resonance (SCMR): its goals, rationale, data infrastructure, and current developments.

BACKGROUND: With multifaceted imaging capabilities, cardiovascular magnetic resonance (CMR) is playing a progressively increasing role in the management of various cardiac conditions. A global registry that harmonizes data from international centers, with participation policies that aim to be open and inclusive of all CMR programs, can support future evidence-based growth in CMR. METHODS: The Global CMR Registry (GCMR) was established in 2013 under the auspices of the Society for Cardiovascular Magnetic Resonance (SCMR). The GCMR team has developed a web-based data infrastructure, data use policy and participation agreement, data-harmonizing methods, and site-training tools based on results from an international survey of CMR programs. RESULTS: At present, 17 CMR programs have established a legal agreement to participate in GCMR, amongst them 10 have contributed CMR data, totaling 62,456 studies. There is currently a predominance of CMR centers with more than 10 years of experience (65%), and the majority are located in the United States (63%). The most common clinical indications for CMR have included assessment of cardiomyopathy (21%), myocardial viability (16%), stress CMR perfusion for chest pain syndromes (16%), and evaluation of etiology of arrhythmias or planning of electrophysiological studies (15%) with assessment of cardiomyopathy representing the most rapidly growing indication in the past decade. Most CMR studies involved the use of gadolinium-based contrast media (95%). CONCLUSIONS: We present the goals, mission and vision, infrastructure, preliminary results, and challenges of the GCMR. TRIAL REGISTRATION: Identification number on ClinicalTrials.gov: NCT02806193 . Registered 17 June 2016.

Feasibility of a multimodal (18)F-FDG-directed lymph node surgical excisional biopsy approach for appropriate diagnostic tissue sampling in patients with suspected lymphoma.

BACKGROUND: F-FDG PET/CT imaging is widely utilized in the clinical evaluation of patients with suspected or documented lymphoma. The aim was to describe our cumulative experience with a multimodal (18)F-FDG-directed lymph node surgical excisional biopsy approach in patients with suspected lymphoma. METHODS: Thirteen patients (mean age 51 (± 16;22-76) years), with suspected new or suspected recurrent lymphoma suggested by (18)F-FDG-avid lesions seen on prior diagnostic whole-body PET/CT imaging, were injected IV with (18)F-FDG prior to undergoing same-day diagnostic lymph node surgical excisional biopsy in the operating room. Various (18)F-FDG detection strategies were used on the day of surgery, including, (1) same-day pre-resection patient PET/CT; (2) intraoperative gamma probe assessment; (3) clinical scanner specimen PET/CT imaging of whole surgically excised tissue specimens; (4) specimen gamma well counts; and/or (5) same-day post-resection patient PET/CT. RESULTS: Same-day (18)F-FDG injection dose was 14.8 (± 2.4;12.5-20.6) millicuries or 548 (± 89;463-762) megabecquerels. Sites of (18)F-FDG-avid lesions were 4 inguinal, 3 cervical, 3 abdominal/retroperitoneal, 2 axillary, and 1 gluteal region subcutaneous tissue. Same-day pre-resection patient PET/CT was performed on 6 patients. Intraoperative gamma probe assessment was performed on 13 patients. Clinical scanner PET/CT imaging of whole surgically excised tissue specimens was performed in 10 cases. Specimen gamma well counts were performed in 6 cases. Same-day post-resection patient PET/CT imaging was performed on 8 patients. Time from (18)F-FDG injection to same-day pre-resection patient PET/CT, intraoperative gamma probe assessment, and same-day post-resection patient PET/CT were 76 (± 8;64-84), 240 (± 63;168-304), and 487 (± 104;331-599) minutes, respectively. Time from (18)F-FDG injection to clinical scanner PET/CT of whole surgically excised tissue specimens was 363 (± 60;272-446) minutes. Time from (18)F-FDG injection to specimen gamma well counts was 591 (± 96;420-689) minutes. Intraoperative gamma probe assessment successfully identified (18)F-FDG-avid lesions in 12/13 patients. Histopathologic evaluation confirmed lymphoma in 12/13 patients and benign disease in 1/13 patients. CONCLUSIONS: A multimodal approach to (18)F-FDG-directed lymph node surgical excisional biopsy for suspected lymphoma is technically feasible for guiding appropriate diagnostic tissue sampling of lymph nodes seen as (18)F-FDG-avid lesions on diagnostic (18)F-FDG PET/CT imaging.

MEDICAL BRIGADES, GLOBAL HEALTH AND THE UNITED NATIONS: MILLENNIUM DEVELOPMENT GOALS AND DEVELOPING NATIONS.

Recently, recommendations have been made that global health initiatives change their focus from disease specific intervention to bolstering health systems and general health care. The aim of this is to ultimately increase access to primary care, clean water, education, hygiene, and prevent malnutrition, among other goals. While many major global health initiatives have followed this trend, so have many smaller scale programs including short-term medical brigades. Despite a trending increase in the number of privately run short-term medical brigades, until recently, little research has been done on the potential positive and negative effects that can arise from such programs. Now, guidelines have been initiated to create well-structured programs. When followed, these smaller scale initiatives can be successful in helping increase access to healthcare, sustainably strengthening communities in terms of general health. While recent legislation in the United States has addressed domestic policy in the Patient Protection Affordable Care Act of 2010 (ACA), the ACA should also consider some of the basic "sustainable" policies being implemented by international health care providers.

Comparison of two threshold detection criteria methodologies for determination of probe positivity for intraoperative in situ identification of presumed abnormal 18F-FDG-avid tissue sites during radioguided oncologic surgery.

BACKGROUND: Intraoperative in situ identification of (18)F-FDG-avid tissue sites during radioguided oncologic surgery remains a significant challenge for surgeons. The purpose of our study was to evaluate the 1.5-to-1 ratiometric threshold criteria method versus the three-sigma statistical threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ identification of presumed abnormal (18)F-FDG-avid tissue sites in a manner that was independent of the specific type of gamma detection probe used. METHODS: From among 52 patients undergoing appropriate in situ evaluation of presumed abnormal (18)F-FDG-avid tissue sites during (18)F-FDG-directed surgery using 6 available gamma detection probe systems, a total of 401 intraoperative gamma detection probe measurement sets of in situ counts per second measurements were cumulatively taken. RESULTS: For the 401 intraoperative gamma detection probe measurement sets, probe positivity was successfully met by the 1.5-to-1 ratiometric threshold criteria method in 150/401 instances (37.4%) and by the three-sigma statistical threshold criteria method in 259/401 instances (64.6%) (P < 0.001). Likewise, the three-sigma statistical threshold criteria method detected true positive results at target-to-background ratios much lower than the 1.5-to-1 target-to-background ratio of the 1.5-to-1 ratiometric threshold criteria method. CONCLUSIONS: The three-sigma statistical threshold criteria method was significantly better than the 1.5-to-1 ratiometric threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ detection of presumed abnormal (18)F-FDG-avid tissue sites during radioguided oncologic surgery. This finding may be extremely important for reshaping the ongoing and future research and development of gamma detection probe systems that are necessary for optimizing the in situ detection of radioisotopes of higher-energy gamma photon emissions used during radioguided oncologic surgery.

18F-FDG PET/CT oncologic imaging at extended injection-to-scan acquisition time intervals derived from a single-institution 18F-FDG-directed surgery experience: feasibility and quantification of 18F-FDG accumulation within 18F-FDG-avid lesions and background tissues.

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is a well-established imaging modality for a wide variety of solid malignancies. Currently, only limited data exists regarding the utility of PET/CT imaging at very extended injection-to-scan acquisition times. The current retrospective data analysis assessed the feasibility and quantification of diagnostic (18)F-FDG PET/CT oncologic imaging at extended injection-to-scan acquisition time intervals. METHODS: (18)F-FDG-avid lesions (not surgically manipulated or altered during (18)F-FDG-directed surgery, and visualized both on preoperative and postoperative (18)F-FDG PET/CT imaging) and corresponding background tissues were assessed for (18)F-FDG accumulation on same-day preoperative and postoperative (18)F-FDG PET/CT imaging. Multiple patient variables and (18)F-FDG-avid lesion variables were examined. RESULTS: For the 32 (18)F-FDG-avid lesions making up the final (18)F-FDG-avid lesion data set (from among 7 patients), the mean injection-to-scan times of the preoperative and postoperative (18)F-FDG PET/CT scans were 73 (± 3, 70-78) and 530 (± 79, 413-739) minutes, respectively (P < 0.001). The preoperative and postoperative mean (18)F-FDG-avid lesion SUV(max) values were 7.7 (± 4.0, 3.6-19.5) and 11.3 (± 6.0, 4.1-29.2), respectively (P < 0.001). The preoperative and postoperative mean background SUV(max) values were 2.3 (± 0.6, 1.0-3.2) and 2.1 (± 0.6, 1.0-3.3), respectively (P = 0.017). The preoperative and postoperative mean lesion-to-background SUV(max) ratios were 3.7 (± 2.3, 1.5-9.8) and 5.8 (± 3.6, 1.6-16.2), respectively, (P < 0.001). CONCLUSIONS: (18)F-FDG PET/CT oncologic imaging can be successfully performed at extended injection-to-scan acquisition time intervals of up to approximately 5 half-lives for (18)F-FDG while maintaining good/adequate diagnostic image quality. The resultant increase in the (18)F-FDG-avid lesion SUV(max) values, decreased background SUV(max) values, and increased lesion-to-background SUV(max) ratios seen from preoperative to postoperative (18)F-FDG PET/CT imaging have great potential for allowing for the integrated, real-time use of (18)F-FDG PET/CT imaging in conjunction with (18)F-FDG-directed interventional radiology biopsy and ablation procedures and (18)F-FDG-directed surgical procedures, as well as have far-reaching impact on potentially re-shaping future thinking regarding the "most optimal" injection-to-scan acquisition time interval for all routine diagnostic (18)F-FDG PET/CT oncologic imaging.

A Concept for Preoperative and Intraoperative Molecular Imaging and Detection for Assessing Extent of Disease of Solid Tumors.

The authors propose a concept of "systems engineering," the approach to assessing the extent of diseased tissue (EODT) in solid tumors. We modeled the proof of this concept based on our clinical experience with colorectal carcinoma (CRC) and gastrinoma that included short and long-term survival data of CRC patients. This concept, applicable to various solid tumors, combines resources from surgery, nuclear medicine, radiology, pathology, and oncology needed for preoperative and intraoperative assessments of a patient's EODT. The concept begins with a patient presenting with biopsy-proven cancer. An appropriate preferential locator (PL) is a molecule that preferentially binds to a cancer-related molecular target (i.e., tumor marker) lacking in non-malignant tissue and is the essential element. Detecting the PL after an intravenous injection requires the PL labeling with an appropriate tracer radionuclide, a fluoroprobe, or both. Preoperative imaging of the tracer's signal requires molecular imaging modalities alone or in combination with computerized tomography (CT). These include positron emission tomography (PET), PET/CT, single-photon emission computed tomography (SPECT), SPECT/CT for preoperative imaging, gamma cameras for intraoperative imaging, and gamma-detecting probes for precise localization. Similarly, fluorescent-labeled PLs require appropriate cameras and probes. This approach provides the surgeon with real-time information needed for R0 resection.

A multifaceted intervention to improve compliance with process measures for ICU clinician communication with ICU patients and families.

RATIONALE: Despite recommendations supporting the importance of clinician-family communication in the ICU, this communication is often rated as suboptimal in frequency and quality. We employed a multifaceted behavioral-change intervention to improve communication between families and clinicians in a statewide collaboration of ICUs. OBJECTIVES: Our primary objective was to examine whether the intervention resulted in increased compliance with process measures that targeted clinician-family communication. As secondary objectives, we examined the ICU-level characteristics that might be associated with increased compliance (open vs closed, teaching vs nonteaching, and medical vs medical-surgical vs surgical) and patient-specific outcomes (mortality, length of stay). METHODS: The intervention was a multifaceted quality improvement approach targeting process measures adapted from the Institute of Health Improvement and combined into two "bundles" to be completed either 24 or 72 hours after ICU admission. MEASUREMENTS AND MAIN RESULTS: Significant increases were seen in full compliance for both day 1 and day 3 process measures. Day 1 compliance improved from 10.7% to 83.8% after 21 months of intervention (p<0.001). Day 3 compliance improved from 1.6% to 28.8% (p<0.001). Improvements in compliance varied across ICU type with less improvement in open, nonteaching, and mixed medical-surgical ICUs. Patient-specific outcome measures were unchanged, although there was a small increase in patients discharged from ICU to inpatient hospice (p=0.002). CONCLUSIONS: We found that a multifaceted intervention in a statewide ICU collaborative improved compliance with specific process measures targeting communication with family members. The effect of the intervention varied by ICU type.

Site specific discrete PEGylation of (124)I-labeled mCC49 Fab' fragments improves tumor MicroPET/CT imaging in mice.

The tumor-associated glycoprotein-72 (TAG-72) antigen is highly overexpressed in various human adenocarcinomas and anti-TAG-72 monoclonal antibodies, and fragments are therefore useful as pharmaceutical targeting vectors. In this study, we investigated the effects of site-specific PEGylation with MW 2-4 kDa discrete, branched PEGylation reagents on mCC49 Fab' (MW 50 kDa) via in vitro TAG72 binding, and in vivo blood clearance kinetics, biodistribution, and mouse tumor microPET/CT imaging. mCC49Fab' (Fab'-NEM) was conjugated at a hinge region cysteine with maleimide-dPEG 12-(dPEG24COOH)3 acid (Mal-dPEG-A), maleimide-dPEG12-(dPEG12COOH)3 acid (Mal-dPEG-B), or maleimide-dPEG12-(m-dPEG24)3 (Mal-dPEG-C), and then radiolabeled with iodine-124 ((124)I) in vitro radioligand binding assays and in vivo studies used TAG-72 expressing LS174T human colon carcinoma cells and xenograft mouse tumors. Conjugation of mCC49Fab' with Mal-dPEG-A (Fab'-A) reduced the binding affinity of the non PEGylated Fab' by 30%; however, in vivo, Fab'-A significantly lengthened the blood retention vs Fab'-NEM (47.5 vs 28.1%/ID at 1 h, 25.1 vs 8.4%/ID at 5 h, p < 0.01), showed excellent tumor to background, better microPET/CT images due to higher tumor accumulation, and increased tumor concentration in excised tissues at 72 h by 130% (5.09 ± 0.83 vs 3.83 ± 1.50%ID/g, p < 0.05). Despite the strong similarity of the three PEGylation reagents, PEGylation with Mal-dPEG-B or -C reduced the in vitro binding affinity of Fab'-NEM by 70%, blood retention, microPET/CT imaging tumor signal intensity, and residual 72 h tumor concentration by 49% (3.83 ± 1.50 vs 1.97 ± 0.29%ID/g, p < 0.05) and 63% (3.83 ± 1.50 vs 1.42 ± 0.35%ID/g, p < 0.05), respectively. We conclude that remarkably subtle changes in the structure of the PEGylation reagent can create significantly altered biologic behavior. Further study is warranted of conjugates of the triple branched, negatively charged Mal-dPEG-A.

Intraoperative detection of ¹8F-FDG-avid tissue sites using the increased probe counting efficiency of the K-alpha probe design and variance-based statistical analysis with the three-sigma criteria.

BACKGROUND: Intraoperative detection of (18)F-FDG-avid tissue sites during 18F-FDG-directed surgery can be very challenging when utilizing gamma detection probes that rely on a fixed target-to-background (T/B) ratio (ratiometric threshold) for determination of probe positivity. The purpose of our study was to evaluate the counting efficiency and the success rate of in situ intraoperative detection of (18)F-FDG-avid tissue sites (using the three-sigma statistical threshold criteria method and the ratiometric threshold criteria method) for three different gamma detection probe systems. METHODS: Of 58 patients undergoing (18)F-FDG-directed surgery for known or suspected malignancy using gamma detection probes, we identified nine (18)F-FDG-avid tissue sites (from amongst seven patients) that were seen on same-day preoperative diagnostic PET/CT imaging, and for which each (18)F-FDG-avid tissue site underwent attempted in situ intraoperative detection concurrently using three gamma detection probe systems (K-alpha probe, and two commercially-available PET-probe systems), and then were subsequently surgical excised. RESULTS: The mean relative probe counting efficiency ratio was 6.9 (± 4.4, range 2.2-15.4) for the K-alpha probe, as compared to 1.5 (± 0.3, range 1.0-2.1) and 1.0 (± 0, range 1.0-1.0), respectively, for two commercially-available PET-probe systems (P < 0.001). Successful in situ intraoperative detection of 18F-FDG-avid tissue sites was more frequently accomplished with each of the three gamma detection probes tested by using the three-sigma statistical threshold criteria method than by using the ratiometric threshold criteria method, specifically with the three-sigma statistical threshold criteria method being significantly better than the ratiometric threshold criteria method for determining probe positivity for the K-alpha probe (P = 0.05). CONCLUSIONS: Our results suggest that the improved probe counting efficiency of the K-alpha probe design used in conjunction with the three-sigma statistical threshold criteria method can allow for improved detection of 18F-FDG-avid tissue sites when a low in situ T/B ratio is encountered.

Mathematical model of colitis-associated colon cancer.

As a result of chronic inflammation of their colon, patients with ulcerative colitis or Crohn's disease are at risk of developing colon cancer. In this paper, we consider the progression of colitis-associated colon cancer. Unlike normal colon mucosa, the inflammed colon mucosa undergoes genetic mutations, affecting, in particular, tumor suppressors TP53 and adenomatous polyposis coli (APC) gene. We develop a mathematical model that involves these genes, under chronic inflammation, as well as NF-κB, ß-catenin, MUC1 and MUC2. The model demonstrates that increased level of cells with TP53 mutations results in abnormal growth and proliferation of the epithelium; further increase in the epithelium proliferation results from additional APC mutations. The model may serve as a conceptual framework for further data-based study of the early stage of colon cancer.

Multimodal imaging and detection strategy with 124 I-labeled chimeric monoclonal antibody cG250 for accurate localization and confirmation of extent of disease during laparoscopic and open surgical resection of clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) accounts for approximately 85% to 90% of all primary kidney malignancies, with clear cell RCC (ccRCC) constituting approximately 70% to 85% of all RCCs. This study describes an innovative multimodal imaging and detection strategy that uses (124)I-labeled chimeric monoclonal antibody G250 ((124)I-cG250) for accurate preoperative and intraoperative localization and confirmation of extent of disease for both laparoscopic and open surgical resection of ccRCC. Two cases presented herein highlight how this technology can potentially guide complete surgical resection and confirm complete removal of all diseased tissues. This innovative (124)I-cG250 (ie, (124)I-girentuximab) multimodal imaging and detection approach, which would be clinically very useful to urologic surgeons, urologic medical oncologists, nuclear medicine physicians, radiologists, and pathologists who are involved in the care of ccRCC patients, holds great potential for improving the diagnostic accuracy, operative planning and approach, verification of disease resection, and monitoring for evidence of disease recurrence in ccRCC patients.

Disparities in Utilization of Palliative Care in Patients Experiencing Homelessness.

BACKGROUND: Patients experiencing homelessness have increased disease burden, increased severity of illness, and increased barriers to accessing care. The provision of high-quality palliative care is therefore essential for this population. State of Homelessness: 18 out of every 10,000 people in the US and 10 out of every 10,000 Rhode Islanders (down from 12 in 2010) experience homelessness. Conceptual Model: High-quality palliative care for patients experiencing homelessness requires a foundation of patient-provider trust, well-trained interdisciplinary teams, coordinated transitions of care, community support, integrated healthcare systems, and comprehensive population and public health measures. CONCLUSIONS: Improving access to palliative care for those experiencing homelessness requires an interdisciplinary approach at all levels from individual providers to broader public health policies. A conceptual model rooted in patient-provider trust has the potential to address high-quality palliative care access disparities for this vulnerable population.

Repeat hepatectomy for metastatic colorectal cancer is safe but marginally effective.

BACKGROUND: Although hepatectomy for metastatic colorectal cancer (mCRC) offers prolonged survival in up to 40% of people, recurrence rates are high, approaching 70%. Many patients experience recurrent disease in the liver after initial hepatectomy. We examined our experience with repeat hepatectomy for mCRC. METHODS: After Institutional Review Board approval, we reviewed the records of all patients at a single institution who underwent hepatectomy for mCRC. Repeat hepatectomy was defined as partial liver resection any time after the initial hepatectomy for recurrent mCRC. We estimated time to recurrence and survival by using the Kaplan-Meier method and compared outcomes between groups by using the log-rank test. RESULTS: From 1998 to 2008, 405 patients underwent hepatectomy for mCRC, and 215 (53%) experienced disease recurrence at a median of 13 months. Of 150 patients with liver-only or liver-predominant recurrence, 52 (35%) underwent repeat hepatectomy. The median time to recurrence after repeat hepatectomy was 10 months, and median overall survival was 19 months. There was one (1.9%) perioperative death, and there were 14 (27%) major complications. The median overall survival in the repeat hepatectomy group from the time of recurrence after initial hepatectomy was 22 months, compared with 15 months in the 98 patients with liver recurrence who were not selected for repeat hepatectomy (P=0.02). CONCLUSIONS: Repeat hepatectomy for mCRC is feasible in highly selected patients, with acceptable perioperative morbidity and mortality. Although repeat hepatectomy should be considered, recurrence rates are high. Although the initial hepatectomy for mCRC is potentially curative, recurrence of metastatic disease in the liver is unlikely to be cured.