Non-spouse companions accompanying older adults to medical visits: a qualitative analysis.

BACKGROUND: Medical Visit Companions (MVCs) are encouraged for older adults' routine medical encounters. Little data exist on the experiences and contributions of non-spouse companions for the growing population of older adults without a living spouse. METHODS: We conducted six focus groups with forty non-spouse MVCs identified through churches in Baltimore, Maryland. Thematic analysis was used to identify key issues before the visit, during the visit itself, after the visit, and in the overall companion experience. RESULTS: MVCs described their experiences positively but also highlighted many challenges related to the role that extended far beyond the visit itself. These included scheduling, transportation, communication, and coordination of care expectations. CONCLUSION: Our increasingly complex healthcare system can be challenging for older adults to navigate successfully. The diverse nature of tasks performed by companions in this study highlight the many benefits of having a companion accompany older patients to medical visits. The positive experience of the companions studied and their willingness to continue their role in the future highlights the untapped potential for increased social facilitation to improve the quality of healthcare visits and achieve patient-centered care for all older patients.

Momentum-exchange interactions in a Bragg atom interferometer suppress Doppler dephasing.

Large ensembles of laser-cooled atoms interacting through infinite-range photon-mediated interactions are powerful platforms for quantum simulation and sensing. Here we realize momentum-exchange interactions in which pairs of atoms exchange their momentum states by collective emission and absorption of photons from a common cavity mode, a process equivalent to a spin-exchange or XX collective Heisenberg interaction. The momentum-exchange interaction leads to an observed all-to-all Ising-like interaction in a matter-wave interferometer. A many-body energy gap also emerges, effectively binding interferometer matter-wave packets together to suppress Doppler dephasing in analogy to Mössbauer spectroscopy. The tunable momentum-exchange interaction expands the capabilities of quantum interaction-enhanced matter-wave interferometry and may enable the realization of exotic behaviors, including simulations of superconductors and dynamical gauge fields.

Genomic analyses of hair from Ludwig van Beethoven.

Ludwig van Beethoven (1770-1827) remains among the most influential and popular classical music composers. Health problems significantly impacted his career as a composer and pianist, including progressive hearing loss, recurring gastrointestinal complaints, and liver disease. In 1802, Beethoven requested that following his death, his disease be described and made public. Medical biographers have since proposed numerous hypotheses, including many substantially heritable conditions. Here we attempt a genomic analysis of Beethoven in order to elucidate potential underlying genetic and infectious causes of his illnesses. We incorporated improvements in ancient DNA methods into existing protocols for ancient hair samples, enabling the sequencing of high-coverage genomes from small quantities of historical hair. We analyzed eight independently sourced locks of hair attributed to Beethoven, five of which originated from a single European male. We deemed these matching samples to be almost certainly authentic and sequenced Beethoven's genome to 24-fold genomic coverage. Although we could not identify a genetic explanation for Beethoven's hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease. Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven's severe liver disease, which culminated in his death. Unexpectedly, an analysis of Y chromosomes sequenced from five living members of the Van Beethoven patrilineage revealed the occurrence of an extra-pair paternity event in Ludwig van Beethoven's patrilineal ancestry.

Metallofullerene-nanoplatform-delivered interstitial brachytherapy improved survival in a murine model of glioblastoma multiforme.

Fullerenes are used across scientific disciplines because of their diverse properties gained by altering encapsulated or surface-bound components. In this study, the recently developed theranostic agent based on a radiolabeled functionalized metallofullerene ((177)Lu-DOTA-f-Gd(3)N@C(80)) was synthesized with high radiochemical yield and purity. The efficacy of this agent was demonstrated in two orthotopic xenograft brain tumor models of glioblastoma multiforme (GBM). A dose-dependent improvement in survival was also shown. The in vivo stability of the agent was verified through dual label measurements of biological elimination from the tumor. Overall, these results provide evidence that nanomaterial platforms can be used to deliver effective interstitial brachytherapy.

Metallofullerene-based nanoplatform for brain tumor brachytherapy and longitudinal imaging in a murine orthotopic xenograft model.

PURPOSE: To demonstrate in an orthotopic xenograft brain tumor model that a functionalized metallofullerene (f-Gd3N@C80) can enable longitudinal tumor imaging and, when radiolabeled with lutetium 177 (¹77Lu) and tetraazacyclododecane tetraacetic acid (DOTA) (¹77Lu-DOTA-f-Gd3N@C80), provide an anchor to deliver effective brachytherapy. MATERIALS AND METHODS: All experiments involving the use of mice were carried out in accordance with protocols approved by the institutional animal care and use committee. Human glioblastoma U87MG cells were implanted by using stereotactic procedures into the brains of 37 female athymic nude-Foxn1nu mice and allowed to develop into a tumor for 8 days. T1- and T2-weighted magnetic resonance (MR) imaging was performed in five mice. Biodistribution studies were performed in 12 mice at four time points over 7 days to evaluate gadolinium content. Survival studies involved 20 mice that received infusion of a nanoplatform by means of convection-enhanced delivery (CED) 8 days after tumor implantation. Mice in survival studies were divided into two groups: one comprised untreated mice that received f-Gd3N@CC80 alone and the other comprised mice treated with brachytherapy that received 1.11 MBq of ¹77Lu-DOTA-f-Gd3N@CC80. Survival data were evaluated by using Kaplan-Meier statistical methods. RESULTS: MR imaging showed extended tumor retention (25.6% ± 1.2 of the infused dose at 52 days, confirmed with biodistribution studies) of the f-Gd3N@CC80 nanoplatform, which enabled longitudinal imaging. Successful coupling of ¹77Lu to the f-Gd3N@CC80 surface was achieved by using a bifunctional macrocyclic chelator. The extended tumor retention allowed for effective brachytherapy, as indicated by extended survival time (> 2.5 times that of the untreated group) and histologic signs of radiation-induced tumor damage. CONCLUSION: The authors have developed a multimodal nanoplatform and have demonstrated longitudinal tumor imaging, prolonged intratumoral probe retention, biodistribution, and extended survival in an orthotopic xenograft brain tumor model.

Encapsulation of a radiolabeled cluster inside a fullerene cage, (177)Lu(x)Lu((3-x))N@C(80): an interleukin-13-conjugated radiolabeled metallofullerene platform.

In this communication, we describe the successful encapsulation of (177)Lu into the endohedral metallofullerene (177)Lu(x)Lu(3-x)N@C(80) (x = 1-3) starting with (177)LuCl(3) in a modified quartz Kraschmer-Huffman electric generator. We demonstrate that the (177)Lu (beta-emitter) in this fullerene cage is not significantly released for a period of up to at least one-half-life (6.7 days). We also demonstrate that this agent can be conjugated with an interleukin-13 peptide that is designed to target an overexpressed receptor in glioblastoma multiforme tumors. This nanoparticle delivery platform provides flexibility for a wide range of radiotherapeutic and radiodiagnostic multimodal applications.

The effect of biofuel production on swine farm methane and ammonia emissions.

Methane (CH) and ammonia (NH3) are emitted to the atmosphere during anaerobic processing of organic matter, and both gases have detrimental environmental effects. Methane conversion to biofuel production has been suggested to reduce CH4 emissions from animal manure processing systems. The purpose of this research is to evaluate the change in CH4 and NH3 emissions in an animal feeding operation due to biofuel production from the animal manure. Gas emissions were measured from swine farms differing only in their manure-management treatment systems (conventional vs. biofuel). By removing organic matter (i.e., carbon) from the biofuel farms' manure-processing lagoons, average annual CH4 emissions were decreased by 47% compared with the conventional farm. This represents a net 44% decrease in global warming potential (CO2 equivalent) by gases emitted from the biofuel farms compared with conventional farms. However, because of the reduction of methanogenesis and its reduced effect on the chemical conversion of ammonium (NH4+) to dinitrogen (N2) gas, NH3 emissions in the biofuel farms increased by 46% over the conventional farms. These studies show that what is considered an environmentally friendly technology had mixed results and that all components of a system should be studied when making changes to existing systems.

Imaging multidrug resistance with 4-[18F]fluoropaclitaxel.

Multidrug resistance (MDR) is a cause of treatment failure in many cancer patients. MDR refers to a phenotype whereby a tumor is resistant to a large number of natural chemotherapeutic drugs. Having prior knowledge of the presence of such resistance would decrease morbidity from unsuccessful therapy and allow for the selection of individuals who may benefit from the coadministration of MDR-inhibiting drugs. The Tc-99m-labeled single-photon-emitting radiotracers sestamibi and tetrofosmin have shown some predictive value. However, positron-emitting radiotracers, which allow for dynamic quantitative imaging, hold promise for a more accurate and specific identification of MDRtumors.MDR-expressing tumors are resistant to paclitaxel, which is commonly used as a chemotherapeutic agent. 4-[18F]Fluoropaclitaxel (FPAC) is a PET-radiolabeled analogue of paclitaxel. Preclinical studies have shown the uptake of FPAC to be inversely proportional to tumor MDR expression. FPAC PET imaging in normal volunteers shows biodistribution to be similar to that in nonhuman primates. Imaging in a breast cancer patient showed FPAC localization in a primary tumor that responded to chemotherapy, while failure to localize in mediastinal disease corresponded with only partial response.FPAC PET imaging shows promise for the noninvasive pretreatment identification of MDR-expressing tumors. While much additional work is needed, this work represents a step toward image-guided personalized medicine.

Physician knowledge of nuclear medicine radiation exposure.

PURPOSE: Because physician knowledge of patient exposure to ionizing radiation from computed tomography (CT) procedures previously has been recognized as poor, the purpose of this systematic review is to determine whether physician or physician trainee knowledge of patient exposure to radiation from nuclear medicine procedures is similarly insufficient. METHODS: Online databases and printed literature were systematically searched to acquire peer-reviewed published research studies involving assessment of physician or physician trainee knowledge of patient radiation exposure levels incurred during nuclear medicine and CT procedures. An a priori inclusion/exclusion criteria for study selection was used as a review protocol aimed at extracting information pertaining to participants, collection methods, comparisons within studies, outcomes, and study design. RESULTS: Fourteen studies from 8 countries were accepted into the review and revealed similar insufficiencies in physician knowledge of nuclear medicine and CT patient radiation exposures. Radiation exposure estimates for both modalities similarly featured a strong tendency toward physician underestimation. Discussion Comparisons were made and ratios established between physican estimates of patient radiation exposure from nuclear medicine procedures and estimates of CT procedures. A theoretical median of correct physician exposure estimates was used to examine factors affecting lower and higher estimates. CONCLUSION: The tendency for ordering physicians to underestimate patient radiation exposures from nuclear medicine and CT procedures could lead to their overuse and contribute to increasing the public's exposure to ionizing radiation.

Human dosimetry and preliminary tumor distribution of 18F-fluoropaclitaxel in healthy volunteers and newly diagnosed breast cancer patients using PET/CT.

UNLABELLED: (18)F-fluoropaclitaxel is a radiolabeled form of paclitaxel, a widely used chemotherapy agent. Preclinical data suggest that (18)F-fluoropaclitaxel may be a reasonable surrogate for measuring the uptake of paclitaxel. As a substrate of P-glycoprotein, a drug efflux pump associated with multidrug resistance, (18)F-fluoropaclitaxel may also be useful in identifying multidrug resistance and predicting tumor response for drugs other than paclitaxel. METHODS: After informed consent was obtained, 3 healthy volunteers and 3 patients with untreated breast cancer (neoadjuvant chemotherapy candidates, tumor size > 2 cm) received an intravenous infusion of (18)F-fluoropaclitaxel and then underwent PET/CT. Healthy volunteers underwent serial whole-body imaging over an approximately 3-h interval, and organ (18)F residence times were determined from the time-activity curves uncorrected for decay to determine dosimetry. Radiation dose estimates were calculated using OLINDA/EXM software. For breast cancer patients, dynamic imaging of the primary tumor was performed for 60 min, followed by static whole-body scans at 1 and 2 h after injection. RESULTS: Dosimetry calculations showed that the gallbladder received the highest dose (229.50 µGy/MBq [0.849 rad/mCi]), followed by the small and large intestines (161.26 µGy/MBq [0.597 rad/mCi] and 184.59 µGy/MBq [0.683 rad/mCi]). The resultant effective dose was 28.79 µGy/MBq (0.107 rem/mCi). At approximately 1 h after injection, an average of 42% of the decay-corrected activity was in the gastrointestinal system, with a mean of 0.01% in the tumor. All 3 breast cancer patients showed retention of (18)F-fluoropaclitaxel and ultimately demonstrated a complete pathologic response (no invasive cancer in the breast or axillary nodes) to chemotherapy that included a taxane (either paclitaxel or docetaxel) at surgical resection. The tumor-to-background ratio increased with time to a maximum of 7.7 at 20 min. CONCLUSION: This study demonstrates the feasibility of using (18)F-fluoropaclitaxel PET/CT tumor imaging and provides radiation dosimetry measurements in humans. Although further study is needed, it is hoped that the measured intratumoral (18)F-fluoropaclitaxel distribution can serve as a surrogate for paclitaxel, and potentially other chemotherapeutic agent retention, in solid tumors.

Underestimation of the presence of breast carcinoma in papillary lesions initially diagnosed at core-needle biopsy.

PURPOSE: To retrospectively determine the degree of underestimation of breast carcinoma diagnosis in papillary lesions initially diagnosed at core-needle biopsy. MATERIALS AND METHODS: Institutional review board approval and waiver of informed consent were obtained for this HIPAA-compliant study. Mammographic database review (1994-2003) revealed core biopsy diagnoses of benign papilloma (n=38), atypical papilloma (n=15), sclerotic papilloma (n=6), and micropapilloma (n=4) in 57 women (mean age, 57 years). Excisional or mammographic follow-up (>or=2 years) findings were available. Patients with in situ or invasive cancer in the same breast or patients without follow-up were excluded. Findings were collected from mammography, ultrasonography, core technique, core biopsy, excision, and subsequent mammography. Reference standard was excisional findings or follow-up mammogram with no change at 2 years. Associations were examined with regression methods. RESULTS: In 38 of 63 lesions, surgical excision was performed; in 25 additional lesions (considered benign), follow-up mammography (24-month minimum) was performed, with no interval change. In 15 lesions, 14-gauge core needle was used; in 48, vacuum assistance (mean cores per lesion, 8.7). Carcinoma was found at excision in 14 of 38 lesions. Core pathologic findings associated with malignancy were benign papilloma (n=1), sclerotic papilloma (n=1), micropapilloma (n=2), and atypical papilloma (n=10). Frequency of malignancy was one (3%) of 38 benign papillomas, 10 (67%) of 15 atypical papillomas, two (50%) of four micropapillomas, and one (17%) of six sclerotic papillomas. Excisional findings included lobular carcinoma in situ (n=2), ductal carcinoma in situ (n=7), papillary carcinoma (n=2), and invasive ductal carcinoma (n=3). Low-risk group (micropapillomas and sclerotic and benign papillomas) was compared with high-risk atypical papilloma group. Core findings were associated with malignancy at excision for atypical papilloma (P=.006). Lesion location, mammographic finding, core number, or needle type were not associated (P>.05) with underestimation of malignancy at excision. CONCLUSION: Benign papilloma diagnosed at core biopsy is infrequently (3%) associated with malignancy; mammographic follow-up is reasonable. Because of the high association with malignancy (67%), diagnosis of atypical papilloma at core biopsy should prompt excision for definitive diagnosis.

An orexigenic role for mu-opioid receptors in the lateral parabrachial nucleus.

The pontine parabrachial nucleus (PBN) has been implicated in regulating ingestion and contains opioids that promote feeding elsewhere in the brain. We tested the actions of the selective mu-opioid receptor (mu-OR) agonist [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) in the PBN on feeding in male rats with free access to food. Infusing DAMGO (0.5-4.0 nmol/0.5 microl) into the lateral parabrachial region (LPBN) increased food intake. The hyperphagic effect was anatomically specific to infusions within the LPBN, dose and time related, and selective for ingestion of chow compared with (nonnutritive) kaolin. The nonselective opioid antagonist naloxone (0.1-10.0 nmol intra-PBN) antagonized DAMGO-induced feeding, with complete blockade by 1.0 nmol and no effect on baseline. The highly selective mu-opioid antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; 1.0 nmol) also prevented this action of DAMGO, but the kappa-antagonist nor-binaltorphimine did not. Naloxone and CTAP (10.0 nmol) decreased intake during scheduled feeding. Thus stimulating mu-ORs in the LPBN increases feeding, whereas antagonizing these sites inhibits feeding. Together, our results implicate mu-ORs in the LPBN in the normal regulation of food intake.

Focal asymmetric densities seen at mammography: US and pathologic correlation.

The American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) defines four different types of asymmetric breast findings: asymmetric breast tissue, densities seen in one projection, architectural distortion, and focal asymmetric densities. These lesions are frequently encountered at screening and diagnostic mammography and are significant because they may indicate a neoplasm, especially if an associated palpable mass is present. Once these lesions are detected at standard mammography, supplementary breast imaging with additional mammographic views and ultrasonography (US) can be a key aspect of work-up. The role of US in this setting has not been clearly defined. However, a positive US finding such as a solid mass or an area of focal shadowing increases the level of suspicion for malignancy. A thorough knowledge of the patient's clinical history, along with a fundamental understanding of the ACR BI-RADS lexicon and the role and limitations of supplementary breast imaging, will allow more accurate interpretation of these potentially perplexing soft-tissue findings.

Comparison of the computer programs DEREK and TOPKAT to predict bacterial mutagenicity. Deductive Estimate of Risk from Existing Knowledge. Toxicity Prediction by Komputer Assisted Technology.

The performance of two computer programs, DEREK and TOPKAT, was examined with regard to predicting the outcome of the Ames bacterial mutagenicity assay. The results of over 400 Ames tests conducted at Glaxo Wellcome (now GlaxoSmithKline) during the last 15 years on a wide variety of chemical classes were compared with the mutagenicity predictions of both computer programs. DEREK was considered concordant with the Ames assay if (i) the Ames assay was negative (not mutagenic) and no structural alerts for mutagenicity were identified or (ii) the Ames assay was positive (mutagenic) and at least one structural alert was identified. Conversely, the DEREK output was considered discordant if (i) the Ames assay was negative and any structural alert was identified or (ii) the Ames assay was positive and no structural alert was identified. The overall concordance of the DEREK program with the Ames results was 65% and the overall discordance was 35%, based on over 400 compounds. About 23% of the test molecules were outside the permissible limits of the optimum prediction space of TOPKAT. Another 4% of the compounds were either not processable or had indeterminate mutagenicity predictions; these molecules were excluded from the TOPKAT analysis. If the TOPKAT probability was (i) > or =0.7 the molecule was predicted to be mutagenic, (ii) < or =0.3 the compound was predicted to be non-mutagenic and (iii) between 0.3 and 0.7 the prediction was considered indeterminate. From over 300 acceptable predictions, the overall TOPKAT concordance was 73% and the overall discordance was 27%. While the overall concordance of the TOPKAT program was higher than DEREK, TOPKAT fared more poorly than DEREK in the critical Ames-positive category, where 60% of the compounds were incorrectly predicted by TOPKAT as negative but were mutagenic in the Ames test. For DEREK, 54% of the Ames-positive molecules had no structural alerts and were predicted to be non-mutagenic. Alternative methods of analyzing the output of the programs to increase the accuracy with Ames-positive compounds are discussed.