Adolescent alcohol exposure produces sex differences in negative affect-like behavior and group I mGluR BNST plasticity.

Adolescent alcohol exposure increases the risk of developing alcohol use disorders (AUDs), yet the mechanisms responsible for this vulnerability remain largely unknown. One potential target for alcohol-induced changes is the circuitry that modulates negative affect and stress, two sexually dependent drivers of alcohol relapse. The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic region that critically regulates negative affective- and stress-induced relapse. Group I metabotropic glutamate receptors (mGluR) are a target of interest due to their regulation of stress, anxiety behaviors, and BNST plasticity. The current studies investigate sex-dependent sensitivity to the effects of adolescent intermittent ethanol vapor exposure (AIE) on negative affect during acute and protracted alcohol withdrawal and following stress in adulthood. This work also assessed whether BNST group I mGluR-mediated long-term depression (LTD) was disrupted at these timepoints. During acute withdrawal, AIE altered LTD induced by the group I mGluR antagonist DHPG in females, but not males. During adulthood, stress unmasked persistent changes in DHPG-induced LTD and behavior that were not present under basal conditions. Females with an AIE history demonstrated enhanced negative affective-like behavior in the novelty-induced hypophagia test following restraint stress-a phenotype that could be blocked with systemic mGluR5 allosteric antagonism via MTEP. Conversely, males with an AIE history demonstrated elevated freezing in a contextual fear conditioning paradigm. These studies demonstrate long-lasting, sex-dependent phenotypes produced by AIE and suggest pharmaceutical interventions for alcohol use and comorbid disorders may be more effective if designed with sex differences in mind.

A simple foot pedal device in a horizontal bore imaging facility replicates weightbearing outcomes for Hallux Valgus patients.

BACKGROUND: Weightbearing images are important to the diagnosis of foot pathologies as are the three dimensional views available from CT and MRI. Standard three-dimensional imaging hardware, however, does not have a simple tool to obtain weightbearing images. The current research aimed to design, build and test a simple device to apply load in a horizontal bore imaging facility. METHODS: With the immediate need in hallux valgus studies, hallux valgus subjects were imaged using the new loading device, which could be easily transported and had no additional electronics. RESULTS: Testing showed that the usual angular measures of the foot (intermetatarsal and hallux valgus) replicated the results from the standard of care standing plain film results. With application of load, HV angle changed from 29.9° non-weightbearing to 32.2° weightbearing, while IM angle changed from nonweightbearing 15.8° to weightbearing 16.5°. CONCLUSION: The pedal-like device can provide weightbearing images in a horizontal bore MRI facility.

Weight-bearing recommendations after first metatarsophalangeal joint arthrodesis fixation: a biomechanical comparison.

BACKGROUND: This study sought to determine whether several metatarsophalangeal (MTP) fusion techniques require complete immobilization or if some level of weight-bearing could be recommended after surgery. A comparison of synthetic composite to actual bone was included in order to examine the validity of the testing conditions. METHODS: Four MTP fusion modalities were tested in synthetic composite bone models: unlocked plating, locked plating, crossed lag screws, and an unlocked plate with a single lag screw. Stiffness was calculated and then used to find the two most rigid constructs; the load to failure was recorded. Stiffness and load to failure testing for the two more rigid constructs in paired cadaveric bones were followed. RESULTS: The unlocked plate plus screw and crossed screw constructs were stiffest (p < 0.008). Loads to failure of the unlocked plate plus screw and crossed screws in synthetic bone were 131 and 101 N, respectively and in cadaveric bone were 154 and 94 N, respectively, which are less than the estimated 25% body weight required at the MTP joint. The plate plus screws were statistically more stiff than crossed screws (p = 0.008), but there was no statistical difference between synthetic and cadaveric bone in load to failure (p = 0.296). CONCLUSIONS: The plate plus screw offered the greatest stiffness; the failure test showed that no construct could withstand weight-bearing as tolerated; and, synthetic composite models of the MTP joint did not provide the consistent results in stiffness and failure.

Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

BACKGROUND: Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. PATIENTS AND METHODS: Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). RESULTS: Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P < 0.001) and grade ≥3 (9% versus 2%, P < 0.001) was significantly lower in arm B, independent of the platinum drug used. The median final paclitaxel dose was significantly lower in arm B (199 versus 150 mg/m(2), P < 0.001). Response rate was similar in arms A and B (31% versus 27%, P = 0.405), as was adjusted median PFS [5.5 versus 4.9 months, hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.49, P = 0.228] and OS (10.1 versus 9.5 months, HR 1.05, 95% CI 0.81-1.37, P = 0.682). CONCLUSION: PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. CLINICAL TRIAL INFORMATION: NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767).

Effect of forage type with or without corn supplementation on animal performance, beef fatty acid composition, and palatability.

Thirty-two steers were used to examine forage type (legumes [ and ] vs. grasses [ and ]) with or without individual corn grain supplementation (0 vs. 0.75% of live weight [LW]/d) on beef fatty acid composition and palatability. In each year, steers ( = 16/yr) were randomly assigned to forage type ( = 8/forage type per yr) and to supplementation treatments within forage type ( = 4/supplementation treatment/forage type per yr). Forage types (grasses vs. legumes) were replicated in 2 paddocks of perennial and annual forage type pastures. A mixed model was developed with forage type, corn grain supplementation, and the 2-way interaction as fixed effects and 2 different error terms, one for testing forage and another for testing grain supplement and grain supplement × forage interaction. Corn grain supplementation increased ( = 0.01) ADG by 0.29 kg/d and final LW by 13 kg. Hot carcass weight, dressing percentage (DP), and KPH were greater ( < 0.05) for steers supplemented with corn grain. Carcasses from steers grazing legumes had greater ( = 0.04) DP compared with carcasses from steers grazing grasses. Alpha-linolenic acid concentration was higher ( < 0.05) in LM of steers grazing legumes than in LM of steers grazing grasses, both without supplementation. Supplementation decreased ( < 0.05) linolenic acid levels for both forage types; however, the magnitude of this reduction was greater for legumes than for grasses. The ratio of -6 to -3 PUFA was greater ( = 0.03) in the LM of corn grain-supplemented steers than in the LM of nonsupplemented steers. Supplementation of corn grain decreased ( < 0.05) the percentage of odd-chain fatty acids and increased ( < 0.05) the percentage of MUFA in the LM. Warner-Bratzler shear force values were not altered ( > 0.05) by forage type, supplementation, or the 2-way interaction. Beef finished on legumes had greater concentrations of -3 PUFA, whereas beef supplemented with corn grain had a greater ratio of -6 to -3 fatty acids. On a gravimetric basis (mg/100 g LM), -3 PUFA and CLA contents were not altered with supplementation, indicating that corn grain can be supplemented at this level in a forage-finishing beef system without negative consequences on perceived beneficial fatty acids.

Effect of frame size and time-on-pasture on steer performance, longissimus muscle fatty acid composition, and tenderness in a forage-finishing system.

Angus-cross steers (n = 96; BW = 309 ± 34 kg; 13.5 mo of age) were used to determine the effects of frame size (medium or small) and time-on-pasture (TOP) on meat composition and palatability in a 2-yr study. Finishing steers grazed mixed pastures (bluegrass/white clover; April start) and were slaughtered after 89-, 146-, and 201-d TOP. At 24 h postmortem, carcass traits were collected and a rib from each carcass was obtained for proximate and fatty acid composition, Warner-Bratzler shear force (WBSF), and postmortem proteolysis. In yr 1, postmortem aging treatments included 14 and 28 d, whereas in yr 2, postmortem aging treatments included 2, 4, 7, 14, and 28 d. Increasing frame size of the finishing steers produced greater (P < 0.05) ADG by 0.10 kg, BW by 24 kg, HCW by 14 kg, and ribeye size by 2.65 cm(2). All other carcass, meat composition, and tenderness measures did not differ (P > 0.05) due to frame size or 2-way interaction with TOP. Increasing TOP resulted in quadratic increases (P < 0.01) in BW and HCW. Ribeye area, fat thickness, KPH, marbling scores, quality grades, and yield grades increased (P < 0.001) linearly as TOP increased. Time-on-pasture linearly increased (P = 0.001) palmitic (C16:0) acid, oleic (C18:1 cis-9) acid, SFA, and MUFA in the LM. Both n-6 PUFA, linoleic (C18:2) and arachidonic (C20:4) acids, decreased linearly (P = 0.001) with increasing TOP. Increasing TOP linearly reduced (P = 0.01) concentrations of all n-3 fatty acids in the LM. These changes resulted in a linear reduction (P = 0.01) in n-6 to n-3 fatty acid ratio with advancing TOP; however, the magnitude of the difference was small (1.46 vs. 1.37). At 14 d of postmortem aging, WBSF was lowest (P < 0.001) for 89-d TOP and greatest (P < 0.05) for the 201-d TOP. After 28 d of postmortem aging, WBSF values for 89- and 146-d TOP did not differ (P > 0.05) compared to the 14-d postmortem aging WBSF values. However, in steaks from 201-d TOP, additional postmortem aging to 28 d reduced (P < 0.001) WBSF. In pasture-based beef finishing systems, increasing TOP increases animal age, HCW, fat thickness, and marbling score; however, tenderness of ribeye steaks decreased with advanced TOP such that longer postmortem aging times were required to achieve similar tenderness levels.

Effect of summer forage species grazed during finishing on animal performance, carcass quality, and meat quality.

Angus-cross steers (n = 60) were used to assess the effect of forage species [alfalfa (AL; Medicago sativa L.), bermudagrass (BG; Cynodon dactylon), chicory (CH; Cichorium intybus L.), cowpea (CO; Vigna unguiculata L.), and pearl millet (PM; Pennisetum glaucum (L. R Br.)] in replicated 2-ha paddocks for finishing on cattle performance, carcass quality, and meat quality in a 2-yr study. Steers were blocked by BW and assigned randomly to finishing-forage treatments before the start of the experiment. Steers grazing AL and CH had greater (P < 0.05) ADG than those grazing for BG, CO, and PM, whereas AL produced more (P < 0.05) gain/ha than CH, CO, and PM. Days steers spent grazing were longest (P < 0.05) for PM and shortest (P < 0.05) for CO. Steers grazing BG and CO produced heavier (P < 0.05) HCW than steers grazing BG and PM. Dressing percentage was greatest (P < 0.05) in steers grazing CO, and grazing AL resulted in greater (P < 0.05) dressing percentages than grazing BG, CH, and PM. Grazing AL and CH produced carcasses with more (P < 0.05) fat at the 12th rib than steers grazing warm-season grasses (BG and PM). Marbling scores tended to be greater (P = 0.06) for CO, but carcasses from steers grazing CO received greater (P < 0.05) quality grades than AL and CH. Trans-11 vaccenic (C18:1 trans-11; TVA) acid concentration in the LM was greater (P < 0.05) for BG than CH, CO, and AL. Conjugated linoleic acid, cis-9 trans-11 isomer, concentration was greatest (P < 0.05) for BG and PM than AL, CH, and CO. Grazing CH and PM increased (P < 0.05) the ratio of omega-6 to omega-3 fatty acids in the LM compared with AL, BG, and CO. Grazing legumes (AL and CO) resulted in lower (P < 0.05) Warner-Bratzler shear force values than other forage species. Consumers rated steaks from steers finished on AL and CO pastures greatest (P < 0.05) and steaks from steers finished on BG and CH least (P < 0.05) for overall palatability. Consumer preference was greatest (P < 0.05) for steaks from steers finished on AL and least (P < 0.05) for steaks from steers finished on BG and CH. Finishing steers on AL and CH during summer increased steer performance (> 1 kg/d). Finishing on legumes (AL and CO) increased dressing percentage, reduced Warner-Bratzler shear force values, and increased consumers preference, whereas finishing on grasses (BG and PM) enhanced anticarcinogenic fatty acid concentrations.

Cis-9, trans-11 conjugated linoleic acid is endogenously synthesized from palmitelaidic (C16:1 trans-9) acid in bovine adipocytes.

Palmitelaidic (C16:1 trans-9) acid has been suggested to have beneficial effects on human health, including reduced adiposity. Objectives of this research were to quantify the amounts of palmitelaidic acid in beef samples and determine the effect of palmitelaidic acid supplementation on lipogenesis in bovine preadipocytes and adipocytes in vitro. For the first objective, palmitelaidic acid content of LM samples from steers finished on forage or concentrate systems was determined. Palmitelaidic acid in LM samples from forage-finished beef ranged from 10 to 17 mg/100 g of muscle corresponding to 0.52% to 0.65% of total fatty acids. Forage species grazed during finishing, and animal age at harvest also altered palmitelaidic acid concentrations and contents in the LM of forage-finished beef. Palmitelaidic acid concentration of concentrate-finished beef was lower (P < 0.05; 0.25% vs. 0.56%); however, because of increased (P < 0.05) total fatty acid content with concentrate finishing, amount of palmitelaidic acid was similar (P > 0.05) to beef from steers finished on pearl millet and greater (P < 0.05) than those finished on alfalfa. For the second objective, undifferentiated preadipocytes and differentiated adipocytes were supplemented with 0 to 300 µM of palmitelaidic acid. Palmitelaidic acid supplementation reduced (P < 0.05) cell viability of undifferentiated preadipocytes at greater levels (150 and 300 µM) but did not affect (P > 0.05) the viability of differentiated adipocytes. In preadipocytes, palmitelaidic acid increased (P < 0.05) palmitelaidic and trans-11 vaccenic (C18:1 trans-11) acids at high levels of supplementation (300 µM). In adipocytes, palmitelaidic acid supplementation increased (P < 0.05) palmitelaidic acid, trans-11 vaccenic acid, and total fatty acid content. In addition, cis-9, trans-11 CLA also increased (P < 0.05) with palmitelaidic acid supplementation in adipocytes. These results indicate that palmitelaidic acid can be elongated in both preadipocytes and adipocytes and desaturated in adipocytes to generate trans-11 vaccenic acid and cis-9, trans-11 CLA, respectively. Beef products are a source of palmitelaidic acid in the human diet, which can be elongated and desaturated to produce trans-11 vaccenic acid and cis-9, trans-11 CLA.

Relationship among circulating tumor cells, CEA and overall survival in patients with metastatic colorectal cancer.

BACKGROUND: We previously reported results of a prospective trial evaluating the significance of circulating tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). This secondary analysis assessed the relationship of the CTC number with carcinoembryonic antigen (CEA) and overall survival. PATIENTS AND METHODS: Patients with mCRC had CTCs measured at baseline and specific time points after the initiation of new therapy. Patients with a baseline CEA value ≥ 10 ng/ml and CEA measurements within ± 30 days of the CTC collection were included. RESULTS: We included 217 patients with mCRC who had a CEA value of ≥ 10 ng/ml. Increased baseline CEA was associated with shorter survival (15.8 versus 20.7 months, P = 0.012). Among all patients with a baseline CEA value of ≥ 25 ng/ml, patients with low baseline CTCs (<3, n = 99) had longer survival than those with high CTCs (≥ 3, n = 58; 20.8 versus 11.7 months, P = 0.001). CTCs added prognostic information at the 3-5- and 6-12-week time points regardless of CEA. In a multivariate analysis, CTCs at baseline but not CEA independently predicted survival and both CTCs and CEA independently predicted survival at 6-12 weeks. CONCLUSIONS: This study demonstrates that both CEA and CTCs contribute prognostic information for patients with mCRC.

Design and implementation of a multichannel millimeter wave interferometer for the Compact Toroidal Hybrid experiment.

A three-channel 1 mm wave interferometer has been designed, assembled, and installed on the Compact Toroidal Hybrid torsatron (CTH). The interferometer design makes novel use of a subharmonic mixer for detection, which simplifies alignment. It employs a single electronically tunable source that is repetitively chirped using a sawtooth waveform of frequency up to 1 MHz. The 15.25 GHz drive oscillator is multiplied in two stages to 122 GHz before a final doubler stage brings it to 244 GHz. Local oscillator (LO) power at 122 GHz is directed through waveguide to the LO input of the subharmonic mixer of each viewing chord, simplifying alignment. Phase detection is performed by directly digitizing the amplified mixer outputs at 50 MHz and processing them with a software algorithm. Initial measurements made with the central chord of the new interferometer agree with those from the existing 4 mm system at low densities. The 1 mm system performs well in current-driven discharges reaching densities over 10(19) m(-3), whereas the lower frequency interferometer is found to be less reliable due to loss of fringes. This is a critical improvement for experiments studying the onset, avoidance, and vacuum magnetic transform dependence of disruptions in the CTH device.

Intraosseous hemangioma of the clivus: a case report and review of the literature.

Intraosseous hemangiomas are benign vascular tumors that are encountered most commonly in vertebrae and rarely in the skull. When presenting in the skull, they are commonly found in the calvarium in frontal and parietal bones and seldom in the skull base. We encountered a patient with an incidental finding on magnetic resonance imaging (MRI) of an enhancing lesion in the clivus. Here we report an unusual location of a clival intraosseous hemangioma. A 62 year old man worked up for carpal tunnel syndrome had imaging of his cervical spine that revealed an enhancing clival lesion, which extended into the left occipital condyle. Endoscopic endonasal biopsy was performed on the abnormality revealing a capillary hemangioma. Patient tolerated the biopsy well and no further surgical intervention is indicated at this time. Patient will be followed at six month intervals. Primary intraosseus hemangiomas of the skull are extremely rare and usually occur in the calvarium. This is one of the few reported case of an intraosseus hemangioma in the clivus. We present this case in part because it is unusual, but more importantly, with the wider use of MRI, it is likely that these lesions will be discovered more frequently, and conceivably confused for more dangerous lesions.

Expression of inhibin/activin proteins and receptors in the human hypothalamus and basal forebrain.

The inhibin/activin family of proteins is known to have a broad distribution of synthesis and expression in many species, as well as a variety of functions in reproductive and other physiological systems. Yet, our knowledge regarding the production and function of inhibin and activin in the central nervous system is relatively limited, especially in humans. The present study aimed to explore the distribution of inhibin/activin protein subunits and receptors in the adult human brain. The human hypothalamus and surrounding basal forebrain was examined using post-mortem tissues from 29 adults. Immunocytochemical studies were conducted with antibodies directed against the inhibin/activin α, ßA, and ßB subunits, betaglycan and the activin type IIA and IIB receptors. An immunoassay was also utilised to measure dimeric inhibin A and B levels in tissue homogenates of the infundibulum of the hypothalamus. Robust ßA subunit immunoreactivity was present in the paraventricular, supraoptic, lateral hypothalamic, infundibular, dorsomedial and suprachiasmatic nuclei of the hypothalamus, in the basal ganglia, and in the nucleus basalis of Meynert. A similar staining distribution was noted for the ßB subunit, betaglycan and the type II receptor antibodies, whereas α subunit staining was not detected in any of the major anatomical regions of the human brain. Inhibin B immunoreactivity was present in all tissues, whereas inhibin A levels were below detectable limits. These studies show for the first time that the inhibin/activin protein subunits and receptors can be co-localised in the human brain, implicating potential, diverse neural functions.

Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel.

PURPOSE: We investigated whether serum markers of angiogenesis endothelin-1 (ET-1) and tissue factor (TF), and/or markers of vascular damage such as circulating endothelial cells (CECs), or their relative changes during treatment, were prognostic for overall survival (OS) in castration resistant prostate cancer (CRPC) patients. Additionally, we combined these markers with circulating tumour cells (CTCs) to construct a predictive nomogram for treatment outcome. PATIENTS AND METHODS: One hundred and sixty two CRPC patients treated with a docetaxel containing regimen had blood drawn before and at 2-5 weeks and 6-8 weeks after treatment start. Prospectively determined CTC and CEC levels, and retrospectively measured serum concentrations of ET-1 (pg/mL) and TF (pg/mL) were evaluated to determine their prognostic value for OS. RESULTS: Baseline CEC, TF and ET-1 were not prognostic for OS. A > or = 3.8-fold increase in CEC 2-5 weeks after treatment initiation was associated with decreased OS (median 10.9 versus 16.8 months; P=0.015), as was any decrease in TF levels compared to baseline levels (median 11.9 versus 21.5 months; P=0.0005). As previously published, baseline and CTC counts > or = 5 at 2-5 weeks were also predictive of decreased OS. Combining CTC with changes in TF and CEC 2-5 weeks after treatment initiation yielded four groups differing in OS (median OS 24.2 versus 16.0 versus 11.4 versus 6.1 months; P<0.0001). CONCLUSION: CEC, CTC and TF levels alone and combined can predict early on OS in CRPC patients treated with docetaxel-based therapy. A prospective study to confirm the use of these markers for patient management is needed.

Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents.

BACKGROUND: Early predictive markers for response are needed for advanced colorectal cancer (ACC) patients. We assessed the value of circulating tumour cells (CTC) in ACC patients treated with chemotherapy plus targeted agents (CAIRO2 phase III trial) and compared the results with computed tomography (CT) imaging. MATERIALS AND METHODS: CTC were determined at baseline and at different time points during treatment. Patients were stratified into low (less than three CTC per 7.5 ml of blood) or high CTC (three or more CTC per 7.5 ml of blood). RESULTS: A total of 467 patients were assessable for CTC analysis. Among them, 129 patients (29%) with high baseline CTC had a significantly decreased progression-free survival [PFS; hazard ratio (HR) 1.5] and overall survival (OS; HR 2.2) compared with 322 patients with low baseline CTC. This difference remained statistically significant during treatment. The sensitivity and specificity of high CTC at baseline for the prediction of progressive disease on CT imaging were 16.7% and 70.1%, respectively, and of high CTC at 1-2 weeks after the start of treatment 20.0% and 95.1%, respectively. The combined analysis of CTC and CT imaging provided a more accurate outcome assessment than either modality alone. CONCLUSIONS: The CTC count before and during treatment independently predicts PFS and OS in ACC patients treated with chemotherapy plus targeted agents and provides additional information to CT imaging.

Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer.

BACKGROUND: We evaluated the relationship between the detection and prognostic significance of circulating tumor cells (CTCs) and sites of metastases detected by 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: From May 2004 to January 2008, 195 patients with relapsed/progressive MBC underwent whole-body FDG-PET/CT and provided blood samples for assessment of CTC count. RESULTS: Higher CTC numbers were detected in patients with bone metastases relative to those with no bone lesions (mean 65.7 versus 3.3, P = 0.0122) and in patients with multiple bone metastases relative to those with one or two bone lesions (mean 77.7 versus 2.6, P < 0.001). CTCs predicted overall survival (OS) in 108 patients with multiple sites of metastases including bone (P = 0.0008) but not in 58 without bone metastases (P = 0.4111) and in 29 with bone involvement only (P = 0.3552). All 15 patients but one with human epidermal growth factor receptor 2 (HER-2) positive tumors who were treated with trastuzumab-based regimens had <5 CTCs at progression. In multivariate analysis, CTCs, but not bone metastases, remained a significant predictor of OS. CONCLUSION: Presence of extensive bone metastases as detected by FDG-PET/CT is associated with increased CTC numbers in MBC.

An instrument for combining x-ray multiple diffraction and x-ray topographic imaging for examining crystal microcrystallography and perfection.

Diffraction imaging using x-ray topography (XRT) and x-ray multiple diffraction (XRMD) provide valuable tools for examining the growth defects in crystals and the distributions from ideal lattice symmetry (microcrystallography). The topographic x-ray multiple diffraction microprobe (TMDM) combines the complementary aspects of both techniques enabling XRT and XRMD studies within the same instrument providing a useful resource for the structural characterization of materials that are not very stable in vacuum and electron beam environments. The design of the TMDM instrument is described together with data taken on GaAs (001) and potassium dihydrogen phosphate (001).

Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer.

BACKGROUND: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs. PATIENTS AND METHODS: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of > or = 3 or <3 CTCs/7.5 ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P = 0.004 for PFS; 9.4 versus 20.6 m, P < 0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P < 0.001). In patients receiving first- or second-line therapy (P = 0.003), irinotecan (P = 0.0001), having liver involvement (P = 0.002), >/=65 years (P = 0.0007), and ECOG PS of zero (P = 0.04), unfavorable baseline CTC was associated with inferior PFS. CONCLUSION: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.

Probes for measuring fluctuation-induced Maxwell and Reynolds stresses in the edge of the Madison Symmetric Torus reversed field pinch.

Several probes have been constructed to measure fluctuation-induced Maxwell and Reynolds stresses in the edge of the Madison Symmetric Torus reversed field pinch (RFP). The magnetic probe is composed of six magnetic pickup coil triplets. The triplets are separated spatially, which allows for local measurements of the Maxwell stress. To measure the plasma flow components for evaluation of the Reynolds stress, we employ a combination of an optical probe [Kuritsyn et al., Rev. Sci. Indrum. 77, 10F112 (2006)] and a Mach probe. The optical probe measures the radial ion flow locally using Doppler spectroscopy. The Mach probe consists of four current collectors biased negatively with respect to a reference tip and allows for measurements of the poloidal and toroidal components of the bulk plasma flow. The stresses are observed to play an important role in the momentum balance in the RFP edge during internal reconnection events.

Evidence for high-efficiency laser-heated hohlraum performance at 527 nm.

A series of experiments conducted on the HELEN laser system [M. J. Norman, Appl. Opt.4120023497], into thermal x-ray generation from hohlraum targets using 527 nm (2omega) wavelength laser light, has shown that it is possible to exceed radiation temperatures previously thought limited by high levels of superthermal or hot electron production or stimulated backscatter. This Letter questions whether the assumptions traditionally applied to hohlraum design with respect to hot plasma filling and the use of 2omega light are too conservative.