In situ process quality monitoring and defect detection for direct metal laser melting.

Quality control and quality assurance are challenges in direct metal laser melting (DMLM). Intermittent machine diagnostics and downstream part inspections catch problems after undue cost has been incurred processing defective parts. In this paper we demonstrate two methodologies for in-process fault detection and part quality prediction that leverage existing commercial DMLM systems with minimal hardware modification. Novel features were derived from the time series of common photodiode sensors along with standard machine control signals. In one methodology, a Bayesian approach attributes measurements to one of multiple process states as a means of classifying process deviations. In a second approach, a least squares regression model predicts severity of certain material defects.

Hepatocellular Carcinoma Cells Are Protected From Immunolysis by Mesenchymal Stromal Cells Through Indoleamine 2,3 Dioxygenase.

B7 family proteins serve as checkpoint molecules that protect tumors from T cell mediated lysis. Tryptophan degrading enzymes indoleamine 2,3 dioxygenase (IDO) and tryptophan 2,3 dioxygenase (TDO) also induce T cell immune tolerance. However, little is known about the relative contribution of B7 molecules, tryptophan degrading enzymes, as well as the impact of tumor and stromal cell interactions to the development of immunosuppressive tumor microenvironment. To investigate such interactions, we used a tripartite model of human hepatocellular carcinoma cell line (HepG2) and mesenchymal stromal cells (MSCs) co-cultured with peripheral blood mononuclear cells (PBMCs). Co-culture of HepG2 cells and activated PBMCs demonstrate that HepG2 cells undergo PBMC mediated cytolysis, despite constitutive expression of B7-H3 and upregulation of PD-L1 by IFNγ. Knockdown of B7-H3, PD-L1 or IDO does not modulate PBMC mediated lysis of HepG2 cells. However, TNFα preactivation enhances lysis of HepG2 cells, and blocking of TNFα production from PBMCs protects HepG2 cells. On the other hand, MSCs protect HepG2 cells from PBMC mediated lysis, even in the presence of TNFα. Further investigation showed that MSC mediated protection is associated with the unique secretome profile of upregulated and downregulated cytokines and chemokines. IFNγ activated MSCs are superior to TNFα activated or control MSCs in protecting HepG2 cells. Blockade of IFNγ driven IDO activity completely abolishes the ability of MSCs to protect HepG2 cells from cytolysis by PBMCs. These results suggest that inhibition of IFNγ activation of IDO induction in stromal cells, combined with usage of TNFα, could be a novel immunotherapeutic strategy to induce regression of hepatocellular carcinoma.

Comparison of acute responses to isotonic or isokinetic eccentric muscle action: differential outcomes in skeletal muscle damage and implications for rehabilitation.

Both isotonic and isokinetic eccentric muscle contractions are commonly used in muscle research laboratories to induce muscle damage, yet, the muscle damage outcomes between these 2 modes of eccentric contraction have not been compared. The purpose of this study was to compare modes of contraction for differences in muscle damage. 16 men were placed in the isotonic (IT: 110% of maximal isometric torque) or the isokinetic (IK: 120°/s) group, with each group performing 200 eccentric muscle actions of the knee extensors. Isometric peak torque, perceived soreness and CK activity were measured immediately pre and post exercise, and 48-h post exercise. Mean total work (~1700 J) and peak torque per set (~265 Nm) decreased over the 200 repetitions (p<0.01), and was not different between groups. Damage markers changed 48-h post exercise (p<0.05): peak isometric torque (-13%), creatine kinase activity (+200%) and self-perceived muscular soreness (+4 unit change). Significant group×time interactions (p<0.01) indicated that peak isometric torque was 22% lower, and creatine kinase and self-perceived muscular soreness were 330% and 3 unit difference higher in the IT as compared to the IK groups, 48-h post exercise. When equating for total work, skeletal muscle damage markers are higher during IT vs. IK modes. This reflects differences inherent in contraction type and suggests that this should be taken into account during physical rehabilitation.

Inhibition of monoamine oxidase isoforms modulates nicotine withdrawal syndrome in the rat.

AIMS: There have been many reports of monoamine oxidase (MAO) inhibition by non-nicotine ingredients in tobacco smoke, persisting for days after smoking cessation. This study determined the effect of inhibiting MAO and its isoforms on nicotine withdrawal syndrome. MAIN METHODS: Rats were rendered nicotine-dependent by seven days of subcutaneous (s.c.) 9 mg/kg/day infusion of nicotine bitartrate. Twenty-two hours after termination of infusion, they were observed over 20 min for somatically expressed nicotine withdrawal signs. Three hours before observation, rats were injected intraperitoneally (i.p.) with 4 mg/kg each of the MAO A antagonist clorgyline and the MAO B antagonist deprenyl, or with saline alone. A similar experiment was performed with non-dependent, saline-infused rats. Another experiment compared nicotine-dependent rats that received injections of either saline or 4 mg/kg clorgyline alone. A further experiment compared rats receiving either saline or 4 mg/kg deprenyl alone. KEY FINDINGS: Combined treatment with both MAO inhibitors markedly and significantly exacerbated somatically expressed nicotine withdrawal signs in nicotine infused rats, while having no significant effects in saline-infused rats. Rats injected s.c. with 4 mg/kg clorgyline alone had significantly more withdrawal signs than saline-injected rats, while deprenyl-injected rats had significantly fewer signs than saline controls. Assays confirmed that clorgyline thoroughly reduced MAO A enzymatic activity and deprenyl thoroughly reduced MAO B activity. SIGNIFICANCE: The results suggest that inhibition of MAO A may contribute to the intensity of withdrawal syndrome in smoking cessation.

Feasibility of conditioning with thymoglobulin and reduced intensity TBI to reduce acute GVHD in recipients of allogeneic SCT.

Murine studies using anti-T-cell antibodies for conditioning in allogeneic SCT demonstrate engraftment with low rates of GVHD. On the basis of this preclinical model, we conditioned 30 patients with advanced hematologic malignancies with rabbit antithymocyte globulin (ATG) and TBI, to reduce rates of fatal acute GVHD. Patients were enrolled in two sequential groups: cohort 1 received ATG 10 mg/kg in divided doses (days -4 to -1)+200 cGy TBI (n=16), and cohort 2 received ATG (days -10 to -7)+450 cGy TBI (n=14). Median donor blood chimerism for the combined group was 94, 93 and 93% in the first, second and third months after transplant. Only three developed grade II acute GVHD despite 43% of patients receiving unrelated donor transplants. One-year survival was 71+/-11 and 54+/-14%, respectively, in recipients of related and unrelated donor SCT. Donor lymphocyte infusions were needed in 12 patients for the management of relapse and for mixed donor-recipient chimerism in 4 patients. We conclude that 10 mg/kg ATG and TBI allows engraftment with a low risk of acute GVHD; however, further dose optimization of ATG is required to achieve a balance between GVHD and disease relapse.

Clinical results of Maverick lumbar total disc replacement: two-year prospective follow-up.

Disc prosthesis is the new treatment for degenerative disc disease in the lumbar spine. Key to assessing the interest in this new motion technique is evaluating the results in terms of functional and radiologic outcomes. This prospective study reports the outcome of 64 Maverick devices implanted between January 2002 and November 2003. The degree of improvement was equivalent to that obtained with anterior fusion cages using the mini-invasive technique. Radiographic follow-up in this series showed a degree of mobility close to normal. The technique is safe because the intra- and postoperative complication rate is low. The Oswestry score improved for 75% of patients. This improvement is significantly correlated with facet arthrosis and muscle fatty degeneration.

The effect of single-level, total disc arthroplasty on sagittal balance parameters: a prospective study.

A prospective radiographic study of the influence of total disc replacement on spinal sagittal balance. The goal of this study was to prospectively determine the effect of a single-level, total disc replacement on the sagittal balance of the spine, especially on sacral tilt (ST), pelvic tilt (PT), and lumbar lordosis. It has been shown that lumbar fusion may deleteriously alter the sagittal balance of the spine, including a decrease in the ST and lumbar lordosis. Clinically, postfusion pain has been shown to be significantly related to a decreased ST, increased PT, and decreased lumbar lordosis, independent of other factors such as pseudoarthrosis. To our knowledge, the influence of total disc replacement on spinal sagittal balance has not yet been reported in the literature. This is a prospective study of 35 patients who received a single level disc replacement using the Maverick Total Disc Arthroplasty system (Medtronic Sofamor Danek, Memphis, Tennessee) by a single surgeon at one institution from March 2002 to September 2003. The preoperative and postoperative radiographic evaluation included standing anteroposterior and lateral full spine films that included the femoral heads. The parameters studied were ST, PT, global and segmental lordosis, and global kyphosis. The average age of the 35 patients studied was 44.3 years (range 35-57). There were 18 females and 17 males. The disc arthroplasty was performed at the L4-L5 level in 19 patients and at the L5-S1 level in 16 patients. The average follow-up was 14 months (range 6-22 months). The preoperative values of global lordosis, ST, and PT were 51.5 degrees , 37.8 degrees , 16.9 degrees and, at last follow-up, they were 51.4 degrees , 37.4 degrees , and 17.5 degrees , respectively. These changes were not significantly different. When the groups were separated according to the level operated, there was still no statistical difference with regard to the overall lordosis, ST, PT or kyphosis from pre- to postoperative period or when the two groups were compared with each other. The level above the prosthesis has always significantly less lordosis. In the present study with use of a motion-preserving Maverick prosthesis, it appears that the patient is able to maintain the preoperative sagittal balance. The prosthesis has enough freedom of motion to allow the patient to maintain the natural sagittal and spinopelvic balance needed to prevent potential undue stress on the muscles and the sacroiliac joint. Although the number of patients is small, this is the first study to our knowledge that evaluates the sagittal balance after motion-preserving total disc arthroplasty.

Shock absorption in lumbar disc prosthesis: a preliminary mechanical study.

Lumbar disc prostheses have been used in treating symptomatic degenerative disc diseases. A few prostheses of the ball-socket design are currently available for clinical use, the joint mechanism being materialized either with a hard polymer core or a metal-to-metal couple. Other prostheses of "shock absorber" design were not available at the time of the study. The objective of this work was to establish whether there was a difference in the shock absorption capacity between a device having an ultra-high-molecular-weight polyethylene center core and a device having a metal-on-metal bearing. Vibration and shock loading were applied to two lumbar total disc prostheses: PRODISC, manufactured by Spine Solutions, and MAVERICK Total Disc Replacement, manufactured by Medtronic Sofamor Danek. The shock absorption capacity of the device was evaluated by comparing the input and the output force measurements. The disc prosthesis was mounted onto a test apparatus. Each side of the device was equipped with a force sensor. The input shock load and the output resulting forces were simultaneously measured and recorded. The loading force pattern included 1). a static preload of 350 N plus an oscillating vibration of 100 N with frequency sweeping from 0 to 100 Hz and 2). a sudden shock load of 250 N applied over a 0.1-second interval. Both input and output signal data were processed and were transformed into their frequency spectrums. The vibration and shock transmissibility of the device, defined as the ratio of the output spectrum over the input spectrum, were calculated in sweeping the frequency from 0 to 100 Hz. The phase deviation was calculated to characterize the shock absorber effects. For both tested devices under vibration and shock loading, the phase angle displacement between the input and the output signals was 10 degrees. Under oscillating vibration loading, both tested devices had a transmission ratio higher than 99.8%. Over the frequency interval 1-100 Hz, the difference in transmission ratio between the two devices was <0.3%. Under sudden shock loading, both tested devices had a transmission ratio higher than 98%. The difference between the two devices was <0.8%. Both tested devices have identical vibration and shock transmissibility.

Mismanaging prescription medications among rural elders: the effects of socioeconomic status, health status, and medication profile indicators.

PURPOSE: This study assessed the extent to which community-dwelling rural older adults mismanage their prescription medication regimens and predicted mismanagement of medications from selected socioeconomic, health status, and medication profile characteristics. DESIGN AND METHODS: Personal interviews with 499 community-dwelling adults aged 66 and over taking at least one prescription medication and living in a rural region of the Southeast. With approximately equal numbers of African American and white men and women, the SUDAAN multiple logistic regression procedure was used to predict the mismanagement of prescription medications. RESULTS: The mismanagement of prescribed medication regimens is relatively common among older adults. Those more likely than others to mismanage their regimens are African American, younger, in poorer mental health, with more acute care physician visits, and those who find payment for their medications to be problematic. IMPLICATIONS: The implications of the findings for what is known about the self-modification of drug regimens, targeting prescription drug cost benefits or interventions, and the limitations of the study are discussed.

Aberrant nuclear expression of AP-1 and NFkappaB in lymphocytes of women stressed by the experience of breast biopsy.

We have investigated the expression of AP-1 and NFkappaB in peripheral blood lymphocytes of women scheduled for breast biopsy. Samples were collected when women were informed of the need for biopsy (prebiopsy, T1, 5-7 days prior to the actual biopsy) and 7-10 days after they learned the result of their biopsy (postbiopsy, T2). At the time of blood collection, psychological stress was evaluated using Speilberger's State Trait Anxiety Inventory (STAI) and the Profile of Mood States (POMS). Women scheduled to undergo breast biopsy reported significant increases in anxiety (STAI) and mood disturbance (POMS). Gel shift mobility assays showed that mitogen stimulated peripheral blood lymphocytes of these women were less capable of the nuclear expression of AP-1 or NFkappaB at T1. Similar assessments, 7-10 days after the women learned of the results of their breast biopsy, showed these same women to have a marked reduction in anxiety and mood disturbance and an increased nuclear translocation of AP-1 and NFkappaB. These results show a significant decrease in nuclear AP-1 and NFkappaB expression during the period of emotional distress prior to biopsy with a return of nuclear transcription activity to normal levels when distress was relieved. Several studies have correlated increased psychological stress with decreased immune function. The results of this study suggest that psychological stress may mediate immunosuppression by altering the expression of the transcription factors, AP-1 and NFkappaB.

The association of race/ethnicity, socioeconomic status, and physician recommendation for mammography: who gets the message about breast cancer screening?

OBJECTIVES: This study investigated the association between physician recommendation for mammography and race/ethnicity, socioeconomic status, and other characteristics in a rural population. METHODS: In 1993 through 1994, we surveyed 1933 Black women and White women 52 years and older in 10 rural counties. RESULTS: Fifty-three percent of the women reported a physician recommendation in the past year. White women reported recommendations significantly more often than did Black women (55% vs 45%; odds ratio = 1.49). Controlling for educational attainment and income eliminated the apparent racial/ethnic difference. After control for 5 personal, 4 health, and 3 access characteristics, recommendation for mammography was found to be more frequent among women who had access to the health care system (i.e., had a regular physician and health insurance). Recommendation was less frequent among women who were vulnerable (i.e., were older, had lower educational attainment, had lower annual family income). CONCLUSIONS: Socioeconomic status, age, and other characteristics--but not race/ethnicity--were related to reports of a physician recommendation, a precursor strongly associated with mammography use. Efforts to increase physician recommendation should include complementary efforts to help women address socioeconomic and other barriers to mammography use.

Human thymic epithelial cells inhibit IL-15- and IL-2-driven differentiation of NK cells from the early human thymic progenitors.

T/NK progenitors are present in the thymus; however, the thymus predominantly promotes T cell development. In this study, we demonstrated that human thymic epithelial cells (TEC) inhibit NK cell development. Most ex vivo human thymocytes express CD1a, indicating that thymic progenitors are predominantly committed to the T cell lineage. In contrast, the CD1a(-)CD3(-)CD56(+) NK population comprises only 0.2% (n = 7) of thymocytes. However, we observed increases in the percentage (20- to 25-fold) and absolute number (13- to 71-fold) of NK cells when thymocytes were cultured with mixtures of either IL-2, IL-7, and stem cell factor or IL-15, IL-7, and stem cell factor. TEC, when present in the cultures, inhibited the increases in the percentage (3- to 10-fold) and absolute number (3- to 25-fold) of NK cells. Furthermore, we show that TEC-derived soluble factors inhibit generation of NK-CFU and inhibit IL15- or IL2-driven NK cell differentiation from thymic CD34(+) triple-negative thymocytes. The inhibitory activity was found to be associated with a 8,000- to 30,000 Da fraction. Thus, our data demonstrate that TEC inhibit NK cell development from T/NK CD34(+) triple negative progenitors via soluble factor(s), suggesting that the human thymic microenvironment not only actively promotes T cell maturation but also controls the development of non-T lineage cells such as the NK lineage.

Reduced levels of Hsp70 result in a therapeutic effect of 15-deoxyspergualin on acute graft-versus-host disease in (DA x LEW)F1 rats.

We have shown previously that increased levels of hsp70, and antibodies reactive with hsp70 parallel the onset and severity of graft-versus-host disease (GVHD) in a parent --> (DA x LEW)F1 rat model. In this study we have assessed the effect of reducing the levels of the 70 kDa heat shock protein (hsp70), on the morbidity and mortality of acute GVHD in (DA x LEW)F1 rats. The reduction was accomplished by the administration of 15-deoxyspergualin (DSG), an immunosuppressive agent which binds to a constitutively expressed member of the 70 kDa heat shock protein family. DSG administered via three different protocols reduced GVHD-associated morbidity. One of the regimens, which consisted of intermittent DSG administration, also significantly reduced GVHD associated mortality. This DSG treatment reduced hsp70 levels in spleen and lymph nodes, inhibited anti-hsp70 antibody production, and diminished the serum levels of IL-2, IFN-gamma, TNF-alpha, and IL-10. IL-4 levels in the serum did not change during GVHD and were not effected by DSG. These results show that the mechanism of DSG immunosuppressive effect in rat GVHD may involve DSG's capacity to bind to hsp70, which in turn may lead to a decrease in levels of circulating anti-hsp70 antibodies, and reduced production of cytokines.

Negotiating cultural consensus in a breast cancer self-help group.

This article describes a shared model of the breast cancer experience negotiated by the members of a spontaneously organized breast cancer self-help group in eastern North Carolina. In the course of sharing their personal experience narratives with one another, these women worked to negotiate points of agreement among the varying sources of knowledge and oftentimes conflicting belief systems they held about breast cancer. The synthetic model they created rejected many of the assumptions underlying the dominant biomedical view of cancer "survivorship," particularly its emphasis on the autonomous individual as decision maker and its attendant male-gendered sports and military imagery--assumptions that often implicitly structured the agendas and topics discussed in the formal, medically sanctioned support groups these women found unappealing. The implications for theories about the construction of shared cultural models and for continuing efforts to design support groups to meet the needs of a diverse patient population are explored.

Stress reduction and HIV disease: a review of intervention studies using a psychoneuroimmunology framework.

The field of psychoneuroimmunology (PNI) posits that relationships exist between stress, immunological impairment, and health outcomes. Accumulating evidence suggests that stress may hasten HIV disease progression by increasing viral replication, suppressing immune response, and inducing deleterious health-related behaviors. Interventions that attenuate the effects of stress are postulated to operate by altering cognitive perception and/or modulating neuroendocrine and sympathetic reactivity. A review of HIV/PNI intervention studies is presented as a guide for the inclusion of stress reduction interventions in comprehensive plans of care for HIV-infected individuals. Although effect and sample sizes are small, the results of these studies provide support for a positive effect of various interventions on immunological and health-related indices in HIV-infected individuals.

Stress and HIV disease progression: psychoneuroimmunological framework.

Psychoneuroimmunology (PNI) is the study of the interrelationships among behavior, neural and endocrine function, and the immune system. PNI investigates the relationships among stress, physiological dysregulation, and health outcomes. Research has supported the theory that emotional distress and the resultant neuroendocrine activation can induce immune system suppression. This suppression has significant implications for disease susceptibility and progression. HIV disease and its extensive immunological consequences are explored within this framework. Potential physiological pathways that may mediate stress-induced dysregulation within the context of HIV disease are identified. Key HIV-related PNI research studies are reviewed and critically analyzed. Implications for nursing practice and research are discussed.

Differential effects of glucocorticoids on colony stimulating factors produced by neonatal mononuclear cells.

The purpose of this study was to examine the effect of dexamethasone (DEX) on the production of granulocyte and granulocyte-macrophage colony stimulating factors (G-CSF and GM-CSF) by neonatal mononuclear cells. Mononuclear cells were isolated from umbilical cord blood and cultured with either phorbol myristate acetate/phytohemagglutinin (PMA/PHA) or Candida albicans with or without DEX (10(-8)-10(-6) M) for 48 h. Cell supernatants were assayed for G-CSF and GM-CSF by ELISA. Mononuclear cells from term and preterm infants responded to PMA/PHA stimulation with a significant increase in G-CSF production over baseline levels. The PMA/PHA-induced increase in G-CSF production was markedly augmented by the addition of DEX to cell cultures. DEX augmented production of G-CSF was significantly less in mononuclear cells from preterm infants. Similarly, production of G-CSF was significantly less by mononuclear cells from infants with acute physiology scores of > or = 10, as judged by the Score for Acute Neonatal Physiology. In contrast, DEX significantly inhibited PMA/PHA-induced GM-CSF production. Although C. albicans induced mononuclear cells to produce G-CSF, DEX did not significantly augment this production. No significant effect of DEX on C. albicans induced GM-CSF production was observed. The data show DEX induced differential regulation of infant peripheral blood mononuclear cell production of G-CSF and GM-CSF. These results suggest that glucocorticoids may enhance certain aspects of host immune function in addition to their well-documented immunosuppressive effects. Further, the neutrophilia observed in DEX-treated infants may be due to enhanced G-CSF production.

Reduced capacity of neonatal lymphocytes to inhibit the growth of Candida albicans.

Opportunistic microorganisms produce significant morbidity and mortality in preterm and term infants. Because of the heightened susceptibility of infants to opportunistic fungal infections, neonatal lymphocytes were assessed for their capacity to inhibit the growth of Candida albicans. Lymphocytes from both preterm and term cord blood demonstrated significantly less effect upon C. albicans than did lymphocytes from adults. Neonatal lymphocytes of infants <32 weeks of gestation showed a marked reduction in growth inhibitory capacity compared to infants >32 weeks of gestation. Lymphocytes from female infants had a significantly greater fungal growth inhibitory capacity than did lymphocytes from male infants. These results show that neonatal lymphocytes have a reduced capacity to inhibit the growth of C. albicans. This reduced antifungal capacity may underlie the increased susceptibility of such infants to opportunistic microorganisms, like C. albicans.

Antifungal activity of interleukin-2-activated natural killer (NK1.1+) lymphocytes against Candida albicans.

Interleukin-2 (IL-2)-activated lymphocytes interact directly with, and inhibit, the growth of Candida albicans hyphae. C. albicans-stimulated natural killer (NK1.1+) lymphocytes were demonstrated to secrete a soluble product capable of directly affecting C. albicans yeast forms. Antibodies specific for interferon-gamma completely eliminated the antifungal activity of the NK1.1+ lymphocyte product and diminished the antifungal activity of NK1.1+ lymphocytes against C. albicans. Antibodies specific for other cytokines had no such effect. These data demonstrate that C. albicans-stimulated NK1.1+ lymphocytes have antifungal activity against C. albicans yeast cells via the release of interferon-gamma. This antifungal activity was demonstrable only against the yeast form of the fungus, with no effect on C. albicans hyphae.

Effect of Pichia anomala killer toxin on Candida albicans.

The effect of a Pichia anomala killer toxin upon a Candida albicans-sensitive strain was studied. Yeast and hyphae, after treatment with the toxin, were less capable of uptaking either [3H]-uridine or [35S]-methionine. In addition, the hyphal form of the fungus appeared to be less capable of DNA synthesis after toxin treatment. No effect of the killer toxin was shown upon a natural resistant mutant of the source strain. These data suggest that, similar to other killer yeast toxins, the toxin of P. anomala can produce a number of quantifiable effects upon sensitive C. albicans cells.