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Because the efficacy of new drugs reported in trials may not translate into similar results when used in the real‐life, we analyzed the efficacy of idelalisib and rituximab (IR) in 149 patients with relapsed/refractory chronic lymphocytic leukemia treated at 34 GIMEMA centers. Median progression‐free survival (PFS) and overall survival were 22.9 and 44.5 months, respectively; performance status (PS) ≥2 and ≥3 previous lines of therapy were associated with shorter PFS and overall survival (OS). 48% of patients were on treatment at 12 months; the experience of the centers (≥5 treated patients) and PS 0–1 were associated with a significantly longer treatment duration (p = 0.015 and p = 0.002, respectively). TP53 disruption had no prognostic significance. The overall response rate to subsequent treatment was 49.2%, with median OS of 15.5 months and not reached in patients who discontinued, respectively, for progression and for toxicity (p

Iron oxides are Group 3 (not classifiable as to its carcinogenicity to humans) according to the International Agency for Research on Cancer (IARC). Occupational exposures during iron and steel founding and hematite underground mining as well as other iron predominant exposures such as welding are Group 1 (carcinogenic to humans). The objective of this study was to investigate the potential of iron as iron (III) oxide (Fe(2)O(3)) to initiate lung tumors in A/J mice, a lung tumor susceptible strain. Male A/J mice were exposed by oropharyngeal aspiration to suspensions of Fe(2)O(3) (1 mg) or calcium chromate (CaCrO(4); 100 μg; positive control) for 26 weeks (once per week). Shams were exposed to 50 μL phosphate buffered saline (PBS; vehicle). Mice were euthanized 70 weeks after the first exposure and lung nodules were enumerated. Both CaCrO(4) and Fe(2)O(3) significantly increased gross-observed lung tumor multiplicity in A/J mice (9.63 ± 0.55 and 3.35 ± 0.30, respectively) compared to sham (2.31 ± 0.19). Histopathological analysis showed that bronchiolo-alveolar adenomas (BAA) and carcinomas (BAC) were the primary lung tumor types in all groups and were increased in the exposed groups compared to sham. BAC were significantly increased (146 %) in the CaCrO(4) group and neared significance in the Fe(2)O(3) group (100 % increase; p = 0.085). BAA and other histopathological indices of toxicity followed the same pattern with exposed groups increased compared to sham control. In conclusion, evidence from this study, in combination with our previous studies, demonstrate that exposure to iron alone may be a potential risk factor for lung carcinogenesis.

Welding fumes were reclassified as a Group 1 carcinogen by the International Agency for Research on Cancer in 2017. Gas metal arc welding (GMAW) is a process widely used in industry. Fume generated from GMAW-mild steel (MS) is abundant in iron with some manganese, while GMAW-stainless steel (SS) fume also contains significant amounts of chromium and nickel, known carcinogenic metals. It has been shown that exposure to GMAW-SS fume in A/J mice promotes lung tumors. The objective was to determine if GMAW-MS fume, which lacks known carcinogenic metals, also promotes lung tumors in mice. Male A/J mice received a single intraperitoneal injection of corn oil or the initiator 3-methylcholanthrene (MCA; 10 μg/g) and, one week later, were exposed by whole-body inhalation to GMAW-MS aerosols for 4 hours/day x 4 days/week x 8 weeks at a mean concentration of 34.5 mg/m3. Lung nodules were enumerated by gross examination at 30 weeks post-initiation. GMAW-MS fume significantly increased lung tumor multiplicity in mice initiated with MCA (21.86 ± 1.50) compared to MCA/air-exposed mice (8.34 ± 0.59). Histopathological analysis confirmed these findings and also revealed an absence of inflammation. Bronchoalveolar lavage analysis also indicated a lack of lung inflammation and toxicity after short-term inhalation exposure to GMAW-MS fume. In conclusion, this study demonstrates that inhalation of GMAW-MS fume promotes lung tumors in vivo and aligns with epidemiologic evidence that shows MS welders, despite less exposure to carcinogenic metals, are at an increased risk for lung cancer.

The exposome is the measure of all exposures of an individual in a lifetime and how those exposures relate to health. The goal was to examine an experimental model integrating multiple aspects of the exposome by collecting biological samples during critical life stages of an exposed animal that are applicable to worker populations. Genetic contributions were assessed using strains of male rats with different genetic backgrounds (Fischer-344, Sprague Dawley, and Brown-Norway) maintained on a regular or high-fat diet for 24 weeks. At week 7 during diet maintenance, groups of rats from each strain were exposed to stainless steel welding fume (WF; 20 mg/m3 × 3 h/d × 4 days/week × 5 weeks) or air until week 12, at which time some animals were euthanized. A separate set of rats from each strain were allowed to recover from WF exposure until the end of the 24-week period. Bronchoalveolar lavage fluid and serum were collected at 7, 12, and 24 weeks to assess general health indices. Depending on animal strain, WF exposure and high-fat diet together worsened kidney toxicity as well as altered different serum enzymes and proteins. Diet had minimal interaction with WF exposure for pulmonary toxicity endpoints. Experimental factors of diet, exposure, and strain were all important, depending on the health outcome measured. Exposure had the most significant influence related to pulmonary responses. Strain was the most significant contributor regarding the other health indices examined, indicating that genetic differences possibly drive the exposome effect in each strain.

Millions of workers in the US and worldwide are exposed to complex, metal-rich welding fumes. Although welding is a crucial industrial process, the generated fumes are known to cause acute and chronic health effects when inhaled. The International Agency for Research on Cancer (IARC) classified welding fumes as carcinogenic to humans (Group 1) in 2017, based on sufficient epidemiological evidence and limited evidence in animals, an upgrade from the former Group 2B (possibly carcinogenic to humans) classification. There is human evidence that both iron-abundant mild steel as well as chromium- and nickel-containing stainless steel welding fumes contribute to an increased risk of lung cancer. Recent animal studies show that welding fumes may act as lung tumor promoters, regardless of the presence or absence of potentially carcinogenic metals, such as chromium and nickel. The goal of this manuscript was to examine the pulmonary responses associated with welding fumes by reviewing a series of recent experimental animal studies that assessed the influence of welding fume metal composition (e.g., stainless steel versus mild steel welding fume) on markers of lung toxicity and tumor development. Additional in vivo laboratory studies are needed to further explore the association between welding and lung cancer and to help advance our understanding of a potential mechanistic link.

Pulmonary toxicity studies often use bronchoalveolar lavage (BAL) to investigate potential adverse lung responses to a particulate exposure. The BAL cellular fraction is counted, using automated (i.e. Coulter Counter®), flow cytometry or manual (i.e. hemocytometer) methods, to determine inflammatory cell influx. The goal of the study was to compare the different counting methods to determine which is optimal for examining BAL cell influx after exposure by inhalation or intratracheal instillation (ITI) to different particles with varying inherent pulmonary toxicities in both rat and mouse models. General findings indicate that total BAL cell counts using the automated and manual methods tended to agree after inhalation or ITI exposure to particle samples that are relatively nontoxic or at later time points after exposure to a pneumotoxic particle when the response resolves. However, when the initial lung inflammation and cytotoxicity was high after exposure to a pneumotoxic particle, significant differences were observed when comparing cell counts from the automated, flow cytometry and manual methods. When using total BAL cell count for differential calculations from the automated method, depending on the cell diameter size range cutoff, the data suggest that the number of lung polymorphonuclear leukocytes (PMN) varies. Importantly, the automated counts, regardless of the size cutoff, still indicated a greater number of total lung PMN when compared with the manual method, which agreed more closely with flow cytometry. The results suggest that either the manual method or flow cytometry would be better suited for BAL studies where cytotoxicity is an unknown variable.

Rationale and objectives Whether expectations about future health are adaptive or maladaptive in late life likely depends on the extent to which they conform to or defy a future reality of declining health. Our premise was that, when adults face a downward spiral in health, it can be adaptive to realistically expect poorer future health and maladaptive to unrealistically expect good health. Method This 18-year-long study of community-dwelling older Canadians (n = 132, 72–98 years) involved a baseline interview to identify those who anticipated heath would decline (pessimistic expectation) or improve/remain stable (optimistic expectation). We determined initial (baseline) health status by assessing the severity of chronic conditions. An objective within-person measure of actual health change was derived by documenting hospital admissions (HAs) over time to capture a continuum that ranged from no declines (HAs remained stable) to greater declines in health (increasing numbers of HAs). Our a priori hypotheses examined the effects of health expectations (pessimistic, optimistic) and actual health change on the outcomes of depressive symptoms and mortality. Results Support was found for our premise that it is adaptive to be realistic when forecasting future health, at least at low levels of initial chronic condition severity. Regression analyses showed that realistically pessimistic (vs. unrealistically optimistic) expectations predicted significantly fewer depressive symptoms and a lower risk of death. The results also supported our premise that it is maladaptive to be unrealistically optimistic when health subsequently declines in reality: The risk of death was 313% higher for those with optimistic expectations that were unrealistic (vs. realistic). Conclusion These findings provide insights for health care professionals regarding the messages they communicate to their patients. Together, they imply that, when good health is slipping away, it seems optimal to encourage a healthy dose of realism.

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m³ to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (R(L)) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline R(L) was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased R(L) and result in endothelial dysfunction, but otherwise had minor effects on the lung.

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/ cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged

OBJECTIVE: Although amphibians are known Salmonella carriers, no such outbreaks have been reported. We investigated a nationwide outbreak of human Salmonella Typhimurium infections occurring predominantly among children from 2008 to 2011. METHODS: We conducted a matched case-control study. Cases were defined as persons with Salmonella Typhimurium infection yielding an isolate indistinguishable from the outbreak strain. Controls were persons with recent infection with Salmonella strains other than the outbreak strain and matched to cases by age and geography. Environmental samples were obtained from patients’ homes; traceback investigations were conducted. RESULTS: We identified 376 cases from 44 states from January 1, 2008, to December 31, 2011; 29% (56/193) of patients were hospitalized and none died. Median patient age was 5 years (range CONCLUSIONS: ADFs were the source of this nationwide pediatric predominant outbreak. Pediatricians should routinely inquire about pet ownership and advise families about illness risks associated with animals.

Epidemiologic studies suggest an increased risk of lung cancer with exposure to welding fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected “aged” gas metal arc–stainless steel (GMA–SS) welding fume has been shown by our laboratory to promote lung tumor formation in vivo using a two-stage initiation–promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS welding fume also acts as a lung tumor promoter in lung tumor-susceptible mice. Male A/J mice received intraperitoneal (IP) injections of corn oil or the chemical initiator 3-methylcholanthrene (MCA; 10 μg/g) and 1 week later were exposed by whole-body inhalation to air or GMA-SS welding aerosols for 4 h/d × 4 d/w × 9 w at a target concentration of 40 mg/m(3). Lung nodules were enumerated at 30 weeks post-initiation. GMA-SS fume significantly promoted lung tumor multiplicity in A/J mice initiated with MCA (16.11 ± 1.18) compared to MCA/air-exposed mice (7.93 ± 0.82). Histopathological analysis found that the increased number of lung nodules in the MCA/GMA-SS group were hyperplasias and adenomas, which was consistent with developing lung tumorigenesis. Metal deposition analysis in the lung revealed a lower deposited dose, approximately fivefold compared to our previous aspiration study, still elicited a significant lung tumorigenic response. In conclusion, this study demonstrates that inhaling GMA-SS welding fume promotes lung tumorigenesis in vivo which is consistent with the epidemiologic studies that show welders may be at an increased risk for lung cancer.

Reaching out to faculty about library resources and services is an ongoing and sometimes mysterious process for vendors and librarians alike—one that, when effective, can contribute a higher ROI and improved collaboration between libraries and publishers. However, it can be a challenge to reach that sweet spot between “effective” and “annoying,” especially in the face of seemingly nonresponsive faculty. A physical and life sciences librarian and former head of collection development and acquisitions from the University of Central Florida (UCF), and a Springer account development specialist, who works closely with academic librarians, weigh in on four different issues about improving outreach and identifying opportunities for outreach and collaboration.

Arc welding processes generate complex aerosols composed of potentially hazardous metal fumes and gases. Millions of workers worldwide are exposed to welding aerosols daily. A health effect of welding that is of concern to the occupational health community is the development of immune system dysfunction. Increased severity, frequency, and duration of upper and lower respiratory tract infections have been reported among welders. Specifically, multiple studies have observed an excess mortality from pneumonia in welders and workers exposed to metal fumes. Although several welder cohort and experimental animal studies investigating the adverse effects of welding fume exposure on immune function have been performed, the potential mechanisms responsible for these effects are limited. The objective of this report was to review both human and animal studies that have examined the effect of welding fume pulmonary exposure on local and systemic immune responses.

Objective: Interest exists for early monitoring of worker exposure to engineered nanomaterials. Here, we highlight quantitative systemic markers of early effects after carbon nanotube (CNT) exposure. Methods: Mice were exposed by pharyngeal aspiration to 40-μg CNT and harvested 24 hours, 7 days, and 28 days postexposure for measurements of whole blood, lung and extrapulmonary tissue gene expression, blood and bronchoalveolar lavage (BAL) differentials, and serum protein profiling. Results: Early effects included increased inflammatory blood gene expression and serum cytokines followed by an acute phase response (eg, CRP, SAA-1, SAP). Beyond 24 hours, there was a consistent increase in blood and BAL eosinophils. At 28 day, serum acute phase proteins with immune function including complement C3, apolipoproteins A-I and A-II, and α2-macroglobulin were increased. Conclusions: Carbon nanotube exposure resulted in measurable systemic markers but lacked specificity to distinguish from other pulmonary exposures.

Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at-risk population for development of lung cancer. Our objective was to expose, by inhalation, lung tumor susceptible (A/J) and resistant C57BL/6J (B6) mice to stainless steel (SS) welding fume containing carcinogenic metals and characterize the lung-inflammatory and tumorigenic response. Male mice were exposed to air or gas metal arc (GMA)-SS welding fume at 40 mg/m(3)×3 h/day for 6 and 10 days. At 1, 4, 7, 10, 14, and 28 days after 10 days of exposure, bronchoalveolar lavage (BAL) was done. Lung cytotoxicity, permeability, inflammatory cytokines, and cell differentials were analyzed. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 78 weeks after 6 and 10 days of exposure. Inhalation of GMA-SS fume caused an early, sustained macrophage and lymphocyte response followed by a gradual neutrophil influx and the magnitudes of these differed between the mouse strains. Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α) were increased in both strains while the B6 also had increased interleukin-6 (IL-6) protein. BAL measures of cytotoxicity and damage were similar between the strains and significantly increased at all time points. Histopathology and tumorigenesis were unremarkable at 78 weeks. In conclusion, GMA-SS welding fume induced a significant and sustained inflammatory response in both mouse strains with no recovery by 28 days. Under our exposure conditions, GMA-SS exposure resulted in no significant tumor development in A/J mice.

Research indicates that the financial literacy of U.S. teens is low, yet they have access to and spend a great deal of money each year. Teens were surveyed in 1998 (N = 323) and again in 2008 (N = 558) to determine what teens wanted to know about money and how they wanted to learn. Data were collected regarding teens’ sources of income, why money was important, the types of financial information they would like to learn, and how they would like to learn from seven counties in California—Alameda, Kern, Los Angeles, Riverside, San Diego, San Luis Obispo, and Santa Barbara. The findings indicate that teens are still interested in learning about many of the same financial topics identified in 1998, but their desire for web education has increased. These data can be used to develop programs that will interest teens.

Information about folate intake among low-income women of childbearing age remains limited. This report presents results from a cross-sectional study of folate intake and food-related behaviors in a sample of low-income, nonpregnant women of childbearing age in California. One hundred fifty-seven nonpregnant, low-income (≤185% federal poverty level) women of childbearing age (18 to 45 years) were evaluated for usual intake of natural food folate and synthetic folic acid, as well as specific food-related behaviors. Eighty-five percent of participants met the Recommended Dietary Allowance for folate, but only 37% met the current synthetic folic acid recommendation for reducing the risk of neural tube defects. Intake of naturally occurring food folate and intake of synthetic folic acid from supplements were positively associated with overall healthful food-related behaviors. Nutrition education that includes information about folic acid may be one way to improve folate intake and other healthful food behaviors among low-income women of childbearing age.

SUMMARY Laws and regulations govern many aspects of life in order to guide and protect individuals. The Food and Drug Administration regulates the development, production and marketing of foods, pharmaceuticals, and biotechnologies to maintain safe and high quality products for consumers. However, in recent years, food manufacturers seem to have forged ahead of the FDA's regulations and entered uncharted, unregulated areas. This paper examines the impact the FDA has on new food product development, particularly the impact on new technological food products and suggests the use of a team-based approach in evaluating and establishing regulations in the food industry.

Conflicting evidence exists as to whether nitric oxide expresses damaging/inflammatory or antioxidant/anti-inflammatory properties. Data presented in this review indicate that in vitro or in vivo exposure to selected environmental or occupational agents, such as asbestos, silica, ozone or lipopolysaccharide, can result in up-regulation of inducible nitric oxide synthase by alveolar macrophages and pulmonary epithelial cells. In the case of silica exposure, evidence consistently supports a damaging/inflammatory role of nitric oxide and/or peroxynitrite in the pathogenesis of lung disease. Although conflicting data have been reported, the majority of published studies suggest that nitric oxide plays a damaging role in pulmonary injury resulting from exposure to ozone or asbestos. In contrast, most information supports an anti-inflammatory role of nitric oxide following exposure to lipopolysaccharide. Further investigation is required to elucidate fully the mechanisms involved in determining the role of nitric oxide in the initiation and progression of various pulmonary diseases.

University administrators and instructors typically expect their academic programs to educate students to become relatively mature scholars. The American philosopher, Mortimer Adler (Reforming education: the opening of the American mind. Collier Macmillan, New York, 1988), says that a mature scholar is “a person who has a good mind, well disciplined in its processes of inquiring and judging, knowing and understanding, and well furnished with knowledge, well cultivated by ideas” (pp. 109–110). In this chapter, we consider both institutional and student factors that facilitate the realization of this objective. First, universities should provide well-structured courses and programs that are specifically designed to help undergraduates, particularly first-year and other at-risk students, become scholars. Second, students need to develop adaptive ways of thinking—namely, believing that they are “in control” of their academic performances—to excel in their academic work. We review evidence demonstrating that Attributional Retraining treatments can enhance students’ perceived academic control, which increases their motivation, achievement, and persistence.

In this randomized multicenter study of 136 patients, 6 courses of CHOP (cyclo-phosphamide/doxorubicin/vincristine/prednisone) followed by rituximab (CHOP-R) were compared with rituximab-supplemented high-dose sequential chemotherapy with autografting (R-HDS) to assess the value of intensified chemo-therapy as a first-line treatment for high-risk follicular lymphoma (FL) after the introduction of monoclonal antibodies. The analysis was intention to treat with event-free survival (EFS) as the primary endpoint. Complete remission (CR) was 62% with CHOP-R and 85% with R-HDS (P < .001). At a median follow-up (MFU) of 51 months, the 4-year EFS was 28% and 61%, respectively (P < .001), with no difference in overall survival (OS). Molecular remission (MR) was achieved in 44% of CHOP-R and 80% of R-HDS patients (P < .001), and was the strongest independent outcome predictor. Patients relapsing after CHOP-R underwent salvage R-HDS in 71% of cases. Salvage R-HDS had an 85% CR rate and a 68% 3-year EFS (MFU, 30 months). We conclude that (1) achieving MR is critical for effective disease control, regardless of which treatment is used; (2) R-HDS ensures superior disease control and molecular outcome than CHOP-R, but no OS improvement; and (3) CHOP-R failures have a good outcome after salvage R-HDS, suggesting that relapsed/refractory FL could be the most appropriate setting for R-HDS–like treatments. This trial was registered at www.clinicaltrials.gov as no. NCT00435955.

Objectives The objectives of the present study are to review the technique of endoscopic staple-assisted esophagodiverticulostomy (ESED) for the treatment of Zenker's diverticulum and to describe our e-perience and modifications with ESED and the advantages of ESED over previous treatments of Zenker's diverticulum. Study Design Retrospective review of 74 cases of ESED performed for the treatment of Zenker's diverticulum. Methods Patient's records were retrospectively reviewed and tabulated for age, se-, size of diverticulum, symptoms, duration of symptoms, operative time, length of postoperative hospital stay, oral intake, complications, and relief of symptoms. Results The senior author (r.l.s.) previously reported results in 36 cases of ESED performed in 34 patients with Zenker's diverticulum. We have performed an additional 38 cases of ESED in 37 patients between March 1997 and August 1999. The rate of success of ESED was similar between the two series. The average perioperative time, time until oral intake, and length of postoperative hospital stay decreased in the second series. Overall, there were no mortalities and few complications with ESED. Compared with other forms of treatment of Zenker's diverticulum, such as Dohlman's procedure, diverticulectomy, and diverticulopexy, ESED has a similar rate of success, decreased perioperative time, decreased convalescence, and decreased mortality and complications. Conclusions Cost-effectiveness, safety, and efficacy of ESED offer new advantages over previously used treatments for Zenker's diverticulum. These results continue to support the use of ESED as the initial treatment of choice for patients with Zenker's diverticulum.

(1997). Why So Much Confusion? Debating and Creating Inclusive Schools. The Educational Forum: Vol. 61, No. 3, pp. 240-246.

Stainless steel welding produces fumes that contain carcinogenic metals. Therefore, welders may be at risk for the development of lung cancer, but animal data are inadequate in this regard. Our main objective was to examine lung tumor production and histopathological alterations in lung-tumor-susceptible (A/J) and -resistant C57BL/6J (B6) mice exposed to manual metal arc-stainless steel (MMA-SS) welding fume. Male mice were exposed to vehicle or MMA-SS welding fume (20 mg/kg) by pharyngeal aspiration once per month for 4 mo. At 78 wk postexposure, gross tumor counts and histopathological changes were assessed and metal analysis was done on extrapulmonary tissue (aorta, heart, kidney, and liver). At 78 wk postexposure, gross lung tumor multiplicity and incidence were unremarkable in mice exposed to MMA-SS welding fume. Histopathology revealed that only the exposed A/J mice contained minimal amounts of MMA-SS welding fume in the lung and statistically increased lymphoid infiltrates and alveolar macrophages. A significant increase in tumor multiplicity in the A/J strain was observed at 78 wk. Metal analysis of extrapulmonary tissue showed that only the MMA-SS-exposed A/J mice had elevated levels of Cr, Cu, Mn, and Zn in kidney and Cr in liver. In conclusion, this study further supports that MMA-SS welding fume does not produce a significant tumorigenic response in an animal model, but may induce a chronic lung immune response. In addition, long-term extrapulmonary tissue alterations in metals in the susceptible A/J mouse suggest that the adverse effects of this fume might be cumulative.

Epidemiological studies suggest that welding, a process which generates an aerosol of inhalable gases and metal rich particulates, increases the risk for cardiovascular disease. In this study we analyzed systemic inflammation and atherosclerotic lesions following gas metal arc-stainless steel (GMA-SS) welding fume exposure. Apolipoprotein E knockout (apoE(-/-)) mice, fed a Western diet, were exposed to GMA-SS at 40mg/m(3) for 3h/day for ten days (∼8.26μg daily alveolar deposition). Mice were sacrificed two weeks after exposure and serum chemistry, serum protein profiling and aortic lesion area were determined. There were no significant changes in serum total cholesterol, triglycerides or alanine aminotransferase. Serum levels of uric acid, a potent antioxidant, were decreased perhaps suggesting a reduced capacity to combat systemic oxidative stress. Inflammatory serum proteins interleukin 1 beta (IL-1β) and monocyte chemoattractant protein 3 (MCP-3) were increased two weeks after GMA-SS exposure. Analysis of atherosclerotic plaques showed an increase in lesion area as the result of GMA-SS exposure. In conclusion, GMA-SS exposure showed evidence of systemic inflammation and increased plaque progression in apoE(-/-) mice. These results complement epidemiological and functional human studies that suggest welding may result in adverse cardiovascular effects.

Author(s): Swanson, Patti C Wooten; Schindler, Nancilynne; Tran, Thom T | Abstract: The best time to talk with aging parents about how you can help manage their assets is before any need arises, but for most it will still be a sensitive subject. These publications will help you make a workable plan AND keep communications open.

Author(s): Swanson, Patti C Wooten; Schindler, Nancilynne; Tran, Thom T | Abstract: The best time to talk with aging parents about how you can help manage their assets is before any need arises, but for most it will still be a sensitive subject. These publications will help you make a workable plan AND keep communications open.

Author(s): Swanson, Patti C Wooten; Schindler, Nancilynne; Tran, Thom T | Abstract: The best time to talk with aging parents about how you can help manage their assets is before any need arises, but for most it will still be a sensitive subject. These publications will help you make a workable plan AND keep communications open.

Author(s): Swanson, Patti C Wooten; Schindler, Nancilynne; Tran, Thom T | Abstract: The best time to talk with aging parents about how you can help manage their assets is before any need arises, but for most it will still be a sensitive subject. These publications will help you make a workable plan AND keep communications open.

A patient with dysphagia including symptoms of regurgitation of food and worsening pulmonary symptoms was found to have a lateral pharyngeal pouch. The diagnosis was made by barium swallow study and confirmed by endoscopy. The characteristic barium swallow findings include retention of barium in a sac or diverticulum. Endoscopy showed a pouch in the left lateral pharynx, adjacent to the vallecula. Surgical therapy consisting of endoscopic stapling of the mucosal band separating the pouch from the pharynx was performed successfully, and the patient improved dramatically.

Nanotechnology is an emerging field that demands urgent development of adequate toxicology and risk assessment. The previous experimental data on carbon nanotube respiratory exposure strongly suggest the need for complex evaluation of potential toxicity. Our work demonstrates that after carbon nanotube deposition in the lung, acute local and systemic responses are activated and characterized by a blood gene and protein expression signature. The approach described here will foster the development of biomarkers for application in human screening of nanoparticle exposure.

Background Recent studies suggest low-income women of childbearing age may be at risk of suboptimal folate intake. Objective To evaluate the effect of learner-centered nutrition education on folate intake and food-related behaviors among nonpregnant, low-income women of childbearing age, compared to education unrelated to nutrition. Design Participants were randomly assigned by recruitment site to receive either the nutrition lesson or a control lesson about resource management. Participants Nonpregnant, low-income (≤185% federal poverty level) women of childbearing age (18 to 45 years, n=155) from five California counties. Main outcome variables Changes in folate intake and other food-related behaviors. Statistical analysis Analysis of covariance, adjusting for baseline responses and potential confounders. Results Adjusting for baseline, participants who received the nutrition education had greater increases in folate intake and use of the Nutrition Facts label than the control group. Change in intake of specific folate-rich foods differed by ethnicity. Participants in the Special Supplemental Nutrition Program for Women, Infants, and Children who received the nutrition education increased folate intake but had no significant changes in other food-related behaviors. Food stamp recipients who received the nutrition education had no significant changes in folate intake but did increase the frequency of eating more than one kind of vegetable each day, compared to controls. Conclusions This study supports the use of learner-centered approaches to nutrition education for low-income audiences, compared to education unrelated to nutrition. Future work is needed to compare learner-centered techniques to traditional pedagogical nutrition education, and to determine whether observed changes from this study persist over the long term.

It has been suggested that welding fume (WF) exposure increases lung cancer risk in welders. Epidemiology studies have failed to conclude that WF alone causes lung cancer and animal studies are lacking. We examined the course of inflammation, damage, and repair in the lungs of A/J mice, a lung tumor susceptible strain, caused by stainless steel WF. Mice were exposed by pharyngeal aspiration to 40 mg/kg of WF, silica, or saline. Bronchoalveolar lavage (BAL) was performed 24 hours, 1 and 16 weeks to assess lung injury and inflammation and histopathology was done 1, 8, 16, 24, and 48 weeks postexposure. Both exposures increased inflammatory cells, lactate dehydrogenase and albumin at 24 hr and 1 week. At 16 weeks, these parameters remained elevated in silica-exposed but not WF-exposed mice. Histopathologic evaluation at 1 week indicated that WF induced bronchiolar epithelial hyperplasia with associated cellular atypia, alveolar bronchiolo-alveolar hyperplasia (BAH) in peribronchiolar alveoli, and peribronchiolar lymphogranulomatous inflammation. Persistent changes included foci of histiocytic inflammation, fibrosis, atypical bronchiolar epithelial cells, and bronchiolar BAH. The principle changes in silica-exposed mice were histiocytic and suppurative inflammation, fibrosis, and alveolar BAH. Our findings that WF causes persistent bronchiolar and peribronchiolar epithelial changes, suggest a need for studies of bronchiolar changes after WF exposure.

Objectives: To improve the intraoperative anatomic identification of normal tissues during surgery using histologic-like criteria. Study Design: A contact telescope was used to identify normal visceral tissues in an animal model using pigs and dogs during routine human surgical procedures. Methods: Tissues that could be identified grossly were stained topically with methylene blue and then examined with the contact telescope. The histologic appearance of these tissues with the contact telescope was correlated with routine histologic hematoxylin and eosin stains obtained after such tissues were excised. Results: Normal tissues, such as fat, blood vessels, muscle, and parathyroid tissue, can be identified reliably in animals and humans. The contact telescope appears to be able to differentiate between a variety of visceral tissues in the neck and may become useful for practical differentiation between tissues during surgery.

Pneumoparotid is considered to be a rare entity, but the diagnosis might not be as uncommon as reported. We report a case in which computed tomography incidentally revealed air in the parotid ducts bilaterally. Treatment is aimed at the elimination of predisposing and causative factors, but because our patient denied any symptoms or precipitating factors and had a benign presentation, no immediate intervention was initiated.

While the majority of applications of robotics in the field of rehabilitation focus on the development of smart aids for people without upper extremity function, there is also potential for the robot as a therapy "aide." We designed, built, and pilot-tested hardware and software that used a robot to provide muscle reeducation movement patterns after stroke. This is a report on a field trial, in which 11 occupational therapists used the system with 22 patients; each patient averaged 2.2 sessions. Based on information contained in the system database, a log, patient interviews, and therapist questionnaires, we evaluated safety, system utility, and patient and therapist acceptance. The results suggest that robotic treatment is safe and accepted (if not welcomed) by patients. The therapists expressed a qualified acceptance, suggesting several modifications to increase utility. The potential for the application of robotics in rehabilitation therapy is discussed in light of these findings.

Background Welding fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metal-containing welding fumes and to determine if these fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. We exposed male A/J and C57BL/6J, a lung tumor resistant strain, by pharyngeal aspiration four times (once every 3 days) to 85 μg of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) fume, or to 25.5 μg soluble hexavalent chromium (S-Cr). Shams were exposed to saline vehicle. Bronchoalveolar lavage (BAL) was done at 2, 7, and 28 days post-exposure. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 48 and 78 weeks post-exposure. Results BAL revealed notable strain-dependent differences with regards to the degree and resolution of the inflammatory response after exposure to the fumes. At 48 weeks, carcinogenic metal-containing GMA-SS fume caused the greatest increase in tumor multiplicity and incidence, but this was not different from sham. By 78 weeks, tumor incidence in the GMA-SS group versus sham approached significance (p = 0.057). A significant increase in perivascular/peribronchial lymphoid infiltrates for the GMA-SS group versus sham and an increased persistence of this fume in lung cells compared to the other welding fumes was found. Conclusion The increased persistence of GMA-SS fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain.

Long-term care is an important consider- ation in financial planning for later life by Patti C. Wooten Swanson and Karen P. Varcoe “L ong-term care” refers to a variety of services and supportive mea- sures to meet health or personal care needs over an extended period of time. Most long-term care is nonskilled per- sonal care assistance, such as help with the everyday activities of living. Long-term care can be very expen- sive. A private room in a California nursing home (the most expensive type) averages $239.30 per day or $87,345 per year, and the care recipient must pay for doctor bills, hospitalizations and prescription drugs (Kaiser Commission 2006; Genworth Financial 2010). While not all Californians will need expensive long-term care, 70% of those over age 65 will need some dur- ing their lifetimes. Without advance planning, paying for long-term care could result in sacrificing a lifetime of savings or even losing one’s financial independence (California Healthcare Foundation 2010). Age, gender, marital status and lifestyle choices influence whether or not a person will need long-term care. The older a person gets, the more likely that it will be needed. Regardless of health status, the very old (over age 85) may need assistance with activities of daily living, such as household chores or transportation (Family Caregiver Alliance 2005). Women are more likely than men to need long-term care, and typically for a longer period of time (av- erage 3.7 years) than men (average 2.2 years) (US DHHS 2002). Women 65 or older today have a 44% chance of entering a nursing home at some point, compared with 27% of men (Genworth Financial 2006). A single or widowed elder is more likely to need long-term care than one who has a spouse or partner at home. Lifestyle choices such as smoking, sedentary living and poor nutrition increase the risk of needing long-term care and may result in the need for more extensive services at the end of life. Several factors affect what an indi- vidual actually pays for care. Often, the intensity and duration of care increase over time and may coincide with a pro- gression of care settings from home and community, to assisted living, and in some cases to a nursing home. For ex- ample, an elder might need occasional assistance (once or twice per year for certain activities such as traveling), then periodic assistance (monthly or weekly, for activities such as cleaning and shopping), then daily assistance (with tasks such as preparing meals, bathing and dressing), and finally as- sistance and supervision 24 hours per day. Increasing levels of care are usually more expensive. Homemaker services (shopping, meal preparation, cleaning, etc.) are generally less expensive than home health care, which usually costs less than assisted living. Skilled nursing care is the most expensive. A person’s age when care begins in- fluences how long care will be needed, and thus the lifetime costs. Someone who receives long-term care at age 65 will probably require care for more years than one who begins at age 85. Those who are cognitively impaired, as with Alzheimer’s disease, may need care for longer because the disease af- fects the ability to live independently but doesn’t necessarily shorten life. Costs also depend on where a care re- cipient lives. California has some of the highest costs in the country, and aver- ages about 15% higher in urban than in rural areas (Genworth Financial 2007). The Web site www.medicare.gov has a calculator for estimating one’s poten- tial lifetime care costs. The Long-term Care Planning Tool uses a confidential survey and national usage data to create a customized estimate, suggest types of long-term care services that might be needed and identify possible financing options, including insurance. Another approach is to project the types of care a person may need over a lifetime and how many years for each, then calculate estimated lifetime costs using local cost data. The default planning scenario used by the Federal Long-Term Care Insurance Program (for federal employees) is 5 years: 2 for home health, 1 of assisted living and 2 of nursing home care (table 1). Since most Californians will likely need some type of long-term care as they age, although the type and duration of care will vary, it is important for families to address the issue of long-term care as part of a comprehensive personal financial plan. P.C.W. Swanson is Nutrition, Family and Con- sumer Science Advisor, UC Cooperative Extension (UCCE), San Diego County; and K.P. Varcoe is Consumer Economics Specialist, UC Riverside. Assistance was provided by Nancilynne Schindler and Thom Tran, Staff Research Associates, UCCE San Diego. References California Healthcare Foundation. 2010. Survey: Many Californians Not Ready for Health Care Costs. California- Healthline (April 22):1. Family Caregiver Alliance. 2005. Selected Long-Term Care Statistics. www.caregiver.org (accessed 4/13/06). Genworth Financial. 2006. The Impact of Long Term Care On Women — An Analysis of Women As Care Pro- viders and Care Recipients, Exec Sum: 20. Rep NS40758. Genworth Financial. 2007. Cost of Care Survey, Execu- tive Summary: 10. Pub 37522. Genworth Financial. 2010. Genworth Financial 2010 Cost of Care Survey, California. www.genworth.com. [Kaiser Commission] Kaiser Commission on Medicaid and the Uninsured. 2006. Private Long-term Care In- surance: A Viable Option for Low and Middle Income Seniors? Pub No 7459. Kaiser Family Foundation. Wash- ington, DC. 2 p. [US DHHS] US Department of Health and Human Ser- vices. 2002. National Clearinghouse on Long-Term Care. Own Your Future: Understanding Long-Term Care. www. longtermcare.gov. TABLE 1. Estimate of lifetime total for long-term care received over 5 years in California, 2010 Years Total Source: Genworth Financial 2010; California – State Median: Annual Care Costs in 2010. Type of care Home health care: Medicare-certified & licensed home health aide (50 hours per week) Assisted living (private one-bedroom unit) Nursing home (private room) Annual cost Total cost CALIFORNIA AGRICULTURE • VOLUME 64 , NUMBER 4

A prospective trial conducted in the period 2000-2005 showed no survival advantage for high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (CHOP-R) as first-line therapy in 134 high-risk follicular lymphoma patients aged

PURPOSE We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range, 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard versus experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively ( P = .238). CONCLUSION A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.

Bendamustine is an alkylating agent with a nitrogen mustard group and a purine-like benzimidazole group. The aim of this study was to collect all the Italian experiences with this drug in order to evaluate the results in term of response to therapy and toxicities. We analyzed lymphoma patients treated in 24 Italian haematological centres with bendamustine alone or in combination with anti-CD20 antibody. One hundred seventy-five relapsed or refractory lymphoma patients were enrolled. The median age was 69 years (range 26-87). Seventy-nine patients were relapsed, 35 were refractory and 61 presented a progressive disease after partial response. The diagnoses were 60 indolent non-follicular lymphomas, 34 diffuse large B-cell lymphomas, 48 follicular lymphomas, 30 mantle cell lymphomas and three peripheral T-cell lymphomas. All patients were evaluable for response: 52 (29%) with complete remission, 72 (43%) with partial response with an overall response rate of 71%, and 51 non-responders. With a median observation period of 10 months (1-43), 70% of patients are alive. In summary, this retrospective study shows that treatment with bendamustine alone or in combination with rituximab is a safe and effective regimen in a subset of multi-resistant patients.

To evaluate in a prospective multicenter trial the feasibility and clinical efficacy of the combination of alemtuzumab (Campath-1H) with the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen (CHOP-C) as the primary treatment for patients with peripheral T-cell lymphoma (PTCL), between January 2003 and December 2005, 24 consecutive patients with PTCL entered the study and received 8 CHOP courses. Alemtuzumab was added at 30 mg subcutaneously at day −1 initially to the first 4 courses (4 patients), and then to all 8 courses (20 patients). Complete remission (CR) was achieved in 17 (71%) patients, 1 had partial remission, and 6 had stable/progressive disease. At a median follow-up of 16 months (range, 5-42 months), 14 patients were alive, 9 had died from progressive disease, and 1 had died from pneumonia at day +198 while in CR. So far, 13 are disease-free, with an overall median duration of response of 11 months. The most frequent side effects were grade 4 neutropenia and cytomegalovirus (CMV) reactivation. Major infections were Jacob-Creutzfeldt (J-C) virus reactivation, pulmonary invasive aspergillosis, Staphylococcus sepsis, and pneumonia. This study shows that CHOP-C: (1) is a feasible chemoimmunotherapy regimen; (2) is effective in PTCL with a high rate of CR achievement; and (3) is associated with mostly manageable infectious complications. This clinical trial was registered with the Osservatorio Nazionale sulla Sperimentazione cinica as ID no. 141202.

Purpose A strong prognostic score that enables a stratification of newly diagnosed Hodgkin Lymphoma (HL) to identify patients at high risk of refractory/relapsed disease is still needed. Our aim was to investigate the potential value of a radiomics analysis pipeline from whole-body MRI (WB-MRI) exams for clinical outcome prediction in patients with Hodgkin Lymphoma (HL). Materials and methods Index lesions from baseline WB-MRIs of 40 patients (22 females; mean age 31.7 ± 11.4 years) with newly diagnosed HL treated by ABVD chemotherapy regimen were manually segmented on T1-weighted, STIR, and DWI images for texture analysis feature extraction. A machine learning approach based on the Extra Trees classifier and incorporating clinical variables, 18F-FDG-PET/CT-derived metabolic tumor volume, and WB-MRI radiomics features was tested using cross-validation to predict refractory/relapsed disease. Results Relapsed disease was observed in 10/40 patients (25%), two of whom died due to progression of disease and graft versus host disease, while eight reached the complete remission. In total, 1403 clinical and radiomics features were extracted, of which 11 clinical variables and 171 radiomics parameters from both original and filtered images were selected. The 3 best performing Extra Trees classifier models obtained an equivalent highest mean accuracy of 0.78 and standard deviation of 0.09, with a mean AUC of 0.82 and standard deviation of 0.08. Conclusions Our preliminary results demonstrate that a combined machine learning and texture analysis model to predict refractory/relapsed HL on WB-MRI exams is feasible and may help in the clinical outcome prediction in HL patients.

Imaging of lymphoma is based on the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) and/or contrast-enhanced CT, but concerns have been raised regarding radiation exposure related to imaging scans in patients with cancer, and its association with increased risk of secondary tumors in patients with lymphoma has been established. To date, lymphoproliferative disorders are among the most common indications to perform whole-body magnetic resonance imaging (MRI). Whole-body MRI is superior to contrast-enhanced CT for staging the disease, also being less dependent on histology if compared to 18F-FDG-PET/CT. As well, it does not require exposure to ionizing radiation and could be used for the surveillance of lymphoma. The current role of whole-body MRI in the diagnostic workup in lymphoma is examined in the present review along with the diagnostic performance in staging, response assessment and surveillance of different lymphoma subtypes.

PURPOSE To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613 ), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). CONCLUSION cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.