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1. Site fidelity, population identity and demographic characteristics of humpback whales in the New York Bight apex

Author

Brown, D. M., primary, Robbins, J., additional, Sieswerda, P. L., additional, Ackerman, C., additional, Aschettino, J. M., additional, Barco, S., additional, Boye, T., additional, DiGiovanni, R. A., additional, Durham, K., additional, Engelhaupt, A., additional, Hill, A., additional, Howes, L., additional, Johnson, K. F., additional, Jones, L., additional, King, C. D., additional, Kopelman, A. H., additional, Laurino, M., additional, Lonergan, S., additional, Mallette, S. D., additional, Pepe, M., additional, Ramp, C., additional, Rayfield, K., additional, Rekdahl, M., additional, Rosenbaum, H. C., additional, Schoelkopf, R., additional, Schulte, D., additional, Sears, R., additional, Stepanuk, J. E. F., additional, Tackaberry, J. E., additional, Weinrich, M., additional, Parsons, E. C. M., additional, and Wiedenmann, J., additional

Published
2022
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10. Phase II study of carfilzomib, thalidomide, and low-dose dexamethasone as induction and consolidation in newly diagnosed, transplant eligible patients with multiple myeloma; the Carthadex trial

Author

Wester, R., Holt, B. (Bronno) van der, Asselbergs, E, Zweegman, S. (Sonja), Kersten, M.J. (Marie José), Vellenga, E. (Edo), Kooy, M.V.M., Weerdt, O. (Okke) de, Minnema, M., Lonergan, S, Palumbo, A., Lokhorst, H.M. (Henk), Broyl, A. (Annemiek), Sonneveld, P. (Pieter), Wester, R., Holt, B. (Bronno) van der, Asselbergs, E, Zweegman, S. (Sonja), Kersten, M.J. (Marie José), Vellenga, E. (Edo), Kooy, M.V.M., Weerdt, O. (Okke) de, Minnema, M., Lonergan, S, Palumbo, A., Lokhorst, H.M. (Henk), Broyl, A. (Annemiek), and Sonneveld, P. (Pieter)

Abstract

This is a phase II dose escalation trial of carfilzomib in combination with thalidomide and dexamethasone for induction and consolidation in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The results of four dose levels are reported. Induction therapy consisted of four cycles of carfilzomib 20/27 mg/m2 (n=50), 20/36 mg/m2 (n=20), 20/45 mg/m2 (n=21), and 20/56 mg/m2 (n=20) on days 1, 2, 8, 9, 15, 16 of a 28-day cycle; thalidomide 200 mg on day 1 through 28 and dexamethasone 40 mg weekly. Induction therapy was followed by high-dose melphalan and autologous stem cell transplantation and consolidation therapy with four cycles of carfilzomib, thalidomide and dexamethasone in the same schedule except a lower dose of thalidomide (50 mg). Very good partial response rate or better and complete response rate or better after indu

Published
2019
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11. Book reviews

Author

Lonergan, S. C., Greenberg, M., Krmenec, Andrew J., Malecki, Edward J., Holcomb, B., Stöhr, W. B., Beyers, W. B., Fotheringham, A. S., Knudsen, D. C., Gilbert, G., and Esparza, A.

Published
1990
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12. A phase II study of selinexor(KPT-330) combined with bortezomib and dexamethasone (SVD) for induction and consolidation for patients with progressive or refractory multiple myeloma: The selvedex trial

Author

Broijl, A, Asselbergs, E L, Minnema, M C, Lonergan, S, van der Holt, B, van de Donk, N, Zweegman, S, Sonneveld, P, Hematology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, CCA - Treatment and quality of life, Anatomy and neurosciences, and General practice

Abstract

Selinexor is an oral selective exportin-1 (XPO-1) inhibitor that forces nuclear retention and activation of many tumor suppressor proteins (TSPs) and IkB and is active as monotherapy and combined with dexamethasone in multiple myeloma (MM). Addition of proteasome inhibitors to selinexor increases levels and activity of TSPs/IkB leading to synergistic MM cell death.AimsA dose escalating phase I/II study was performed in patients with progressive and/or refractory MM, evaluating feasibility (phase I) and efficacy (phase II) of selinexor at 3 dose levels combined with twice weekly (BIW) bortezomib and dexamethasone (SVd).MethodsThe maximum tolerated dose (MTD) and recommended dose level (RDL) were determined using a a3+3a dose escalation scheme. Patients could be included if they had received at least one prior anti-myeloma regimen, and were not refractory to bortezomib. Selinexor on days 1,8,15,22, bortezomib 1.3mg/m2 subcutaneously on days 1,4,8,11, dexamethasone 40mg on days 1,8,15,22 in a 28-days schedule.ResultsSeven patients were treated at the first selinexor dose level of 45mg/m2. The median number of prior treatments was 3 (range 2-7). Three patients were lenalidomide refractory during their last treatment. Two patients were deemed ineligible after inclusion, one patient had a transformation to plasma cell leukemia, one was bortezomib refractory. Two out of 5 eligible patients completed treatment as planned. Only one patient completed selinexor at the preplanned dose of 45mg/m2. Reasons for discontinuation were excessive toxicity(n=1), progressive disease(1), other reasons not specified(1). Two patients experienced a DLT, one grade 4 thrombocytopenia with epistaxis, one patient had an ischemic cerebrovascular event. Adverse events (AE) CTC grade 3-4 were observed in all treated patients (table 1). The study continued with a lower dose level of selinexor of 30mg/m2 with adjustment of bortezomib frequency to once weekly on days 4 and 11. The median number of prior treatments was 3 (range 1-7). Three patients were lenalidomide refractory. Two out of 6 patients who started treatment completed treatment as planned. Reasons for discontinuation were neuropathy grade 4(1), pneumonia(1), progressive disease(3). Six patients were treated of whom 4 patients experienced a DLT: hyponatremia grade 3(2), polyneuropathy grade 3(1), syncope grade 3(1).The study was stopped prematurely due to unacceptable toxicity observed in the 2 different dosing schedules of SVd. In the 45mg/m2 group 4 out of 5 (80%) patients achieved aPR, including 2 VGPR, and 1 sCR. Median follow-up (FU) was 27 months (range 0.6-31.5). Median PFS was 17 months, OS at 1 and 2 years was 100% and 75%, respectively. Four out of 6 (67%) patients in the 30mg/m2 group achieved aPR, including 1 VGPR; no CRs were seen. Median FU was 10.1 months (range 0.6-17.9). Median PFS was 10 months, 1 year OS was 75%.ConclusionWe found that both 30 and 45mg/m2 of selinexor in combination with either twice or once weekly bortezomib resulted in unacceptable toxicity. However, in those patients in whom the regimen was feasible we observed remarkable ORR, PFS and OS in this pretreated, predominantly lenalidomide-refractory MM population. This is consistent with results recently presented for once weekly SVd regimens. This regimen, which also showed high ORR and PFS, is currently being evaluated in the international Phase 3 randomized BOSTON study of SVd vs Vd (NCT 03110562).Session topic: 14. Myeloma and other monoclonal gammopathies - ClinicalKeyword(s): bortezomib, Multiple Myeloma, Refractory, TherapyCode of conduct/disclaimer available in General Terms Conditions

Published
2018

16. Impact of Mycoplasma hyopneumoniae and Lawsonia intracellularis on the performance of pigs divergently selected for feed efficiency

Author

Helm, E. T., Outhouse, A. C., Schwartz, K. J., Dekkers, J. C. M., Lonergan, S. M., Rauw , Wendy Mercedes, Gabler, N. K., Helm, E. T., Outhouse, A. C., Schwartz, K. J., Dekkers, J. C. M., Lonergan, S. M., Rauw , Wendy Mercedes, and Gabler, N. K.

Abstract

Feed efficiency (FE) is a valuable trait, yet how genetic selection for enhanced FE affects other processes such as response to disease is unknown. Disease from endemic respiratory and enteric pathogens such as Mycoplasma hyopneumoniae (Mh) and Lawsonia intracellularis (LI) are common in swine production. Therefore, the aim of this study was to examine if pigs selected for high vs. low FE based on residual feed intake (RFI) respond differently to a dual respiratory and enteric challenge. Pigs selected for low RFI (LRFI, high FE) are considered more FE compared to their high RFI (HRFI, low FE) selected counterparts. Using a 2 × 2 factorial design, 25 littermate pairs from the HRFI and 25 littermate pairs from the LRFI line (barrows, 50 ± 7 kg BW) were selected, with one pig from each pair assigned to individual pens in either the challenge or the nonchallenge (control) rooms (n = 25 barrows/line/challenge). On days post inoculation (dpi) 0, the challenged pigs were inoculated with LI and Mh (MhLI). Feed intake, BW, fecal swabs, and serum samples were collected and recorded weekly for 42 d. On dpi −2 and 47, 14 littermate pairs (n = 7 barrows/line/challenge) were utilized for initial and final body composition scans using dual-energy X-ray absorptiometry to calculate longitudinal whole body tissue accretion rates for lean, protein, fat, and bone mineral content. Serum antibody levels and fecal shedding of LI were used to confirm infection. Control pigs remained negative by all measures during the 6-wk trial and MhLI inoculated pigs were confirmed positive via serological antibody responses by dpi 14 for LI and Mh. There were no interactions between RFI line and challenge status for any overall performance parameter (P > 0.05). The 6-wk MhLI challenge resulted in a 17% reduction in ADG, a 12% reduction in ADFI, and a 7% reduction in G:F vs. Controls (P < 0.05). In addition, compared to the Control pigs, MhLI challenge reduced lean, protein, and lipid accretion rates by

Published
2018

17. Effects of heat stress and insulin sensitizers on pig adipose tissue

Author

Seibert, J T, primary, Abuajamieh, M, additional, Sanz Fernandez, M V, additional, Johnson, J S, additional, Kvidera, S K, additional, Horst, E A, additional, Mayorga, E J, additional, Lei, S, additional, Patience, J F, additional, Ross, J W, additional, Rhoads, R P, additional, Johnson, R C, additional, Lonergan, S M, additional, Perfield, J W, additional, and Baumgard, L H, additional

Published
2018
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22. Effects of diet and genetics on growth performance of pigs in response to repeated exposure to heat stress

Author

Rauw , Wendy Mercedes, Mayorga, E. J., Lei, S. M., Dekkers, J. C. M., Patience, J. F., Gabler, N. K., Lonergan, S. M., Baumgard, Lance H., Rauw , Wendy Mercedes, Mayorga, E. J., Lei, S. M., Dekkers, J. C. M., Patience, J. F., Gabler, N. K., Lonergan, S. M., and Baumgard, Lance H.

Abstract

Heat stress (HS) is one of the costliest issues in the U.S. pork industry. Aims of the present study were to determine the consequences of repeated exposure to HS on growth performance, and the effects of a high fiber diet, the genetic potential for high lean tissue accretion, and the genetic potential for residual feed intake (RFI) on resilience to HS. Barrows (n = 97) from three genetic lines (commercial, high RFI, low RFI) where subjected three times to a 4-day HS treatment (HS1, HS2, and HS3) which was preceded by a 9-day neutral (TN) adaptation period (TN1) and alternated by 7-day periods of neutral temperatures (TN2, TN3, and TN4). Body weight gain (BWG), feed intake (FI), feed conversion efficiency (FCE), RFI, and the drop in BWG and FI between TN and HS were estimated for each period, and slaughter traits were measured at the end of TN4. Commercial pigs had lower FI when fed a high fiber diet compared to a regular diet (2.70 ± 0.08 vs. 2.96 ± 0.08 kg/d; P < 0.05), while no differences were found for BWG, RFI or FCE. HS reduced FI, BWG, and FCE, increased RFI, and resulted in leaner pigs that generate smaller carcasses at slaughter. In TN, commercial pigs grew faster than the low and high RFI pigs (1.22 ± 0.06 vs. 0.720 ± 0.05 and 0.657 ± 0.07; P < 0.001) but growth rates were not significantly different between the lines during HS. Growth rates for the low RFI and high RFI pigs were similar both during TN and during HS. Pigs of interest for genetic improvement are those that are able to maintain growth rates during HS. Our results show that response in growth to HS was repeatable over subsequent 4-d HS cycles, which suggests the potential for including this response in the breeding index. The best performing animals during HS are likely those that are not highly superior for growth in TN. © 2017 Rauw, Mayorga, Lei, Dekkers, Patience, Gabler, Lonergan and Baumgard.

Published
2017

39. Selection for lean growth efficiency in Duroc pigs influences pork quality

Author

Lonergan, S. M., Huff-Lonergan, E., Rowe, L. J., Kuhlers, D. L., and Jungst, S. B.

Subjects
Swine -- Genetic aspects, Meat -- Quality, Pork -- Genetic aspects, Zoology and wildlife conservation
Abstract

A unique line of Duroc pigs was established by intensive selection for increased lean growth efficiency. The objective of this study was to determine the influence of this selection strategy on fresh pork quality traits. Two lines of Duroc pigs originating from the same foundation herd were evaluated. One line was selected for lean growth efficiency over five generations (Select line), and the other was a contemporary line maintained from the foundation herd (Control line). All pigs in the trial tested negative for the halothane gene. Selection for lean growth efficiency resulted in improved lean gain, carcass lean, increased loin eye area, and less overall carcass fat. The Select line had significantly lower subjective firmness scores in longissimus and significantly greater amounts of moisture and protein lost as measurable drip in longissimus, semimembranosus, and semitendinosus. There were no differences in subjective color scores or in Hunter L, a, and b values between lines. No selection line differences were observed in glycolytic potential or ultimate pH. The longissimus and the semitendinosus exhibited significantly lower early postmortem pH values in Select line pigs. Warner-Bratzler shear values were higher for Select line longissimus chops. Degradation of troponin-T was decreased in the Select line longissimus samples. This result suggests that reduced degradation of myofibrillar proteins may be associated with increased moisture and protein lost during storage. This research points out that elimination of the halothane gene will solve some but not all of the genetically influenced pork quality problems faced by the industry. The Select line of pigs appears to be more prone to producing pork that is soft and exudative, indicating a link between soft and exudative pork and some genetic selection strategies may exist. Therefore, it appears that selection for some economically important traits, such as feed efficiency or increased lean growth in the absence of the halothane gene, may compromise pork quality. Key Words: Meat Quality, Pork, Selection, Tenderness, Water Holding Capacity

Published
2001

40. Antioxidant status affects color stability and tenderness of calcium chloride-injected beef

Author

Harris, S. E., Huff-Lonergan, E., Lonergan, S. M., Jones, W. R., and Rankins, D.

Subjects
Beef cattle -- Food and nutrition, Antioxidants -- Research, Calcium chloride -- Research, Meat -- Quality, Vitamin E -- Research, Beef -- Sensory evaluation, Zoology and wildlife conservation
Abstract

The objectives of this study were to determine whether vitamin E supplementation influences color and tenderness of beef injected with calcium chloride. Market heifers (n = 12) were fed a standard finishing diet with minimal levels of vitamin E (NE group). Another 12 market heifers were fed the NE diet with the inclusion of 1,000 IU/d of DL-[Alpha]-tocopherol per animal for the last 125 d on feed (E group). Animals were slaughtered after 125 d on the diets and upon reaching an ultrasound backfat thickness [is greater than] 10 mm. Half of the longissimus muscles from each treatment group (NE and E) were pumped to 10% over the original weight with 250 mM Ca[Cl.sub.2] (Ca) at 24 h postmortem. Remaining muscles (NE and E) were pumped to 10% over the original weight with water (NC) at 24 h postmortem. After equilibrating overnight, steaks (2.54 cm) were overwrapped with [O.sub.2]-permeable film and stored for 7 d after injection. Hunter 'L,' 'a,' and 'b' values were obtained each day of storage. Trained panelists evaluated color on d 1, 4, and 7 after injection. 2-Thiobarbituric acid-reactive substances (TBARS) values were measured on d 1 and 7 after injection. Warner-Bratzler (W-B) shear force values and trained sensory panel evaluations at 1, 3, and 7 d after injection were obtained. Immunoblotting techniques were used to monitor the 30-kDa degradation product of troponin-T at 1, 3, and 7 d after injection. At 4 d after injection, E/Ca steaks were the least discolored (P [is less than] 0.05). The E/Ca steak TBARS values were not significantly different from values for NE/NC steaks at 7 d after injection, whereas NE/Ca steaks had greater (P [is less than] 0.05) TBARS values after 7 d following injection compared with all other groups. Treatment with Ca resulted in higher off-flavor scores (P [is less than] 0.05). The E/Ca samples had the most rapid tenderization and proteolysis of all treatment groups. Warner-Bratzler shear values were lower in the E/Ca samples than in the E/NC samples at 1, 3, and 7 d after injection (P [is less than] 0.05). No difference in shear force was noted between NE/Ca and NE/NC samples at any time point. No difference in sensory tenderness was noted between NE/Ca and NE/NC samples at 1 d after injection. However, Ca-injected samples (NE/Ca and E/Ca) were rated as being significantly more tender than their uninjected counterparts (NE/NC and E/NC) at 3 and 7 d after injection. Injection of Ca[Cl.sub.2] may result in more rapid and immediate tenderization if beef from animals supplemented with vitamin E is used. Vitamin E incorporation into muscle tissue may potentiate the action of exogenously added calcium by protecting the calpains from oxidation. Key Words: Beef Quality, Calcium Chloride, Meat Characteristics, Vitamin E

Published
2001

47. Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma

Author

Sonneveld, P. (Pieter), Asselbergs, E. (Emilie), Zweegman, S. (Sonja), Holt, B. (Bronno) van der, Kersten, M.J. (Marie José), Vellenga, E. (Edo), Marwijk Kooy, M. (Marinus) van, Broyl, A. (Annemiek), Weerdt, O. (Okke) de, Lonergan, S. (Sarah), Palumbo, A. (Antonio), Lokhorst, H.M. (Henk), Sonneveld, P. (Pieter), Asselbergs, E. (Emilie), Zweegman, S. (Sonja), Holt, B. (Bronno) van der, Kersten, M.J. (Marie José), Vellenga, E. (Edo), Marwijk Kooy, M. (Marinus) van, Broyl, A. (Annemiek), Weerdt, O. (Okke) de, Lonergan, S. (Sarah), Palumbo, A. (Antonio), and Lokhorst, H.M. (Henk)

Abstract

This multicenter phase 2 study of the European Myeloma Network investigated the combination of carfilzomib, thalidomide, and dexamethasone (KTd) as induction/consolidation therapy for transplant-eligible patients with previously untreated multiple myeloma (N = 91). DuringKTdinductiontherapy, patients received 4 cycles of carfilzomib20/27mg/m2 (n = 50), 20/36mg/m2 (n = 20), 20/45 mg/m2 (n = 21),or 20/56mg/m2 (n = 20) on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle; thalidomide 200mg on days 1 to 28; and dexamethasone 20mg on days 1, 2, 8, 9, 15, and 16. After autologous stemcell transplantation, patients proceeded toKTdconsolidation therapy,where the target doses of carfilzomib were 27mg/m2, 36mg/m2, 45 mg/m2, or 56 mg/m2, respectively, and thalidomide 50 mg. Common grade 3/4 adverse events included respiratory (15%), gastrointestinal (12%), and skin disorders (10%); polyneuropathy was infrequent (1%). Complete response rates after induction and consolidation treatment were 25% and 63%, respectively; rates of very good partial response or better after induction and consolidation were 68% and 89%, respectively. At a median follow-up of 23 months, the 36-month progression-free survival rate was 72%. The KTd induction and consolidation regimens were active, safe, and well tolerated. This study was registered at http://www.trialregister.nl as #NTR2422.

Published
2015
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49. Adenoid Reservoir for Pathogenic Biofilm Bacteria

Author

Nistico, L., Kreft, R., Gieseke, A., Coticchia, J., Burrows, A., Khampang, P., Liu, Y., Kerschner, J., Post, J., Lonergan, S., Sampath, R., Hu, F., Ehrlich, G., Stoodley, P., and Hall-Stoodley, L.

Abstract

Biofilms of pathogenic bacteria are present on the middle ear mucosa of children with chronic otitis media (COM) and may contribute to the persistence of pathogens and the recalcitrance of COM to antibiotic treatment. Controlled studies indicate that adenoidectomy is effective in the treatment of COM, suggesting that the adenoids may act as a reservoir for COM pathogens. To investigate the bacterial community in the adenoid, samples were obtained from 35 children undergoing adenoidectomy for chronic OM or obstructive sleep apnea. We used a novel, culture-independent molecular diagnostic methodology, followed by confocal microscopy, to investigate the in situ distribution and organization of pathogens in the adenoids to determine whether pathogenic bacteria exhibited criteria characteristic of biofilms. The Ibis T5000 Universal Biosensor System was used to interrogate the extent of the microbial diversity within adenoid biopsy specimens. Using a suite of 16 broad-range bacterial primers, we demonstrated that adenoids from both diagnostic groups were colonized with polymicrobial biofilms. Haemophilus influenzae was present in more adenoids from the COM group (P = 0.005), but there was no significant difference between the two patient groups for Streptococcus pneumoniae or Staphylococcus aureus. Fluorescence in situ hybridization, lectin binding, and the use of antibodies specific for host epithelial cells demonstrated that pathogens were aggregated, surrounded by a carbohydrate matrix, and localized on and within the epithelial cell surface, which is consistent with criteria for bacterial biofilms.

Published
2011

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