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International development and aid are often conducted through the allocation of funding determined by decisions of non-locals, especially in the west for those in the global south. In addition, such funding is often disassociated from local expertise, therefore providing little long-term developmental impact and generating distrust. This is particularly true for conservation, as well as environmental and educational programmes. We hypothesize that by granting local people the educational tools and the necessary funding to develop their own projects through the use of an applicant-driven peer-review approach, it is possible to relocalize the decision-making process to the programme participants, with the potential to generate and select more relevant projects with developmental outcomes of higher quality. Here we created an online curriculum for antimicrobial resistance (AMR) education that was followed by 89 participants across Ghana, Tanzania, Nigeria and Uganda. We then created an open research programme that facilitated the creation of eight de novo projects on AMR. Finally, we organized an applicant-driven grant round to allocate funding to the ‘Neonatal Sepsis in Nigeria’ project to conduct a pilot study and awareness campaign. This work opens perspectives for the design of frugal educational programmes and the funding of context-specific, community-driven projects aimed at empowering local stakeholders in the global South.

The taxonomy and lectotypification of Lepidagathis barberi, a steno-endemic species of Tamil Nadu, are discussed in detail here along with colour photograph of habit and close-up of a flowering-twig and a digital image of lectotype specimen.

T-cell prolymphocytic leukemia, or T-PLL, is an extremely rare and highly metastatic neoplasm characterized by proliferating mature T-cells and genetic aberrations that often involve chromosome 14. While T-PLL is commonly accompanied by a complex karyotype, there is little analysis on such cases in existing literature and thorough discussions of the less "characteristic" cytogenetic mutations are particularly lacking. We present a case study of a 68-year-old male T-PLL patient with marked leukocytosis and a history of T-cell lymphoproliferative disorder. Chromosomal analysis revealed a complex karyotype that included a translocation of both copies of chromosome 14, rearrangements on 9p and 5p, isochromosome 8, deletion 11q, and monosomy 17. Molecular cytogenetic analysis indicated a rearrangement of TRD (14q11.2), loss of the ATM and CDKN2A signals, and gains of the RELN, TES and MYC signals. Many of these mutations have strongly corresponded to poor prognoses in patients with T-PLL and other leukemias, especially when appearing concurrently. However, there are still profound knowledge gaps in our understanding of many genetic aberrations and the significance of marker chromosomes in the context of T-PLL. Considering the lack of consensus on the improvement of patient outcomes in the past two decades as well as the frequency of a complex karyotype in T-PLL, this case study highlights the critical need of continued research efforts in profiling complex cases to provide potential avenues for novel therapeutic targets for T-PLL patients.

Ring chromosomes are uncommon in hematological diseases. Here we present the case of a 13-year-old girl with leukocytosis, anemia, and lymphadenopathy. Flow cytometry analysis revealed a predominant precursor T lymphoid population expressing CD7, CD5, CD2, and cytoplasmic CD3 with partial expression of CD33, CD34, CD117, and CD11c; TdT was positive, and myeloperoxidase was negative. The bone marrow aspirate showed markedly increased blasts that were positive for CD3, CD7, CD34, TdT, and myeloperoxidase (rare positivity) by immunohistochemistry stain, consistent with T-cell acute lymphoblastic leukemia (T-ALL) extensively involving a hypercellular marrow for age. The karyotype showed a ring 7 in 12 of the 21 metaphase cells examined and deletions of the subtelomeric regions on chromosome 7. Deletions in the short arm of chromosome 7 and the long arm of chromosome 7 are present in 2% to 4% of pediatric T-ALL cases. Ring chromosome 7 is typically seen in myeloid malignancies, including acute myeloid leukemia.

Myelodysplastic syndromes present with a range of cytogenetic abnormalities that are used to guide diagnosis and management of the disease. Herein, we present the case of a 72-year-old female patient who presented with pancytopenia. Peripheral blood showed Hb 9.0 g/dl, neutrophils less than 1800/mm3, and platelets less than 100,000/mm3. Bone marrow showed erythroid hyperplasia, megaloblastic changes, dyserythropoiesis, multinuclearity, nuclear bridges, nuclear budding, atypical mitoses, and ring sideroblasts. Also, CD34 and CD117 as well as myeloperoxidase positive populations were present. On this basis, a diagnosis of myelodysplastic syndrome was rendered. Chromosome studies showed an abnormal female karyotype with an isochromosome 17q as well as deletion 20q in 17 of the 20 metaphase cells examined. The remaining three cells were cytogenetically normal. Molecular cytogenetic studies using a TP53-specific probe showed only one TP53 signal in 87% of the nuclei examined. An i(17q) as a sole cytogenetic aberration is rare among both MDS and myeloid malignancies in general, but is functionally similar to aberrations of 17p that lead to loss of TP53. This case provides further insight into the spectrum of cytogenetic abnormalities present in MDS.

Staphylococcal scalded skin syndrome (SSSS) and toxic epidermal necrolysis (TEN) are dermatologic conditions that have a similar clinical appearance. Careful attention to clinical features, such as the coloration at the base of the blister, and histopathology are utilized to make an accurate diagnosis. While supportive therapy is required for both conditions, SSSS requires appropriate antibiotics to treat the underlying staphylococcus and TEN requires elimination of an offending drug (usually an antibiotic).

Context.— Large B-cell lymphomas represent the most common non-Hodgkin lymphomas and often present as extranodal masses with advanced stage similar to metastatic tumors. Without proper intraoperative, microscopic, immunophenotypic, and cytogenetic evaluation they may be mistaken for other hematopoietic or even nonhematopoietic tumors. Also, diffuse large B-cell lymphomas often have clinical, morphologic, immunophenotypic, and cytogenetic clinical features that are similar to those of other less common B-cell lymphomas. Furthermore, classification of these neoplasms is continually becoming more refined. Objective.— To provide a rational, methodic approach to the evaluation of large B-cell lymphomas for community practice pathologists who provide general pathology services. Data Sources.— This review incorporates guidelines detailed in the 2017 update to the World Health Organization's Classification of Tumours of Haematopoietic and Lymphoid Tissues in addition to other recent peer-reviewed publications. Conclusions.— Many large B-cell neoplasms respond favorably to current treatments, but these cases also require accurate and timely diagnoses. We propose a process following a brief checklist that focuses on diffuse large B-cell lymphoma, the most common entity, and rules out other similar lymphomas in a stepwise fashion.

A 6-year-old otherwise healthy female presented to the ED with a right eyebrow lesion for one month. Previous I&D attempts and empiric antibiotic treatment had failed to improve the lesion. Following dermatology referral, superficial culture resulted with growth of Cryptococcus neoformans after which completion of oral fluconazole treatment resolved the lesion. Though Cryptococcus neoformans infections commonly plague immunocompromised patients, primary cutaneous cryptococcosis in the immunocompetent patient is a rare but documented infection with a paucity of reported pediatric cases, and frontline physicians should be aware of such a diagnosis in the setting of persistent skin lesions without response to more commonly utilized therapies.

Verrucous sarcoidosis (VS) is a rare variant of cutaneous sarcoidosis that most often appears on the lower extremities. It could represent a localized hypertrophic response over an area with underlying noncaseating sarcoidal granulomas or a response secondary to a viral wart overlying a sarcoidal plaque. A case of annular VS on the face is reported in the setting of widespread background cutaneous papular and plaque sarcoidosis.

The declining trend of the population of certain marine organisms may be due to lack of management where juveniles are being caught and grown out. In the Philippines, among the marine species affected by this practice is the Plectropomus leopardus, locally known as Lapu-Lapu. Identifying the factors that contribute to the persistence of Lapu-Lapu would be a great help in the thrust of protecting threatened species in the Philippines. Niche Modeling has been widely used in determining the distributions of species and its suitable habitat based on the environmental conditions in which species populations could be maintained. Thus, modeling techniques that require presence-only data such as Maximum Entropy Models (Maxent) have been widely used to predict habitat distributions. This system aims to predict the current and future potential population distribution of the Lapu-Lapu species, using Maxent modelling. PiLNiMo is an application designed to predict the population distribution of Plectropomus leopardus based on the mean sea level pressure, mean temperature, and thunderstorm occurrence.

We investigate non-sequential designs for estimating model parameters in a power logistic model when the power is assumed to be approximately known and only the ranges for the other two parameters are available. The sensitivity of these designs to nominal values of all the three parameters are studied and our proposed optimal designs are shown to be reasonably robust under moderate deviation from the assumed model. An application to a toxicity experiment involving adult beetles is discussed, including the benefits of using an optimal design.

Background: Inflammation mediators, such as NF-kappa B (NFκB) and tumor necrosis factor alpha (TNFα), play major role in breast cancer pathogenesis, progression, and relapse. Triple negative breast cancer (TNBC) is a heterogeneous group of aggressive breast cancers and often has a poor outcome, in which Notch pathways are highly activated. However, role of crosstalk between Notch and inflammation mediators in TNBC progression and recurrence is poorly understood. The present study determines: 1) whether NFκB is highly activated in TNBC cells such as MDA-MB-231 (claudin-low-like) and MDA-MB-468 (basal-like), compared to ER-positive cells (MCF-7); 2) whether TNFα, IL-6 and IL-8 are highly expressed in TNBC cells, compared to MCF-7 cells; 3) whether Notch inhibition by gamma-secretase inhibitors (GSIs) significantly decrease NFκB activation and the expression of TNFα, IL-6 and IL-8 in TNBC cells; 4) whether GSI inhibits TNBC cell migration. Material and Methods: MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. The cells were exposed to GSIs such as DAPT and RO4929097 for 18 hours. Nuclear NFκB activation was determined by using the TransAM NFκB p65 kit (Active Motif). The expressions of TNFα, IL-6, IL-8, and IFNγ were determined by the ELISA kits (R&D Systems). Migration was determined using BD BioCoat Matrigel Invasion Chamber (BD Bioscience Discovery Labware, Sedford, MA). Results: Nuclear NFκB p65 activations (A450) were 0.292±0.015, 0.222±0.005, and 0.132±0.004 in cultured MDA-MB-231, MDA-MB-468, and MCF-7 cells, respectively, in which the negative control was 0.125±0.008 and the difference between the groups were significant (P < 0.01, n=6). TNFα protein level was 266±14 pg/mg in MDA-MB-468 cells, but it was not detected in MCF-7 and MDA-MB-231 cells. IL-8 protein levels were 42.8±3, 30.3±2, and 0.23±0.01 ng/mg in MDA-MB-468, MDA-MB-231, and MCF-7 cells, respectively (P < 0.01 between groups, n=6). IL-6 protein levels were 17.1±0.9, 13.9±0.7, and 0.11±0.02 ng/mg in MDA-MB-468, MDA-MB-231, and MCF-7 cells, respectively (P < 0.01 between groups, n=6). IFNγ was not detected in these three cell lines. DAPT (20 µmol/L) or RO4929097 (10 µmol/L) caused 47.7% or 30.6% reduction in NFκB activation, 34.6% or 32.1% reduction in TNFα expression, and 22.2% or 16.4% reduction in IL-8 expression in MDA-MB-468 cells, compared to DMSO group (P < 0.01, n=6). GSIs had no effect on IL-6 expression. DAPT (20 µmol/L) significantly reduced migration of MDA-MB-468 cells by 23%, compared to DMSO group (P < 0.01, n=6). Discussion: The novel findings are 1) NFκB is highly activated in TNBC cells, compared to ER-positive cells, which is associated with significantly increased the expression of inflammation mediators such as IL-6 and IL-8 in TNBC cells and TNFα in MDA-MB-468; and 2) Notch inhibition by GSIs significantly decrease NFκB activation and the expression of TNFα, and IL-8 in TNBC cells. These results support the hypothesis that the crosstalk between Notch and NFκB lead to activation of inflammation mediators such as TNFα and IL 8, which contribute to TNBC progression and recurrence. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-06-04.

There is considerable research asserting the importance of exploratory search versus exploitative search, however relatively little work examines strategies used to achieve exploratory search. How do individuals and firms explore uncharted technological terrain? This paper extends research on knowledge networks, cognition, and learning to propose three main strategies of knowledge creation that are more likely to result in discoveries that are distant from existing inventions: Deduction, synthetic recombination, and long search paths. We test our arguments using a large and unique dataset on outlier patents filed at the US Patent and Trademark Office. Our findings suggest that there are significant differences in the inventor teams, assignees, and search strategies that result in outlier patents. These results have important implications for managers that wish to encourage more exploratory search for breakthrough innovation.

The diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging, a weak staging system due to different genetic and epigenetic backgrounds. Biological markers improve early detection and guide clinicians in subsequent therapies. Stemness molecules have the potential to identify patients at high risk of developing aggressive cancers. Herein, Zinc finger E-box binding homeobox 1 (ZEB1), Trefoil factor 3 (TFF3), Hepatoma Up-Regulate Protein (HURP), Mucin 2 (MUC2), and Cystic fibrosis transmembrane regulator (CFTR) are assessed as potential prognostic biomarkers in CRC. There were a total of (N=56) cases included in this study which were assessed by a pathologist, out of them 32 were African Americans (AA) and 24 Caucasian Americans (CA). The median follow-up for 42 surviving patients were noted to be 4.5 years (range 2.5 - 7.5 years). A tissue tumor microarray (TMA) was created using tumor stage-matched CRC tissues from AA and CA. The TMA was stained with each biomarker using immunohistochemistry (IHC) and consisted of 132 cores including both controls and tumors. The individual staining score ranged from (0-3) for both area and intensity. The product of area and intensity was used as the final score which ranged from (0-9) with 0 defining no expression and 9 as high expression. We evaluated the association for expression of all the five biomarkers with disease-free survival (DFS) in AA and CA separately. Stratification of the cohort by race revealed that in CA, high ZEB1 expression (nuclear and cytoplasmic) was associated with poor DFS (p= 0.015 for cytoplasm, p= 0.116 for nucleus). ZEB1 expression was not found to be a significant predictor of DFS in AA who are usually known to have worse CRC outcomes. These findings suggest that expression of ZEB1 may represent a marker for CRC prognosis, particularly in CA. High nuclear TFF3 expression in AA was found to be marginally associated with poorer DFS (p=0.089). However, the cytoplasmic expression of TFF3 was not significantly associated with DFS. Both the cytoplasmic and nuclear expression of HURP, MUC2, and CFTR among the AA and CA did not significantly correlate with DFS. Overall, we have identified two stemness molecules, ZEB1 and TFF3, with potential as markers for aggressiveness in CRC. Our findings also provide evidence of a possible biological basis for ethnicity-related differences with regards to stemness and regulatory factors of CRC aggressiveness. ZEB1 can contribute to be a novel biomarker to predict the prognosis of CRC in CA, and TFF3 will be a prognostic marker for AA. Future goals include collecting additional samples and follow-up of the patients to accurately estimate the prognosis. In addition, we will expand the project to the cellular and molecular basis underlining our findings. Funding sources: PCRP W81XWH-14-1-0151, UMMC Medical Student Research Program, and UMMC Office of Research. Citation Format: Ingrid C. Espinoza, Amit Reddy, Xu Zhang, Eldrin Bhanat, Logan Fair, Joy King, Elizabeth Tarsi, Tara Craft, Jesus Monico, Charulochana Subramony, Xinchun Zhou, Roy Duhe, Christopher Lahr, Christian Gomez. Stemness markers in colorectal cancer: Analysis in a racially-diverse population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4716. doi:10.1158/1538-7445.AM2017-4716

Esophageal variceal hemorrhage (EVH) is a serious and expensive sequela of chronic liver disease, leading to increased utilization of resources. Today, endoscopic sclerotherapy (ES) and endoscopic ligation (EL) are the accepted, community standards of endoscopic treatment of patients with EVH. However, there are no published studies comparing the economic costs of treating EVH using these interventions. As part of a prospective, randomized trial comparing ES and EL for the treatment of EVH, we estimated the direct costs of health care utilization and cost-effectiveness for the prevention of variceal rebleeding and patient survival at 1-year follow-up. Treatment groups were similar in incidence of variceal rebleeding (41.9% vs. 42.9%), variceal obliteration (41.9% vs. 40.0%), hospital days, blood transfusions, shunt requirements, and survival (71.0% vs. 60.0%). There were significantly more treatment failures for active bleeding using EL (42% vs. 0%; P = .027) and esophageal stricture formation in the ES-treated patients (19.4% vs. 2.9%; P = 0.03). Median total direct cost outcomes were similar between groups (EL = $9,696 and ES = $13,197; P = .46). EL and ES had similar cost/variceal rebleeding prevented ($28,678 vs. $29,093) and cost/survival ($27,313 vs. $23,804). In the subgroup of active bleeders, ES had a substantially lower cost/survival ($28,523 vs. $51,696). We conclude that resource utilization was similar between treatment groups and that the choice of endoscopic therapy for EVH must still rely on clinical grounds. Further studies comparing costs and resource utilization in this patient population are needed.

We construct optimal designs for heteroscedastic models when the goal is to make efficient prediction over a compact interval. It is assumed that the point or points which are interesting to predict are not known before the experiment is run. Two minimax strategies for minimizing the maximum fitted variance and maximum predictive variance across the interval of interest are proposed and, optimal designs are found and compared. An algorithm for generating these designs is included.

This comment examines the current mechanism for analyzing the issue of whether same-sex marriages celebrated in another jurisdiction will be recognized in Texas and suggests several areas the Texas Legislature should review to give certainty and consistency to any such decision. Part I reviews the Hawaiian case of Baehr v. Lewin and other cases challenging opposite-sex marriage statutes, and outlines the public policy reasons historically offered to avoid recognizing same-sex unions. Part II examines the Texas choice-of-law doctrine as it relates to validity of marriages contracted in other states, and discusses Texas public policy regarding same-sex unions and whether Texas state law mandates recognition of a same-sex marriage validly contracted in another state if the couple is domiciled in Texas. Last, Part III briefly reviews the Full Faith and Credit Clause and the Due Process Clause of the federal Constitution, and discusses whether these principles should compel Texas to recognize same-sex marriages legally contracted in Hawaii or another jurisdiction.

The current diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging. This classification system has weaknesses due to different genetic and epigenetic backgrounds. Biological markers would improve early detection and guide clinicians in subsequent treatment decisions. Stem-like molecules have the potential to identify patients at high risk of developing aggressive carcinomas. Herein, Hepatoma Up-Regulate Protein (HURP) and Zinc finger E-box binding homeobox 1 (ZEB1) are assessed as potential prognostic biomarkers in CRC. Tumors (N = 21) obtained from colectomies and 5 μm formalin-fixed paraffin-embedded blocks were sectioned and immunostained for HURP and ZEB1. For certain cases (N = 8), flash frozen tissues from tumor and adjacent normal colonic tissue were used to extract total RNA, synthesize cDNA, and perform RT-PCR. Presence of tumor cells in analyzed tissue sections was assessed by a pathologist. HURP mRNA expression was 4-fold higher (p = 0.0005) in tumor tissue relative to adjacent normal tissue. Furthermore, an increase in HURP expression was evident in all tumor samples relative to their respective normal tissue control with an average 3-fold increase (p = 0.001). Immunohistochemical analysis (IHC) of HURP revealed expression in all analyzed specimens. Although the stroma was weakly stained for HURP in some cases, all tumors were immunostained for this protein (average intensity score = ++, p Citation Format: Logan Fair, Ingrid Espinoza, Xu Zhang, Abdelouahid Elkhattouti, Tangeng Ma, Joy King, Elizabeth Tarsi, Richard Whitlock, Vijay Kannuthurai, Ryan Jimenez, Tara Craft, Mary Graichen, Sharon Lobert, Roy Duhe, Charulochana Subramony, Christopher Lahr, Christian R. Gomez. Emerging prognostic biomarkers in colorectal cancer: HURP and ZEB1. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4918.

The current clinicopathologic diagnosis of colorectal cancer (CRC) is based on tumor-node-metastasis staging. This classification system has weaknesses due to the different genetic and epigenetic backgrounds not currently incorporated into CRC staging which can ultimately lead to treatment failure. Biological markers would improve early detection and guide clinicians in subsequent treatment decisions. Recently, we and others have identified “stem-like” molecules with the potential to identify patients at high risk of developing aggressive carcinomas. Herein, Hepatoma Up-Regulate Protein (HURP) and Zinc finger E-box binding homeobox 1 (ZEB1) are assessed as potential prognostic biomarkers in CRC. Tumors (N=21) obtained from colectomies and 5 µm formalin-fixed paraffin-embedded blocks were sectioned and immunostained for HURP and ZEB1. For certain cases (N=8), flash frozen tissues from tumor and adjacent normal colonic tissue were used to extract total RNA, synthesize cDNA, and perform RT-PCR. Presence of tumor cells in analyzed tissue sections was assessed by a pathologist. HURP mRNA expression was 4-fold higher (p=0.0005) in tumor tissue relative to adjacent normal tissue. Furthermore, an increase in HURP expression was evident in all tumor samples relative to their respective normal tissue control with an average 3-fold increase (p=0.001). Immunohistochemical analysis (IHC) of HURP revealed expression in all analyzed specimens. Although the stroma was weakly stained for HURP in some cases, all tumors were immunostained for this protein (average intensity score = ++, p Citation Format: Logan Fair, Ingrid Espinoza, Xu Zhang, Abdelouahid Elkhattouti, Tangeng Ma, Joy King, Elizabeth Tarsi, Richard Whitlock, Vijay Kannuthurai, Ryan Jimenez, Tara Craft, Mary Graichen, Sharon Lobert, Roy Duhe, Charulochana Subramony, Christian R. Gomez, Christopher Lahr. HURP and ZEB1: Novel prognostic biomarkers in colorectal carcinomas. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B03.

Color consciousness occurs when individuals identify and respond to the varied skin tones of others. Specifically, African American issues of color consciousness are rooted in the oppression and enslavement of the first Africans forcibly transported to America. As African Americans moved from the plantations to cities and towns, a color-based caste system followed. This caste system assisted in the establishment of an African American middle class with a disproportionate number of lighter-skinned African Americans. The findings regarding the salience of socioeconomic factors, though not conclusive, point to the continued significance of avoiding the trivialization of skin tone as a stimulus characteristic in Black-White interactions.

Summary. We propose an algorithm for constructing minimax D-optimal designs for the logistic model when only the ranges of the values for both parameters are assumed known. Properties of these designs are studied and compared with optimal Bayesian designs and Sitter's (1992, Biometrics, 48, 1145–1155) minimax D-optimal kk-designs. Examples of minimax D-optimal designs are presented for the logistic and power logistic models, including a dose-response design for rheumatoid arthritis patients.

One hundred and eighteen HIV-infected homosexual men without AIDS and 40 control seronegative homosexual men were assessed for 23 parameters reflecting immune activation to determine prognostic significance for occurrence of AIDS. Samples cryopreserved in 1987-1989 were analyzed, with AIDS occurrence determined by mid-1992. Cell surface antigens assessed on the major lymphocyte subsets were HLA-DR, CD38, CD71, and CD25. Soluble serum molecules assessed were tumor necrosis factor alpha, soluble TNFalpha receptor II, soluble IL-2 receptor alpha, neopterin, and beta2-microglobulin. Using a proportional hazards model, prognostic markers included decreased CD4 number and percentage; increased sIL-2R, neopterin, and beta2M; increased percentage HLA-DR+ total lymphocytes and CD4+ cells; increased CD38+ total lymphocytes and CD8+ cells; increased CD71+ total lymphocytes and CD4+ cells; and decreased CD25+ total lymphocytes and CD19+ cells. After adjustment for CD4 cell levels, sIL-2R, neopterin, beta2M, and CD25+ CD19 cells remained significant, indicating that additional information about AIDS risk was provided by these markers.

Objective: We report the clinical outcomes and direct medical costs of 155 patients with severe peptic ulcer hemorrhage and a nonbleeding visible vessel at emergency endoscopy treated with endoscopic hemostasis or medical-surgical therapy. Methods: In two consecutive, prospective, randomized, controlled trials, patients were randomly assigned to endoscopic hemostasis (heater probe, bipolar electrocoagulation, or injection sclerosis) or medical-surgical treatment. Study endpoints included the incidence of severe ulcer rebleeding and emergency surgery, length of hospital stay, blood transfusion requirements, mortality rate, and direct costs of utilized health care. Direct medical costs were estimated using combined fixed and variable institutional costs for consumed resources and Medicare reimbursement rates. Results: Compared with medical-surgical treatment, endoscopically treated patients had significantly lower rates of severe ulcer rebleeding (p = 0.004), emergency surgery (p = 0.002 and p = 0.019, 0.024), and blood transfusions (p = 0.025). Observed inter-trial differences in ulcer rebleeding rates may be partially explained in a multivariate model by covariates of comorbid disease and inpatient ulcer bleeding. In both trials, length of hospital stay, mortality rates, and treatment-related complications were similar. Estimated median direct costs per patient differed: The first trial had lower costs with endoscopic hemostasis ($4254, vs $4620 for electrocoagulation and $5909 for medical-surgical treatment), yet the second trial yielded lower costs with medical-surgical treatment ($3169, vs $3477 for injection sclerosis and $4098 for heater probe). Conclusions: Compared with medical-surgical therapy, endoscopic hemostasis for severe ulcer hemorrhage and a nonbleeding visible vessel yielded significantly better patient outcomes and was safe. This procedure may or may not yield lower direct medical costs and cost savings.