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B-cell VH region repertoire sequencing of eight anatomical sites in six human donors reveals distinct networks of clone distribution. B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks—one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B-cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

Early life differentiation and regulatory function of human T cells is confined to particular anatomical sites. It is unclear how the immune response in early life becomes appropriately stimulated to provide protection while also avoiding excessive activation as a result of diverse new antigens. T cells are integral to adaptive immunity; mouse studies indicate that tissue localization of T cell subsets is important for both protective immunity 1 , 2 , 3 , 4 and immunoregulation 5 , 6 . In humans, however, the early development and function of T cells in tissues remain unexplored. We present here an analysis of lymphoid and mucosal tissue T cells derived from pediatric organ donors in the first two years of life, as compared to adult organ donors, revealing early compartmentalization of T cell differentiation and regulation. Whereas adult tissues contain a predominance of memory T cells 7 , 8 , in pediatric blood and tissues the main subset consists of naive recent thymic emigrants, with effector memory T cells (T EM ) found only in the lungs and small intestine. Additionally, regulatory T (T reg ) cells comprise a high proportion (30–40%) of CD4 + T cells in pediatric tissues but are present at much lower frequencies (1–10%) in adult tissues. Pediatric tissue T reg cells suppress endogenous T cell activation, and early T cell functionality is confined to the mucosal sites that have the lowest T reg :T EM cell ratios, which suggests control in situ of immune responses in early life.

B cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B cell clones are distributed in the body, we sequenced 933,427 B cell clonal lineages and mapped them to 8 different anatomic compartments in 6 human organ donors. We show that large B cell clones partition into two broad networks—one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

Aging, higher prevalence of diabetes, worsening obesity, and hyperglycemia among potential donors increase the likelihood that pancreata will be declined by transplant centers. Hemoglobin A1c testing, also known as glycated hemoglobin testing, identifies a donor's average blood glucose concentration for the preceding 2 to 3 months and is the standard test for identifying prolonged periods of hyperglycemia. To compare pancreas utilization rates before and after implementation of hemoglobin A1c testing. A retrospective study of data from the New York Organ Donor Network was conducted. Potential donors were defined as standard criteria donors who had no history of diabetes and were not seropositive for hepatitis B or C. Criteria for \"ideal\" potential pancreas donors were based on age, body mass index, lipase level, and terminal creatinine level. Potential donors who did not meet the criteria for ideal donors were considered \"expanded\" potential pancreas donors. Pancreas utilization rate was defined as the number of pancreata transplanted divided by the number of potential pancreas donors. Of 779 standard criteria donors, 691 (89%) were potential pancreas donors: 251 ideal (36%) and 440 expanded (64%) donors. In 2005 and 2006, before hemoglobin A1c testing, pancreas utilization rates were 21% and 18%, respectively. In 2008, 2009, and 2010, after hemoglobin A1c testing was incorporated, utilization rates were 27%, 28%, and 32%, respectively. Utilization of ideal donors increased from 33% to 51% (P= .003), and utilization of expanded donors increased from 11% to 17% (P= .05). Pancreas utilization increased 51.0%, and pancreas discards decreased 50.8% with the implementation of hemoglobin A1c testing. Hemoglobin A1c testing may increase utilization of ideal and expanded criteria pancreata.

Context Aging, higher prevalence of diabetes, worsening obesity, and hyperglycemia among potential donors increase the likelihood that pancreata will be declined by transplant centers. Hemoglobin Alc testing, also known as glycated hemoglobin testing, identifies a donor's average blood glucose concentration for the preceding 2 to 3 months and is the standard test for identifying prolonged periods of hyperglycemia. Objective To compare pancreas utilization rates before and after implementation of hemoglobin Alc testing. Design A retrospective study of data from the New York Organ Donor Network was conducted. Potential donors were defined as standard criteria donors who had no history of diabetes and were not seropositive for hepatitis B or C. Criteria for “ideal” potential pancreas donors were based on age, body mass index, lipase level, and terminal creatinine level. Potential donors who did not meet the criteria for ideal donors were considered “expanded” potential pancreas donors. Pancreas utilization rate was defined as the number of pancreata transplanted divided by the number of potential pancreas donors. Results Of 779 standard criteria donors, 691 (89%) were potential pancreas donors: 251 ideal (36%) and 440 expanded (64%) donors. In 2005 and 2006, before hemoglobin Alc testing, pancreas utilization rates were 21% and 18%, respectively. In 2008, 2009, and 2010, after hemoglobin Alc testing was incorporated, utilization rates were 27%, 28%, and 32%, respectively. Utilization of ideal donors increased from 33% to 51% (P = .003), and utilization of expanded donors increased from 11% to 17% (P = .05). Pancreas utilization increased 51.0%, and pancreas discards decreased 50.8% with the implementation of hemoglobin Alc testing. Conclusion Hemoglobin Alc testing may increase utilization of ideal and expanded criteria pancreata.

Aging, higher prevalence of diabetes, worsening obesity, and hyperglycemia among potential donors increase the likelihood that pancreata will be declined by transplant centers. Hemoglobin A1c testing, also known as glycated hemoglobin testing, identifies a donor's average blood glucose concentration for the preceding 2 to 3 months and is the standard test for identifying prolonged periods of hyperglycemia. To compare pancreas utilization rates before and after implementation of hemoglobin A1c testing. A retrospective study of data from the New York Organ Donor Network was conducted. Potential donors were defined as standard criteria donors who had no history of diabetes and were not seropositive for hepatitis B or C. Criteria for \"ideal\" potential pancreas donors were based on age, body mass index, lipase level, and terminal creatinine level. Potential donors who did not meet the criteria for ideal donors were considered \"expanded\" potential pancreas donors. Pancreas utilization rate was defined as the number of pancreata transplanted divided by the number of potential pancreas donors. Of 779 standard criteria donors, 691 (89%) were potential pancreas donors: 251 ideal (36%) and 440 expanded (64%) donors. In 2005 and 2006, before hemoglobin A1c testing, pancreas utilization rates were 21% and 18%, respectively. In 2008, 2009, and 2010, after hemoglobin A1c testing was incorporated, utilization rates were 27%, 28%, and 32%, respectively. Utilization of ideal donors increased from 33% to 51% (P= .003), and utilization of expanded donors increased from 11% to 17% (P= .05). Pancreas utilization increased 51.0%, and pancreas discards decreased 50.8% with the implementation of hemoglobin A1c testing. Hemoglobin A1c testing may increase utilization of ideal and expanded criteria pancreata.

In 1985 we presented results of a randomized trial involving 1843 women followed for five years that indicated that segmental breast resection (lumpectomy) followed by breast irradiation is appropriate therapy for patients with Stage I or II breast cancer (tumor size, ≤4 cm), provided that the margins of the resected specimens are free of tumor. Women with positive axillary nodes received adjuvant chemotherapy. Lumpectomy followed by irradiation resulted in a five-year survival rate of 85 percent, as compared with 76 percent for total mastectomy, a rate of survival free of distant disease of 76 percent, as compared with 72 percent, and a disease-free survival rate of 72 percent, as compared with 66 percent. In the current study, we have extended our observations through eight years of follow-up. Ninety percent of the women treated with breast irradiation after lumpectomy remained free of ipsilateral breast tumor, as compared with 61 percent of those not treated with irradiation after lumpectomy (P<0.001). Among patients with positive axillary nodes, only 6 percent of those treated with radiation and adjuvant chemotherapy had a recurrence of tumor in the ipsilateral breast. Lumpectomy with or without irradiation of the breast resulted in rates of disease-free survival (58±2.6 percent), distant-disease-free survival (65±2.6 percent), and overall survival (71 ±2.6 percent) that were not significantly different from those observed after total mastectomy (54±2.4 percent, 62±2.3 percent, and 71 ±2.4 percent, respectively). There was no significant difference in the rates of distant-disease–free survival (P = 0.2) or survival (P = 0.3) among the women who underwent lumpectomy (with or without irradiation), despite the greater incidence of recurrence of tumor in the ipsilateral breast in those who received no radiation. We conclude that our observations through eight years are consistent with the findings at five years and that these new findings continue to support the use of lumpectomy in patients with Stage I or II breast cancer. We also conclude that irradiation reduces the probability of local recurrence of tumor in patients treated with lumpectomy. (N Engl J Med 1989;320:822–8.) RESULTS of a clinical trial (Protocol B-06) conducted by the National Surgical Adjuvant Breast and Bowel Project to evaluate segmental mastectomy (lumpectomy) in the treatment of Stages I and II breast cancers ≤4 cm in size were published in 1985. 1 Life-table estimates through five years after surgery indicated that more than 90 percent of the women who underwent segmental mastectomy with axillary-node dissection and breast irradiation remained free of cancer in the ipsilateral breast and that the rates of disease-free survival, survival free of disease at distant sites (distant-disease–free survival), and overall survival were not significantly different from those among . . .

In 1976 we began a randomized trial to evaluate breast conservation by a segmental mastectomy in the treatment of Stage I and II breast tumors ≤4 cm in size. The operation removes only sufficient tissue to ensure that margins of resected specimens are free of tumor. Women were randomly assigned to total mastectomy, segmental mastectomy alone, or segmental mastectomy followed by breast irradiation. All patients had axillary dissections, and patients with positive nodes received chemotherapy. Life-table estimates based on data from 1843 women indicated that treatment by segmental mastectomy, with or without breast irradiation, resulted in disease-free, distant-disease–free, and overall survival at five years that was no worse than that after total breast removal. In fact, disease-free survival after segmental mastectomy plus radiation was better than disease-free survival after total mastectomy (P = 0.04), and overall survival after segmental mastectomy, with or without radiation, was better than overall survival after total mastectomy (P = 0.07, and 0.06, respectively). A total of 92.3 per cent of women treated with radiation remained free of breast tumor at five years, as compared with 72.1 per cent of those receiving no radiation (P<0.001). Among patients with positive nodes 97.9 per cent of women treated with radiation and 63.8 per cent of those receiving no radiation remained tumor-free (P<0.001), although both groups received chemotherapy. We conclude that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors ≤4 cm, provided that margins of resected specimens are free of tumor. (N Engl J Med 1985; 312:665–73.) Anecdotal information has been presented by the pioneers 1 2 3 4 5 6 and more recent proponents 7 8 9 10 11 of breast preservation for the management of primary breast cancer. Although they have not clearly determined the relative merits of such a therapeutic approach by comparing it directly with more conventional methods of management, those observers have demonstrated that patients could survive free of disease after limited surgery and radiation therapy. The rationale that was employed to justify the use of the regimen is obscure. There was no biologic principle that directed the endeavor. In many instances the procedure was performed because patients refused a recommended radical . . .

The bishop writes that the North Shore takeover would erode the patient base for St. John's Episcopal in Smithtown and that this would close that hospital. That closing, he then tells us, would force the \"loss\" of a hospital in Far Rockaway and three nursing homes, as well as the collapse of a $2.5-million annual commitment to Interfaith Hospital in Brooklyn and $10 million worth of free care to Interfaith's surrounding community. In addition, plans would die for 240 nursing-home beds in Bedford-Stuyvesant and a hospice in Brooklyn. St. John's and the University Hospital at Stony Brook, which also opposes the North Shore proposal, have worried in print about losing patients or losing referrals. But Community Hospital is too small to accommodate all of St. John's patients. [Bishop Orris G. Walker Jr.] seems to assume that competition is bad. Actually, there isn't enough in health care. Both Stony Brook and St. John's can only become more community-minded, better and stronger to meet the challenge of a reinvigorated North Shore-Community Hospital.