T lymphocytes and B lymphocytes integrate activating signals to control the size of their proliferative response. Here we report that such control was achieved by timed changes in the production rate of cell-cycle-regulating proto-oncoprotein Myc, with division cessation occurring when Myc levels fell below a critical threshold. The changing pattern of the level of Myc was not affected by cell division, which identified the regulating mechanism as a cell-intrinsic, heritable temporal controller. Overexpression of Myc in stimulated T cells and B cells did not sustain cell proliferation indefinitely, as a separate 'time-to-die' mechanism, also heritable, was programmed after lymphocyte activation and led to eventual cell loss. Together the two competing cell-intrinsic timed fates created the canonical T cell and B cell immune-response pattern of rapid growth followed by loss of most cells. Furthermore, small changes in these timed processes by regulatory signals, or by oncogenic transformation, acted in synergy to greatly enhance cell numbers over time.

BackgroundPredominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy.ObjectivesTo characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia.MethodsWe identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features.Results179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16–87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort.ConclusionOur data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.

Obesity is a major public health concern around the world, including Asia. Bariatric surgery has grown in popularity to combat this rising trend. An e-mail questionnaire survey was sent to all the representative Asia-Pacific Metabolic and Bariatric Surgery Society (APMBSS) members of 12 leading Asian countries to provide bariatric surgery data for the last 5 years (2005-2009). The data provided by representative members were discussed at the 6th International APMBSS Congress held at Singapore between 21st and 23rd October 2010. Eleven nations except China responded. Between 2005 and 2009, a total of 6,598 bariatric procedures were performed on 2,445 men and 4,153 women with a mean age of 35.5 years (range, 18-69years) and mean BMI of 44.27 kg/m(2) (range, 31.4-73 kg/m(2)) by 155 practicing surgeons. Almost all of the operations were performed laparoscopically (99.8%). For combined years 2005-2009, the four most commonly performed procedures were laparoscopic adjustable gastric banding (LAGB, 35.9%), laparoscopic standard Roux-en-Y gastric bypass (LRYGB, 24.3%), laparoscopic sleeve gastrectomy (LSG, 19.5%), and laparoscopic mini gastric bypass (15.4%). Comparing the 5-year trend from 2004 to 2009, the absolute numbers of bariatric surgery procedures in Asia increased from 381 to 2,091, an increase of 5.5 times. LSG increased from 1% to 24.8% and LRYGB from 12% to 27.7%, a relative increase of 24.8 and 2.3 times, whereas LAGB and mini gastric bypass decreased from 44.6% to 35.6% and 41.7% to 6.7%, respectively. The absolute growth rate of bariatric surgery in Asia over the last 5 years was 449%.