Transgender Population Size in the United States: a Meta-Regression of Population-Based Probability Samples.

BackgroundTransgender individuals have a gender identity that differs from the sex they were assigned at birth. The population size of transgender individuals in the United States is not well-known, in part because official records, including the US Census, do not include data on gender identity. Population surveys today more often collect transgender-inclusive gender-identity data, and secular trends in culture and the media have created a somewhat more favorable environment for transgender people.ObjectivesTo estimate the current population size of transgender individuals in the United States and evaluate any trend over time.Search methodsIn June and July 2016, we searched PubMed, Cumulative Index to Nursing and Allied Health Literature, and Web of Science for national surveys, as well as "gray" literature, through an Internet search. We limited the search to 2006 through 2016.Selection criteriaWe selected population-based surveys that used probability sampling and included self-reported transgender-identity data.Data collection and analysisWe used random-effects meta-analysis to pool eligible surveys and used meta-regression to address our hypothesis that the transgender population size estimate would increase over time. We used subsample and leave-one-out analysis to assess for bias.Main resultsOur meta-regression model, based on 12 surveys covering 2007 to 2015, explained 62.5% of model heterogeneity, with a significant effect for each unit increase in survey year (F = 17.122; df = 1,10; b = 0.026%; P = .002). Extrapolating these results to 2016 suggested a current US population size of 390 adults per 100 000, or almost 1 million adults nationally. This estimate may be more indicative for younger adults, who represented more than 50% of the respondents in our analysis.Authors' conclusionsFuture national surveys are likely to observe higher numbers of transgender people. The large variety in questions used to ask about transgender identity may account for residual heterogeneity in our models. Public health implications. Under- or nonrepresentation of transgender individuals in population surveys is a barrier to understanding social determinants and health disparities faced by this population. We recommend using standardized questions to identify respondents with transgender and nonbinary gender identities, which will allow a more accurate population size estimate

CD28− and CD28lowCD8+ Regulatory T Cells: Of Mice and Men

Since the rebirth of regulatory (formerly known as suppressor) T cells in the early 1990s, research in the field of immune-regulation by various T cell populations has quickly gained momentum. While T cells expressing the transcription factor Foxp3 are currently in the spotlight, several other T cell populations endowed with potent immunomodulatory capacities have been identified in both the CD8(+) and CD4(+) compartment. The fundamental difference between CD4(+) and CD8(+) T cells in terms of antigen recognition suggests non-redundant, and perhaps complementary, functions of regulatory CD4(+) and CD8(+) T cells in immunoregulation. This emphasizes the importance and necessity of continuous research on both subpopulations of regulatory T cells (Tregs) so as to decipher their complex physiological relevance and possible synergy. Two distinct CD8-expressing Treg populations can be distinguished based on expression of the co-stimulatory receptor CD28. Here, we review the literature on these (at least in part) thymus-derived CD28(low) and peripherally induced CD28(−)CD8(+) Tregs

Hysteresis and bi-stability by an interplay of calcium oscillations and action potential firing

Many cell types exhibit oscillatory activity, such as repetitive action potential firing due to the Hodgkin-Huxley dynamics of ion channels in the cell membrane or reveal intracellular inositol triphosphate (IP$_3$) mediated calcium oscillations (CaOs) by calcium-induced calcium release channels (IP$_3$-receptor) in the membrane of the endoplasmic reticulum (ER). The dynamics of the excitable membrane and that of the IP$_3$-mediated CaOs have been the subject of many studies. However, the interaction between the excitable cell membrane and IP$_3$-mediated CaOs, which are coupled by cytosolic calcium which affects the dynamics of both, has not been studied. This study for the first time applied stability analysis to investigate the dynamic behavior of a model, which includes both an excitable membrane and an intracellular IP$_3$-mediated calcium oscillator. Taking the IP$_3$ concentration as a control parameter, the model exhibits a novel rich spectrum of stable and unstable states with hysteresis. The four stable states of the model correspond in detail to previously reported growth-state dependent states of the membrane potential of normal rat kidney fibroblasts in cell culture. The hysteresis is most pronounced for experimentally observed parameter values of the model, suggesting a functional importance of hysteresis. This study shows that the four growth-dependent cell states may not reflect the behavior of cells that have differentiated into different cell types with different properties, but simply reflect four different states of a single cell type, that is characterized by a single model.Comment: 29 pages, 6 figure

Surgical treatment of secondary glaucoma in non-infectious pediatric uveitis

Secondary glaucoma in pediatric non-infectious uveitis is a very complex andstill potentially blinding disease. Blindness can be prevented in most cases with adequate controle of intraocular pressure (IOP), often requiring a surgical intervention. Known options for a surgical intervention include angle surgery (trabeculodialysis, goniotomy, or trabeculotomy), fistulizing procedures (trabeculectomy), glaucomadrainage implant (GDI; Molteno GDI, Ahmed GDI, or Baerveldt GDI), or cyclophotocoagulation. In our review, all interventions are able to reduce IOP to an acceptable level, with cyclophotocoagulation having the shortest effect. In addition, the complication rate varies widely per intervention. We performed two studies to investigate the differences between interventions, focusing on the complication/re-intervention rate per intervention and thereby the impact of the overall treatment pathway, in order to identify an effective treatment pathway for these children with the least impact on the quality of life. We retrospectively compared the outcomes of a trabeculectomy and a GDI procedure, and observed that GDIs had higher success rates, with a lower number of re-interventions. In addition, we retrospectively analyzing the outcomes of a goniotomy procedure in the current century, in which uveitis can be optimally controlled in most cases, thanks to the introduction of anti-TNF-alpha (a type of ‘biological’ (disease-modifying antirheumatic drug)). This study indicates that a goniotomy procedure is safe and straightforward, effective over a 5-year follow-up period, with an 86% success rate (which is superior compared to the other interventions), and might be considered as the best surgical options in these children

Hematopoietic Chimerism and Transplantation Tolerance: A Role for Regulatory T Cells

The immunosuppressive regimens currently used in transplantation to prevent allograft destruction by the host’s immune system have deleterious side effects and fail to control chronic rejection processes. Induction of donor-specific non-responsiveness (i.e., immunological tolerance) to transplants would solve these problems and would substantially ameliorate patients’ quality of life. It has been proposed that bone marrow or hematopoietic stem-cell transplantation, and resulting (mixed) hematopoietic chimerism, lead to immunological tolerance to organs of the same donor. However, a careful analysis of the literature, performed here, clearly establishes that whereas hematopoietic chimerism substantially prolongs allograft survival, it does not systematically prevent chronic rejection. Moreover, the cytotoxic conditioning regimens used to achieve long-term persistence of chimerism are associated with severe side effects that appear incompatible with a routine use in the clinic. Several laboratories recently embarked on different studies to develop alternative strategies to overcome these issues. We discuss here recent advances obtained by combining regulatory T cell infusion with bone-marrow transplantation. In experimental settings, this attractive approach allows development of genuine immunological tolerance to donor tissues using clinically relevant conditioning regimens

Goniotomy for Non-Infectious Uveitic Glaucoma in Children

Secondary glaucoma is still a blinding complication in childhood uveitis, for which most commonly used surgical interventions (trabeculectomy or glaucoma drainage implant) involve multiple re-interventions and/or complications postoperatively. The goniotomy procedure has never been investigated in the current era, in which patients with pediatric uveitis receive biologics as immunosuppressive therapy for a prolonged period, with potential implications for the outcome. The purpose of the study is to evaluate the efficacy and safety of a goniotomy procedure in pediatric non-infectious uveitis in a retrospective, multicenter case series. The primary outcomes were the postoperative intraocular pressure (IOP), number of IOP-lowering medications, and success rate. Postoperative success was defined as 6 ≤ IOP ≤ 21 mmHg, without major complications or re-interventions. Fifteen eyes of ten children were included. Median age of the included patients at goniotomy was 7 years; median follow-up was 59 months. Median (interquartile range) IOP before surgery was 30 (26–34) mmHg with 4 (3–4) IOP-lowering medications. At 1, 2, and 5 years after goniotomy, median IOP was 15, 14, and 15 mmHg with 2 (0–2), 1 (0–2), and 0 (0–2) medications, respectively (p &lt; 0.001 postoperatively versus preoperatively for all timepoints). Success rate was 100%, 93%, and 80% after 1, 2, and 5 years, respectively. There were no significant changes in visual acuity and uveitis activity or its treatment, and there were no major complications. Our results show that the goniotomy is an effective and safe surgery for children with uveitic glaucoma.</p

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis

Purpose: To identify factors associated with glaucoma surgery in pediatric uveitis. Methods: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. Results: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP &gt; 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. Conclusion: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.</p

Factors Associated With Glaucoma Surgery in Pediatric Non-Infectious Uveitis

Purpose: To identify factors associated with glaucoma surgery in pediatric uveitis. Methods: Patients diagnosed with uveitis before their 18th birthday and with an observation period of at least one year were included in a retrospective case-control study. Results: A total of 185 patients were included, 84 of whom had undergone glaucoma surgery. Juvenile idiopathic arthritis (JIA)-related uveitis was associated with undergoing glaucoma surgery (p = .002). In the JIA-subgroup, the presence of anterior segment complications (OR 3.1 (95% CI 1.0 to 9.6); P = .045) and an IOP &gt; 21 mmHg during the first uveitis remission (OR 4.5 (95% CI 1.3 to 15.2); P = .015) were associated with an increased risk of glaucoma surgery. Sixty-eight percent of the cases needed glaucoma surgery within one year after they started IOP-lowering triple therapy. Conclusion: The risk profile for undergoing glaucoma surgery as outlined in this study is a valuable help to recognize and treat secondary glaucoma in a timely manner.</p