Endocrine treatment of gender-dysphoric/gender-incongruent persons : an Endocrine Society clinical practice guideline

Objective: To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009. Participants: The participants include an Endocrine Societyappointed task force of nine experts, a methodologist, and a medical writer. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus Process: Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. Conclusion: Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the persons genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the persons affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment

Reconsidering the Barefoot Doctor Programme

This paper examines the widely acclaimed Barefoot Doctor campaign in China. The Barefoot Doctor Campaign has come to symbolize the success of Chinese health care to the extent that it has become a model for WHO public health strategy. Yet little has been done to understand how or whether it worked on the ground and what difficulties and contradictions emerged in its implementation. Using previously unexplored party archives as well as newly collected oral interviews, this paper moves away from a narrow focus on party politics and policy formulation by examining the reality of health care at the local level and the challenges faced by local authorities and individuals as the campaigns evolved

Lithium in the aragonite skeletons of massive Porites corals: A new tool to reconstruct tropical sea surface temperatures

Previous studies have demonstrated the potential for the Li content of coral aragonite to record information about environmental conditions, but no detailed study of tropical corals exists. Here we present the Li and Mg to Ca ratios at a bimonthly to monthly resolution over 25 years in two modern Porites corals, the genus most often used for paleoclimate reconstructions in the tropical Indo-Pacific. A strong relationship exists between coral Li/Ca and locally measured SST, indicating that coral Li/Ca can be used to reconstruct tropical SST variations. However, Li/Ca ratios of the skeleton deposited during 1979-1980 do not track local SST well and are anomalously high in places. The Mg/Ca ratios of this interval are also anomalously high, and we suggest Li/Ca can be used to reconstruct tropical SST only when Mg/Ca data are used to carefully screen for relatively rare biological effects. Mg/Li or Li/Mg ratios provide little advantage over Li/Ca ratios, except that the slope of the Li/Mg temperature relationship is more similar between the two corals. The Mg/Li temperature relationship for the coral that experienced a large temperature range is similar to that found for cold water corals and aragonitic benthic foraminifera in previous studies. The comparison with data from other biogenic aragonites suggests the relationship between Li/Mg and water temperature can be described by a single exponential relationship. Despite this hint at an overarching control, it is clear that biological processes strongly influence coral Li/Ca, and more calibration work is required before widely applying the prox

Evaluating the Mental Models Approach to Developing a Risk Communication: A Scoping Review of the Evidence

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordRisk communication is fundamental in ensuring people are equipped with the knowledge needed to navigate varied risks. One generally well-regarded framework for the development of such communications is the mental models approach to risk communication (MMARC). Developed during the 1990s, the MMARC has been applied to a range of health, technological, and environmental risks. However, as yet, we know of no attempt to collate and review articles that evaluated communications developed using the MMARC. This article took a first step at addressing this gap by conducting a scoping review that aimed to begin to explore the fidelity with which the approach has been applied, explore whether there appeared to be sufficient studies to warrant a future systematic review, and identify future research questions. Although the initial search found over 100 articles explicitly applying the MMARC, only 12 of these developed a risk-related communication that was tested against a control (and thus included in the current review). All studies reported a positive effect of the MMARC versus control communication for at least some of the outcome measures (knowledge being the most prevalent). However, there was wide variation between studies including type of control, outcomes assessed, and only five studies reported adopting a randomized design. The review highlights both the need for greater fidelity in the way future studies operationalize the MMARC approach, and suggests that a full-scale systematic review of the MMARC literature appears justified, especially given the possibility of a large gray literature in this area.This was part of a PhD project funded by the European Social Fund Convergence Programme for Cornwall and the Isles of Scilly. The European Centre for Environment and Human Health (part of the University of Exeter Medical School) is part financed by the European Regional Development Fund Programme 2007 to 2013 and European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs.To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria.This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment