Gender and Autism Program: A novel clinical service model for gender-diverse/transgender autistic youth and young adults.

Objective: Situated in Children's National Hospital (CNH)'s Neuropsychology Division, the Gender and Autism Program (GAP) is the first clinical service dedicated to the needs of autistic gender-diverse/transgender youth. This study describes GAP clinical assessment profiles and presents a multi-perspective programmatic review of GAP evaluation services. Method: Seventy-five consecutive gender- and neuropsychologically-informed GAP evaluations were analyzed, including demographics, gender and autism characterization, and primary domains evaluated. Three program-based Delphi studies were conducted and identify: clinician priorities and challenges in providing care, program administrator lessons learned and ongoing barriers, and considerations adapting this model for a rural academic medical center. Results: Nearly two-thirds of referrals were transfeminine. Most youth had existing autism diagnoses; of those undiagnosed, three-quarters were found to be autistic. Five goals of evaluations were identified: Mental health was always assessed, and most evaluations also assessed gender-related needs in the context of autism neurodiversity. Neuropsychological characterization of strengths and challenges informed personalized accommodations to support youth gender-related self-advocacy. Clinicians emphasized frequent youth safety concerns. Administrators emphasized the need for specialized training for working with families. Components for adaptation of the GAP in a rural academic medical center were identified. Conclusions: Since its founding, the GAP has proven a sustainable neuropsychology-based service with consistent referral flow and insurance authorizations. Capturing staff perspectives through rigorous Delphi methods, and addressing the GAP's feasibility and replicability, this study provides a road map for replicating this service. We also highlight GAP training of specialist clinicians, fundamental to addressing the desperate shortage of providers in this field.

A Clinical Program for Transgender and Gender-Diverse Neurodiverse/Autistic Adolescents Developed through Community-Based Participatory Design.

Objective: A series of studies report elevated rates of autism and autistic characteristics among gender-diverse youth seeking gender services. Although youth with the co-occurrence present with complex care needs, existing studies have focused on co-occurrence rates. Further, clinical commentaries have emphasized provider-centered interpretations of clinical needs rather than key stakeholder-driven clinical approaches. This study aimed to employ community-based participatory research methodologies to develop a key stakeholder-driven clinical group program.Method: Autistic/neurodiverse gender-diverse (A/ND-GD) youth (N = 31), parents of A/ND-GD youth (N = 46), A/ND-GD self-advocates (N = 10), and expert clinical providers (N = 10) participated in a multi-stage community-based participatory procedure. Needs assessment data were collected repeatedly over time from A/ND-GD youth and their parents as the youth interacted with one another through ongoing clinical groups, the curriculum of which was developed progressively through the iterative needs assessments.Results: Separate adolescent and parent needs assessments revealed key priorities for youth (e.g., the importance of connecting with other A/ND-GD youth and the benefit of experiencing a range of gender-diverse role models to make gender exploration and/or gender affirmation more concrete) and parents (e.g., the need for A/ND-related supports for their children as well as provision of an A/ND-friendly environment that fosters exploration of a range of gender expressions/options). Integration and translation of youth and parent priorities resulted in 11 novel clinical techniques for this population.Conclusions: With generally high acceptability ratings for each component of the group program, this study presents a community-driven clinical model to support broad care needs and preferences of A/ND-GD adolescents.

Genomic signals of migration and continuity in Britain before the Anglo-Saxons.

The purported migrations that have formed the peoples of Britain have been the focus of generations of scholarly controversy. However, this has not benefited from direct analyses of ancient genomes. Here we report nine ancient genomes (∼ 1 ×) of individuals from northern Britain: seven from a Roman era York cemetery, bookended by earlier Iron-Age and later Anglo-Saxon burials. Six of the Roman genomes show affinity with modern British Celtic populations, particularly Welsh, but significantly diverge from populations from Yorkshire and other eastern English samples. They also show similarity with the earlier Iron-Age genome, suggesting population continuity, but differ from the later Anglo-Saxon genome. This pattern concords with profound impact of migrations in the Anglo-Saxon period. Strikingly, one Roman skeleton shows a clear signal of exogenous origin, with affinities pointing towards the Middle East, confirming the cosmopolitan character of the Empire, even at its northernmost fringes.

Efficacy, safety and tolerability of atorvastatin in dyslipidemic subjects with advanced (non-nephrotic) and endstage chronic renal failure.

BACKGROUND: Patients with dyslipidemia and advanced renal failure are at markedly increased risk of cardiovascular morbidity and mortality. We evaluated the efficacy, safety, and tolerability of atorvastatin in non-nephrotic, dyslipidemic patients with chronic renal failure (CRF) or endstage renal failure (ESRF) receiving dialysis. METHODS: Following a 6-week baseline period, adult patients meeting Australian Heart Foundation treatment guidelines received atorvastatin for 16 weeks: 19 with CRF (predialysis), 17 on hemodialysis (HD), and 13 on continuous ambulatory peritoneal dialysis (CAPD). Dose (10-40 mg daily) was titrated to achieve lipid-lowering targets. Efficacy was determined by monitoring lipids (principally triglycerides and low-density lipoprotein [LDL] cholesterol); safety and tolerance by monitoring clinical and laboratory parameters. RESULTS: Atorvastatin was effective in reducing LDL cholesterol from baseline at each of weeks 4, 8, 12, and 16 in all study groups, with reductions of more than 40% at week 16. Sixty-two percent of PD, 73% of HD, and 100% of CRF patients were at or below target (<2.6 mmol/l) for LDL cholesterol at week 16. Significant reductions in triglycerides (approximately 27%) were seen in the CRF and combined HD/CAPD groups at all time points. Depending on the group, 65%-83% of patients were at or below target (<2.0 mmol/l) for triglycerides at week 16. The majority of patients received the 10-mg dose. Atorvastatin also reduced total cholesterol and apolipoprotein B levels in all groups and very-low-density lipoprotein (VLDL) cholesterol in the CRF group. Significant increases in LDL particle size were found in the HD and combined HD/CAPD groups. Minor, particularly gastrointestinal, symptoms were common. Three patients reported musculoskeletal symptoms, but creatine kinase was raised in only one. CONCLUSION: Atorvastatin is an effective lipid-lowering agent for dyslipidemic subjects with advanced and endstage renal failure, and was reasonably well tolerated.

Safety and efficacy of simvastatin in hypercholesterolemic patients undergoing chronic renal dialysis.

Dyslipidemia is universal but hypercholesterolemia per se is present in around 50% of dialysis patients. Although dietary therapy is of benefit in some, the majority require drug therapy. We compared the efficacy and safety of simvastatin plus an optimized lipid-lowering dialysis diet with placebo plus diet in a randomized, double-blind trial stratified for dialysis modality. Patients treated with hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) for at least 9 months and with serum non-high-density lipoprotein (HDL) cholesterol greater than 135 mg/dL, low-density lipoprotein (LDL) greater than 116 mg/dL, and triglyceride less than 600 mg/dL after a 6-week dietary treatment phase and an 8-week diet plus placebo run-in phase, were enrolled in the 24-week double-blind treatment phase. Fifty-seven patients (16 men, 41 women, median age 63 years, range 22-75 yr) were randomized 2:1 to diet plus 5 mg/day simvastatin (n = 38: 22 HD, 16 CAPD) or diet plus placebo (n = 19: 12 HD, 7 CAPD) for 24 weeks. Dose was doubled bimonthly (maximum 20 mg/day) if non-HDL cholesterol was greater than 135 mg/dL. Forty-two patients (73.7%) completed the trial. Comparing baseline and 24 weeks, simvastatin (median 10 mg/day) was significantly more effective than placebo in reducing serum non-HDL cholesterol concentrations. For HD, the median percentage changes for total cholesterol (TC) (simvastatin versus placebo) were -21.4% and -12.1% (P = 0.011), respectively; for LDL cholesterol, -33.0% and -8.8% (P = 0.023); for non-HDL cholesterol, -25.2% and -14.0% (P = 0.008); and for TC:HDL, -17.65% and -1.67% (P = 0.008). For CAPD, changes for TC were -22.1% and -1.5% (P = 0.003), respectively; for LDL, -36.4% and 0.0% (P = 0.001); for non-HDL cholesterol, -24.9% and -3.6% (P = 0.002); and for TC:HDL ratio, -21.49% and +9.74% (P = 0.045). Changes with CAPD in apolipoprotein (Apo) A1 were -4.7% and +4.0% (P = 0.031); and for ApoB, -19.9% and +2.6%, respectively (P = 0.031). There were no significant changes in ApoA1 or ApoB with HD. Compared with placebo, triglyceride levels fell 10.2% with HD and 6.2% with CAPD. HDL cholesterol was unchanged with HD but rose 8.5% with CAPD. These trends, however, did not reach statistical significance (P > 0.05). There was no effect on Lp (a). The incidence of clinical and laboratory adverse experiences were not increased in the simvastatin-treated patients compared with placebo. Simvastatin appears to be a safe and effective treatment for the reduction of serum non-HDL cholesterol levels in both HD and, particularly, CAPD patients.