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In 2021, the Adolescents 360 (A360) project pursued a human-centered design (HCD) process to layer complementary economic empowerment components on top of its existing sexual and reproductive health (SRH) interventions targeting adolescent girls aged 15 to 19. Given the volume of evidence informing successful approaches for improving economic and empowerment outcomes for adolescents, we pursued an intentionally evidence-informed and gender-intentional design process, while trying to also respond directly to user insights. In this open letter, we share how we utilized and validated the evidence-base while applying the core tenets of HCD (empathy and user insights) to design holistic, layered programming for girls. We describe three overarching categories which depict how we used the existing evidence and new user insights to strengthen our design process. Often the evidence base allowed us to expedite finding a solution that worked for our users. However, at times there was a disconnect between what we knew worked in the evidence base and what our users said they wanted. New insights also allowed us to build a greater understanding of our users’ lived experiences where there were existing evidence gaps. We were aided by the engagement of a technical partner, BRAC, who synthesized evidence for our design teams and functioned as an ‘on demand’ support mechanism as questions and challenges arose. Yet, the volume of information to absorb almost guaranteed that we would miss out on the opportunity to apply certain evidence-based practices. We encourage researchers to consider how to make evidence more easily digestible to practitioners and for the whole community of practice to work together to identify what questions need to be asked to effectively operationalize evidence in a local context.

Abstract Objective Accumulation of misfolded superoxide dismutase‐1 (SOD1) is a pathological hallmark of SOD1‐related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts. Methods We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured. Results In participants with heterozygous SOD1A5V mutations, known to cause rapidly progressive ALS, mutant SOD1 protein exhibited ~twofold faster turnover and ~ 16‐fold lower concentration compared to wild‐type SOD1 protein. SDGPVKV levels were increased in SOD1A5V carriers relative to controls. Thus, SOD1 mutations impact protein kinetics and stability. We applied this approach to sporadic ALS participants and found that SOD1 turnover, concentration, and SDGPVKV levels are not significantly different compared to controls. Interpretation These results highlight the ability of stable isotope labeling approaches and peptide deamidation to discern the influence of disease mutations on protein kinetics and stability and support implementation of this method to optimize clinical trial design of gene and molecular therapies for neurological disorders. Trial Registration Clinicaltrials.gov: NCT03449212.

Abstract Background Early in the pandemic, inadequate SARS-CoV-2 testing limited understanding of transmission. Chief among barriers to large-scale testing was unknown feasibility, particularly in non-urban areas. Our objective was to report methods of high-volume, comprehensive SARS-CoV-2 testing, offering one model to augment disease surveillance in a rural community. Methods A community-university partnership created an operational site used to test most residents of Bolinas, California regardless of symptoms in 4 days (April 20th – April 23rd, 2020). Prior to testing, key preparatory elements included community mobilization, pre-registration, volunteer recruitment, and data management. On day of testing, participants were directed to a testing lane after site entry. An administrator viewed the lane-specific queue and pre-prepared test kits, linked to participants’ records. Medical personnel performed sample collection, which included finger prick with blood collection to run laboratory-based antibody testing and respiratory specimen collection for polymerase chain reaction (PCR). Results Using this 4-lane model, 1,840 participants were tested in 4 days. A median of 57 participants (IQR 47–67) were tested hourly. The fewest participants were tested on day 1 (n = 338 participants), an intentionally lower volume day, increasing to n = 571 participants on day 4. The number of testing teams was also increased to two per lane to allow simultaneous testing of multiple participants on days 2–4. Consistent staffing on all days helped optimize proficiency, and strong community partnership was essential from planning through execution. Conclusions High-volume ascertainment of SARS-CoV-2 prevalence by PCR and antibody testing was feasible when conducted in a community-led, drive-through model in a non-urban area.

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.