Recommendations for Screening and Monitoring the Stages of Type 1 Diabetes in the Immune Therapy Era.

Type 1 diabetes (T1D) is a complex, chronic autoimmune disease that affects over 1.6 million people in the United States. It is now understood that T1D may be undetected for many years while the disease progresses quietly without producing symptoms. T1D can be identified through diabetes-related autoantibody screening and staged accordingly, enabling healthcare providers to identify high-risk individuals in the early stages of the disease and either provide a stage-specific intervention or offer clinical trial opportunities to preserve beta cell function and anticipate the onset of clinical T1D. Evidence-based clinical practice guidelines currently do not exist for routine diabetes-related autoantibody screening of individuals at risk of developing T1D or of the general population. The purpose of this article is to help clinicians acquire an understanding of the rationale and protocols recommended for identifying patients at risk of developing T1D and monitoring such patients for autoimmune markers and progression of disease from Stage 1 to Stage 3 (clinical disease).

Type 1 diabetes (T1D) is a life-long condition where the body's immune system (which normally fights infection) mistakenly attacks cells in the pancreas that make insulin. Insulin allows one to use energy from food and controls blood sugar levels. Without early recognition and treatment, high blood sugar can cause serious symptoms and life-threatening complications, such as diabetic ketoacidosis (DKA). DKA happens when there is very low insulin, and if not spotted early, it can cause coma and death. T1D can occur at any age. The chance of getting T1D is higher if another family member has it. T1D progresses silently for months or years before symptoms appear such as increased thirst, frequent urination, and unintentional weight loss. Healthcare providers can now screen and identify people who are at early stages of T1D (without symptoms) with blood tests called autoantibodies. Early detection through screening allows people to 1) learn about the disease before symptoms start and insulin is needed, 2) potentially receive treatments that delay T1D progression, and 3) participate in research trials. By detecting T1D at early stages, people can connect with the right care team and develop the skills needed to manage later stage T1D. Early detection has been shown to prevent hospitalization and life-threatening conditions. Screening for T1D will help people maximize their opportunities to delay T1D onset while preparing for diabetes care.

Development of an evidence-based swimming representative military task to assess swimming competency in the British Army.

BACKGROUND: There is a requirement for British Army personnel to operate in/around water. Assessing role-related swimming/water competence will support personnel to conduct their job-roles safely and effectively. OBJECTIVE: To undertake a Job-Task Analysis (JTA) of British Army personnel when working in/around water and use this information to develop a Swimming Representative Military Task (RMT) to assess swimming/water competence. METHODS: Workshops, surveys, and observations were used to conduct a JTA, which identified and described job-tasks conducted by British Army personnel in/around water. Ergonomic analysis of these job-tasks identified seven water-based physical actions, which were considered fundamental for all personnel to be competent in performing. These seven actions guided design of a Swimming RMT, which was subsequently conducted twice by 103 serving personnel (89 men, 11 women) and once by 65 recruits (49 men, 16 women). RESULTS: The RMT comprised of entering the water in combat fatigues and webbing, removing webbing, swimming 50 m, and staying afloat for up to 10 minutes. During RMT trials, in trial 1, 85% of serving personnel and 74% of recruits successfully completed the RMT, which increased to 93% in serving personnel for trial 2. Across trials 1 and 2, all three timed RMT elements showed moderate-high correlational reliability (ICC range: 0.462-0.791). On average, serving personnel were quicker to complete the 50 m swim phase compared to recruits (91±24 s vs. 100±26 s; U = 2575.0, rb = -0.192, p = 0.039). CONCLUSIONS: The JTA-informed Swimming RMT provides an assessment of the minimum role-related swimming/water competence standard for British Army personnel.

Evidence of heat sensitivity in people with Parkinson's disease.

Examining how heat affects people with Parkinson's disease is essential for informing clinical decision-making, safety, well-being, and healthcare planning. While there is evidence that the neuropathology associated with Parkinson's disease affects thermoregulatory mechanisms, little attention has been given to the association of heat sensitivity to worsening symptoms and restricted daily activities in people with this progressive disease. Using a cross-sectional study design, we examined the experiences of people diagnosed with Parkinson's disease in the heat. Two-hundred and forty-seven people completed an online survey (age: 66.0 ± 9.2 years; sex: male = 102 (41.3%), female = 145 (58.7%)), of which 195 (78.9%) reported becoming more sensitive to heat with Parkinson's disease. Motor and nonmotor symptoms worsened with heat in 182 (73.7%) and 203 (82.2%) respondents, respectively. The most commonly reported symptoms to worsen included walking difficulties, balance impairment, stiffness, tremor, fatigue, sleep disturbances, excess sweating, difficulty concentrating, and light-headedness when standing. Concerningly, over half indicated an inability to work effectively in the heat, and nearly half reported that heat impacted their ability to perform household tasks and social activities. Overall, heat sensitivity was common in people with Parkinson's disease and had a significant impact on symptomology, day-to-day activities and quality of life.

Protein requirements may be lower on a training compared to rest day but are not influenced by moderate training volumes in endurance trained males.

The impact of training volume on protein requirements in endurance trained males was investigated with indicator amino acid oxidation (IAAO) methodology on a recovery day (REST) or after a 10 or 20 km run while consuming a single suboptimal protein intake (0.93 g/kg/day). Phenylalanine excretion (F13CO2; inverse proxy for whole body protein synthesis) was greatest and phenylalanine net balance was lowest on REST compared to post-exercise recovery with no difference between training volumes. Single point F13CO2 was indistinguishable from past IAAO studies using multiple protein intakes. Our results suggest that protein requirements may be greatest on recovery days but are not influenced by moderate training volumes in endurance athletes.

National Pediatrician-Scientist Collaborative Workgroup comment on new ACGME requirements' impact on pediatric physician-scientists.

BACKGROUND: The ACGME recently released its recommendation for updates to the program requirements for pediatrics. These updates proposed changes to allocation of resident clinical time and a greater emphasis on individualization. The potential impact of these changes on the training of physician-scientists is discussed. METHODS: Discussion of the proposed changes was held within the members of the National Pediatrician-Scientist Collaborative Workgroup, a group that represents scientists, trainees, program directors, chairs, and physician-scientist educators at nearly 30 residency programs from across the US with a focus on understanding and developing optimal approaches to physician-scientist training. Consideration was given to the both the personal and institutional impact of the proposal for physician-scientist development. RESULTS: Both threats and opportunities were identified. Key opportunities include the enhanced individualized training time that could be used to explore research. Threats include re-allocation of clinical training time that may strain institutions financially, expand clinical service requirements for other early career stage individuals, and alter exposure to a broad range of pediatric specialists and sub-specialists that impact career development. CONCLUSION: The NPSCW encourages consideration of the impact of changing program requirements on physician-scientist development to include ongoing discussion amongst mentors, programs, and trainees to understand and mitigate impact of new program requirements on the development of pediatrician-scientists.

Genetic complexity of diagnostically unresolved Ehlers-Danlos syndrome.

BACKGROUND: The Ehlers-Danlos syndromes (EDS) are heritable disorders of connective tissue (HDCT), reclassified in the 2017 nosology into 13 subtypes. The genetic basis for hypermobile Ehlers-Danlos syndrome (hEDS) remains unknown. METHODS: Whole exome sequencing (WES) was undertaken on 174 EDS patients recruited from a national diagnostic service for complex EDS and a specialist clinic for hEDS. Patients had already undergone expert phenotyping, laboratory investigation and gene sequencing, but were without a genetic diagnosis. Filtered WES data were reviewed for genes underlying Mendelian disorders and loci reported in EDS linkage, transcriptome and genome-wide association studies (GWAS). A genetic burden analysis (Minor Allele Frequency (MAF) <0.05) incorporating 248 Avon Longitudinal Study of Parents and Children (ALSPAC) controls sequenced as part of the UK10K study was undertaken using TASER methodology. RESULTS: Heterozygous pathogenic (P) or likely pathogenic (LP) variants were identified in known EDS and Loeys-Dietz (LDS) genes. Multiple variants of uncertain significance where segregation and functional analysis may enable reclassification were found in genes associated with EDS, LDS, heritable thoracic aortic disease (HTAD), Mendelian disorders with EDS symptomatology and syndromes with EDS-like features. Genetic burden analysis revealed a number of novel loci, although none reached the threshold for genome-wide significance. Variants with biological plausibility were found in genes and pathways not currently associated with EDS or HTAD. CONCLUSIONS: We demonstrate the clinical utility of large panel-based sequencing and WES for patients with complex EDS in distinguishing rare EDS subtypes, LDS and related syndromes. Although many of the P and LP variants reported in this cohort would be identified with current panel testing, they were not at the time of this study, highlighting the use of extended panels and WES as a clinical tool for complex EDS. Our results are consistent with the complex genetic architecture of EDS and suggest a number of novel hEDS and HTAD candidate genes and pathways.

Longitudinal Assessment of Pancreas Volume by MRI Predicts Progression to Stage 3 Type 1 Diabetes.

OBJECTIVE: This multicenter prospective cohort study compared pancreas volume as assessed by MRI, metabolic scores derived from oral glucose tolerance testing (OGTT), and a combination of pancreas volume and metabolic scores for predicting progression to stage 3 type 1 diabetes (T1D) in individuals with multiple diabetes-related autoantibodies. RESEARCH DESIGN AND METHODS: Pancreas MRI was performed in 65 multiple autoantibody-positive participants enrolled in the Type 1 Diabetes TrialNet Pathway to Prevention study. Prediction of progression to stage 3 T1D was assessed using pancreas volume index (PVI), OGTT-derived Index60 score and Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), and a combination of PVI and DPTRS. RESULTS: PVI, Index60, and DPTRS were all significantly different at study entry in 11 individuals who subsequently experienced progression to stage 3 T1D compared with 54 participants who did not experience progression (P < 0.005). PVI did not correlate with metabolic testing across individual study participants. PVI declined longitudinally in the 11 individuals diagnosed with stage 3 T1D, whereas Index60 and DPTRS increased. The area under the receiver operating characteristic curve for predicting progression to stage 3 from measurements at study entry was 0.76 for PVI, 0.79 for Index60, 0.79 for DPTRS, and 0.91 for PVI plus DPTRS. CONCLUSIONS: These findings suggest that measures of pancreas volume and metabolism reflect distinct components of risk for developing stage 3 type 1 diabetes and that a combination of these measures may provide superior prediction than either alone.

The Matthew Effect: Prevalence of Doctor and Physician Parents among Ophthalmology Applicants.

Objective This article determines the prevalence of physician parents among ophthalmology residency applications. Design Retrospective, single-center cohort study. Subjects All applicants to the University of Kentucky Ophthalmology Residency between 2018 and 2023. Methods Residency applications were reviewed, with data collection including applicant gender, self-identified Under-Represented in Medicine (URiM) status, United States Medical Licensing Examination (USMLE) Step 1 score, USMLE Step 2 score, and whether the application identified a doctor or physician as a parent. Doctor was defined as a profession requiring a doctorate degree, and similarly, physician as a profession requiring a medical degree. Results A total of 2,057 applications were reviewed, representing 54% of all match participants during the study period. Fourteen percent (296) of applications indicated a parent was a doctor and 12% (253) a parent was a physician. There were no differences between gender, URiM, USMLE Step 1, and Step 2 scores between applicants indicating a doctor or physician as a parent and those that did not ( p all > 0.4 and Cohen's d all < 0.02). Of the type of doctors, 85% (253) were physicians, 6% (17) optometrists, 6% (17) Doctors of Philosophy, 3% (8) dentists, 1% (1) pharmacist, and 1% (1) veterinarian. Eighty-six percent (217) of applications with a physician parent provided the type of physician, with ophthalmologist the most common (93, 43%). Ninety-eight percent (249) of applications with a physician parent provided the gender of the parent, with father (168, 68%) more common than mother (42, 17%) or both parents (39, 16%). Conclusion Physician parents are substantially overrepresented in ophthalmology residency applicants. This raises concerns regarding diversity and inclusion efforts for recruitment in medicine.

Transcriptomic analysis of PADI4 target genes during multi-lineage differentiation of embryonic stem cells.

During mammalian embryo development, pluripotent epiblast cells diversify into the three primary germ layers, which will later give rise to all fetal and adult tissues. These processes involve profound transcriptional and epigenetic changes that require precise coordination. Peptidylarginine deiminase IV (PADI4) is a transcriptional regulator that is strongly associated with inflammation and carcinogenesis but whose physiological roles are less well understood. We previously found that Padi4 expression is associated with pluripotency. Here, we examined the role of PADI4 in maintaining the multi-lineage differentiation potential of mouse embryonic stem (ES) cells. Using bulk and single-cell transcriptomic analyses of embryoid bodies (EBs) derived from Padi4 knock-out (Padi4-KO) mouse ES cells, we find that PADI4 loss impairs mesoderm diversification and differentiation of cardimyocytes and endothelial cells. Additionally, Padi4 deletion leads to concerted downregulation of genes associated with polarized growth, sterol metabolism and the extracellular matrix (ECM). This study indicates a requirement for Padi4 in the specification of the mesodermal lineage and reports the Padi4 associated transcriptome, providing a platform for understanding the physiological functions of Padi4 in development and homeostasis. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.

Protein Requirements Are Increased in Endurance-Trained Athletes but Similar between Females and Males during Postexercise Recovery.

PURPOSE: This study aimed to determine the daily protein requirements of female and male endurance athletes in a home-based setting using noninvasive stable isotope methodology (i.e., indicator amino acid oxidation). METHODS: Eight males (30 ± 3 yr; 78.6 ± 10.5 kg; 75.6 ± 7.5 mL·kgFFM-1·min-1; mean ± SD) and seven females (30 ± 4 yr; 57.7 ± 5.0 kg; 77.5 ± 7.1 mL·kgFFM-1·min-1) during the midluteal phase were studied. After 2 d of controlled diet (1.4 gprotein·kg-1·d-1) and training (10 and 5 km run·d-1, respectively), participants completed a 20-km run before an at-home indicator amino acid oxidation trial testing a suboptimal, a moderate, and an excess (i.e., 0.2, 1.2, and 2.0 g·kg-1·d-1, respectively) protein intake. Protein was consumed as a crystalline amino acid mixture containing [1-13C]phenylalanine to examine whole-body phenylalanine flux and phenylalanine oxidation (PheOx; the reciprocal of whole-body protein synthesis) through breath and urine sample collection. A modified biphasic linear regression determined the breakpoint in PheOx for each participant to generate an estimated average intake that would maximize whole-body protein synthesis for each sex. RESULTS: PheOx was different (P < 0.01) between all protein intakes with no effect of sex (P = 0.63). Using a modified three-point curve resulted in a breakpoint that was not different (P = 0.94) between males and females (1.60 and 1.61 g·kg-1·d-1, respectively). The recommended intake (i.e., upper 95% confidence interval) was estimated to be 1.81 and 1.89 g·kg-1·d-1 for males and females, respectively. CONCLUSIONS: Our findings indicate that endurance athletes consuming a daily protein intake toward the upper end of current consensus recommendations (~1.85 g·kg-1·d-1) will maximize whole-body protein synthesis during postexercise recovery regardless of sex.

Implementing An External Student Placement Strategy Into an Undergraduate Chiropractic Curriculum in the United Kingdom: An Education Descriptive Report.

Objective: The aim of this descriptive report is to describe the development and implementation of a placement strategy into an entry-level chiropractic course within the United Kingdom. Methods: Placements are educational experiences during which students can observe or apply theory in real practice situations. For this study, the placement strategy was developed for the chiropractic program at Teesside University through an initial working group that generated its aims, objectives, and philosophy. Evaluation surveys were completed for each module containing placement hours. The median and interquartile range (IQR) were calculated for combined responses using a Likert scale (1 = strongly agree; 5 = strongly disagree). Students were allowed to provide comments. Results: A total of 42 students participated. Placement hours were divided across all taught years (Academic Year 1: 11%; Year 2: 11%; Year 3: 26%; Year 4: 52%). Data were evaluated 2 years post-launch, with 40 students reporting to be satisfied overall with Year 1 (median 1, IQR 1-2) and Year 2 (1, IQR 1-2) placement modules. Participants perceived that placement experiences were applicable to the workplace and their future careers across modules in both Year 1 (1, IQR 1-2) and Year 2 (1, IQR 1-1.5) and that continuous feedback improved their clinical learning (Year 1 [1, IQR 1-2]; Year 2 [1, IQR 1-2]). Conclusion: This report describes the strategy and student evaluation findings over its 2-year inception, exploring the principles of interprofessional learning, reflective practice, and authentic assessment. The strategy was implemented successfully following placement acquisition and auditing processes. Student feedback reported overall satisfaction with the strategy, which was associated with graduate-ready skills.

Estimation of skeletal muscle mass in 4-year-old children using the D3-creatine dilution method.

BACKGROUND: Given limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh. METHODS: Following D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography-tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer. RESULTS: SMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: -0.031, 0.038; n = 91). CONCLUSIONS: The D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach. IMPACT: The D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Underpinning the Food Matrix Regulation of Postexercise Myofibrillar Protein Synthesis by Comparing Salmon Ingestion With the Sum of Its Isolated Nutrients in Healthy Young Adults.

BACKGROUND: Protein is most commonly consumed as whole foods as opposed to single nutrients. However, the food matrix regulation of the postprandial muscle protein synthetic response has received little attention. OBJECTIVES: The purpose of this study was to assess the effects of eating salmon (SAL) and of ingesting the same nutrients as an isolated mixture of crystalline amino acids and fish oil (ISO) on the stimulation of postexercise myofibrillar protein synthesis (MPS) and whole-body leucine oxidation rates in healthy young adults. METHODS: Ten recreationally active adults (24 ± 4 y; 5 men, 5 women) performed an acute bout of resistance exercise, followed by the ingestion of SAL or ISO in a crossover fashion. Blood, breath, and muscle biopsies were collected at rest and after exercise during primed continuous infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine. All data are presented as means ± SD and/or mean differences (95% CIs). RESULTS: Postprandial essential amino acid (EAA) concentrations peaked earlier (P = 0.024) in the ISO group than those in the SAL group. Postprandial leucine oxidation rates increased over time (P < 0.001) and peaked earlier in the ISO group (1.239 ± 0.321 nmol/kg/min; 63 ± 25 min) than those in the SAL group (1.230 ± 0.561 nmol/kg/min; 105 ± 20 min; P = 0.003). MPS rates for SAL (0.056 ± 0.022 %/h; P = 0.001) and ISO (0.046 ± 0.025 %/h; P = 0.025) were greater than the basal rates (0.020 ± 0.011 %/h) during the 0- to 5-h recovery period, with no differences between conditions (P = 0.308). CONCLUSION: We showed that the postexercise ingestion of SAL or ISO stimulate postexercise MPS rates with no differences between the conditions. Thus, our results indicate that ingesting protein from SAL as a whole-food matrix is similarly anabolic to ISO in healthy young adults. This trial was registered at www. CLINICALTRIALS: gov as NCT03870165.

Longitudinal MRI Shows Progressive Decline in Pancreas Size and Altered Pancreas Shape in Type 1 Diabetes.

CONTEXT: Individuals with type 1 diabetes (T1D) have a smaller pancreas, but longitudinal changes in pancreas size and shape are unclear. OBJECTIVE: We monitored changes in pancreas size and shape after diagnosis with T1D. DESIGN: We conducted a prospective cohort study at an academic medical center between 2014 and 2022. PATIENTS AND HEALTHY CONTROLS: Individuals with T1D (n = 91) or controls (n = 90) underwent magnetic resonance imaging (MRI) of the pancreas, including longitudinal MRI in 53 individuals with new-onset T1D. INTERVENTION: Interventions included MRI and continuous glucose monitoring (CGM). MAIN OUTCOME MEASURES: Pancreas size and shape were measured from MRI. For participants who used CGM, measures of glycemic variability were calculated. RESULTS: On longitudinal imaging, pancreas volume and pancreas volume index normalized for body weight declined during the first year after diagnosis. Pancreas volume index continued to decline through the fifth year after diagnosis. A cross-sectional study of individuals with diabetes duration up to 60 years demonstrated that pancreas size in adults negatively correlated with age and disease duration, whereas pancreas volume and pancreas volume index remained stable in controls. Pancreas volume index correlated inversely with low blood glucose index, a measure of risk for hypoglycemia. Pancreas shape was altered in individuals with T1D and further diverged from controls over the first 5 years after diagnosis. Pancreas size and shape are altered in nondiabetic individuals at genetic risk for T1D. Combined pancreas size and shape analysis better distinguished the pancreas of individuals with T1D from controls than size alone. CONCLUSIONS: Pancreas size declines most rapidly near the clinical diagnosis of T1D and continues to decline throughout adulthood. Declines in pancreas size are accompanied by changes in pancreas shape.

Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial.

OBJECTIVE: Previous studies showed that inhibiting lymphocyte costimulation reduces declining ß-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses. RESEARCH DESIGN AND METHODS: We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests. RESULTS: A total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline. CONCLUSIONS: Although abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.

Insulin Deficiency From Insulin Gene Mutation Leads to Smaller Pancreas.

OBJECTIVE: To determine the mechanism of reduced pancreas size in type 1 diabetes and the significance of islet-derived insulin in pancreatic growth. RESEARCH DESIGN AND METHODS: Using a validated and standardized MRI protocol, we measured pancreas volume and shape in a family with an autosomal-dominant insulin gene mutation that results in insulin deficiency similar in severity to that of type 1 diabetes but without autoimmunity. DNA sequencing confirmed the mutation in all four affected individuals and none of the four control family members. Insulin secretory capacity was determined by measuring postprandial urinary C-peptide. RESULTS: Family members with this form of monogenic diabetes had a markedly smaller pancreas and a severely impaired postprandial C-peptide level than family members without diabetes. CONCLUSIONS: These results suggest that severe insulin deficiency, rather than islet-directed autoimmunity, leads to reduced pancreas size in type 1 diabetes and that insulin is a major trophic factor for the exocrine pancreas.

Underestimation of Sector-Wide Methane Emissions from United States Wastewater Treatment.

An increasing percentage of US waste methane (CH4) emissions come from wastewater treatment (10% in 1990 to 14% in 2019), although there are limited measurements across the sector, leading to large uncertainties in current inventories. We conducted the largest study of CH4 emissions from US wastewater treatment, measuring 63 plants with average daily flows ranging from 4.2 × 10-4 to 8.5 m3 s-1 (<0.1 to 193 MGD), totaling 2% of the 62.5 billion gallons treated, nationally. We employed Bayesian inference to quantify facility-integrated emission rates with a mobile laboratory approach (1165 cross-plume transects). The median plant-averaged emission rate was 1.1 g CH4 s-1 (0.1-21.6 g CH4 s-1; 10th/90th percentiles; mean 7.9 g CH4 s-1), and the median emission factor was 3.4 × 10-2 g CH4 (g influent 5 day biochemical oxygen demand; BOD5)-1 [0.6-9.9 × 10-2 g CH4 (g BOD5)-1; 10th/90th percentiles; mean 5.7 × 10-2 g CH4 (g BOD5)-1]. Using a Monte Carlo-based scaling of measured emission factors, emissions from US centrally treated domestic wastewater are 1.9 (95% CI: 1.5-2.4) times greater than the current US EPA inventory (bias of 5.4 MMT CO2-eq). With increasing urbanization and centralized treatment, efforts to identify and mitigate CH4 emissions are needed.

Methane Emissions from Municipal Wastewater Collection and Treatment Systems.

Municipal wastewater collection and treatment systems are critical infrastructures, and they are also identified as major sources of anthropogenic CH4 emissions that contribute to climate change. The actual CH4 emissions at the plant- or regional level vary greatly due to site-specific conditions as well as high seasonal and diurnal variations. Here, we conducted the first quantitative analysis of CH4 emissions from different types of sewers and water resource recovery facilities (WRRFs). We examined variations in CH4 emissions associated with methods applied in different monitoring campaigns, and identified main CH4 sources and sinks to facilitate carbon emission reduction efforts in the wastewater sector. We found plant-wide CH4 emissions vary by orders of magnitude, from 0.01 to 110 g CH4/m3 with high emissions associated with plants equipped with anaerobic digestion or stabilization ponds. Rising mains show higher dissolved CH4 concentrations than gravity sewers when transporting similar raw sewage under similar environmental conditions, but the latter dominates most collection systems around the world. Using the updated data sets, we estimated annual CH4 emission from the U.S. centralized, municipal wastewater treatment to be approximately 10.9 ± 7.0 MMT CO2-eq/year, which is about twice as the IPCC (2019) Tier 2 estimates (4.3-6.1 MMT CO2-eq/year). Given CH4 emission control will play a crucial role in achieving net zero carbon goals by the midcentury, more studies are needed to profile and mitigate CH4 emissions from the wastewater sector.