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A series of recent studies in humans and the NOD mouse model have highlighted the central role that autoimmunity directed against insulin, in particular the insulin B chain 9-23 peptide, may play in the pathogenesis of type 1 diabetes. Both pathogenic and protective T-cell clones recognizing the B:9-23 peptide have been produced. This report describes the successful creation of BDC12-4.1 T-cell receptor (TCR) transgenic mice with spontaneous insulitis in F1 mice (FVB x NOD) and spontaneous diabetes in NOD.RAG(-/-) (backcross 1 generation). Disease progression is heterogeneous and is modified by a series of genetic factors including heterozygosity (H-2(g7)/H-2(q)) versus homozygosity for H-2(g7), the presence of additional T-/B-cell receptor-rearranged genes (RAG(+) versus RAG(-/-)), and the insulin 2 gene knockout (the insulin gene expressed in the NOD thymus). Despite lymphopenia, 40% of H-2(g7/g7) BDC12-4.1 TCR(+) RAG(-/-) Ins2(-/-) mice are diabetic by 10 weeks of age. As few as 13,500 transgenic T-cells from a diabetic TCR(+) RAG(-/-) mouse can transfer diabetes to an NOD.scid mouse. The current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes at NOD backcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis. [ABSTRACT FROM AUTHOR]

The Voyager 2 flyby of Uranus in 1986 revealed an unusually oblique and off-centred magnetic field. This single in situ measurement has been the basis of our interpretation of Uranus's magnetosphere as the canonical extreme magnetosphere of the solar system; with inexplicably intense electron radiation belts and a severely plasma-depleted magnetosphere. However, the role of external forcing by the solar wind has rarely been considered in explaining these observations. Here we revisit the Voyager 2 dataset to show that Voyager 2 observed Uranus's magnetosphere in an anomalous, compressed state that we estimate to be present less than 5% of the time. If the spacecraft had arrived only a few days earlier, the upstream solar wind dynamic pressure would have been ~20 times lower, resulting in a dramatically different magnetospheric configuration. We postulate that such a compression of the magnetosphere could increase energetic electron fluxes within the radiation belts and empty the magnetosphere of its plasma temporarily. Therefore, the interpretation of Uranus's magnetosphere as being extreme may simply be a product of a flyby that occurred under extreme upstream solar wind conditions., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Study Design: Longitudinal cohort study., Purpose: To determine the effect of change in interspace height on fusion and postoperative neck pain., Overview of Literature: The optimal height of a cervical interbody device (cage) in anterior cervical discectomy and fusion (ACDF) is not well defined. In addition, the effect of interspace distraction on fusion and postoperative neck pain remains unclear., Methods: We retrospectively reviewed the charts of consecutive patients who underwent one- or two-level ACDF using polyetheretherketone cages by multiple surgeons from January 2015 to June 2016. We excluded patients younger than 18 years old, patients who had prior surgery at the same level (s), those with two-stage procedures, and those with less than 3 months of followup. Fusion was determined using the "Song" criteria. Ordinal regression was used to determine predictors of fusion. Patient-reported outcomes (PRO) were analyzed., Results: We identified 323 consecutive patients. Twenty-two patients met the exclusion criteria. A total of 435 operative levels were included in the 301 remaining patients. Interspace fusion did not significantly vary by increasing interspace height with fusion rates between 76.2% and 82.8% at a mean follow-up of 17.9±12.6 months. The effect of an increase in interspace height and neck pain PRO was available for 163 patients who underwent one-level ACDF at a mean follow-up period of 16.2±13.1 months. We found no significant difference in fusion rate or neck pain score with increasing interspace height from 1 to 8 mm. Ordinal regression demonstrated no significant predictors of fusion., Conclusions: Interspace distraction from 1 to 8 mm did not result in significantly different pseudarthrosis rates or postoperative neck pain.

At Mercury, several processes can release ions and neutrals out of the planet's surface. Here we present enhancements of planetary ions (Na + -group ions) in Mercury's northern magnetospheric cusp during flux transfer event (FTE) "showers." FTE showers are intervals of intense dayside magnetopause reconnection, during which FTEs are observed in quick succession, that is, only separated by a few seconds. This study identifies 1953 FTE shower intervals and 1795 Non-FTE shower intervals. During the shower intervals, this study shows that the FTEs form a solar wind entry layer equatorward of the northern magnetospheric cusp. In this entry layer, solar wind ions are accelerated and move downward (i.e., planetward) toward the cusp, which sputter upward-moving planetary ions with a particle flux of 1 × 10 11  m -2  s -1 within 1 min. The precipitation rate is estimated to increase by an order of magnitude during FTE showers, to 2 × 10 25  s -1 , and the neutral density of the exosphere could vary by >10% in response to this FTE-driven sputtering. Such rapid large-scale variations driven by dayside reconnection may explain the minute-to-minute changes in Mercury's exosphere, especially on the high latitudes, observed by ground-based telescopes on Earth. Our MESSENGER in situ observation of enhanced planetary ions in the entry layer likely corresponds to an escape channel for Mercury's planetary ions. Comprehensive, future multipoint measurements made by BepiColombo will greatly enhance our understanding of the processes contributing to Mercury's dynamic exosphere and magnetosphere., (©2022. The Authors.)

Chronic encapsulated intracerebral hematoma is a rare pathology which may present after spontaneous intracerebral hemorrhage (ICH) or radiosurgery for arteriovenous malformations. A 66-year-old male presented with recent diagnosis of cerebrovascular accident (CVA) status post-treatment with tissue plasminogen activator and mechanical thrombectomy. His recent diagnoses included infective endocarditis, septic bacteremia, meningitis, and aspiration pneumonia. One month following his CVA, the patient presented with delayed altered mental status. In the setting of increasing lethargy, computed tomography and magnetic resonance imaging of the brain were performed, which suggested a brain abscess, septic emboli, and ventriculitis. The patient was taken to surgery emergently. Intraoperatively, the patient was found to have an encapsulated mass of liquid consistency. Tissue pathology demonstrated ischemic cortical tissue and hemorrhage. Multiple cultures were negative for growth. The patient was ultimately determined to have an encapsulated intracerebral hematoma. Encapsulated intracerebral hematoma should be a part of the differential diagnosis when presented with a brain abscess in the setting of a patient who is at risk of ICH., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Yoon et al.)

We present the first investigation and quantification of the photoionization loss process to Mercury's sodium exosphere from spacecraft and ground-based observations. We analyze plasma and neutral sodium measurements from NASA's MESSENGER spacecraft and the THEMIS telescope. We find that the sodium ion (Na + ) content and therefore the significance of photoionization varies with Mercury's orbit around the Sun (i.e., true anomaly angle: TAA). Na + production is affected by the neutral sodium solar-radiation acceleration loss process. More Na + was measured on the inbound leg of Mercury's orbit at 180°-360° TAA because less neutral sodium is lost downtail from radiation acceleration. Calculations using results from observations show that the photoionization loss process removes ∼10 24 atoms/s from the sodium exosphere (maxima of 4 × 10 24 atoms/s), showing that modeling efforts underestimate this loss process. This is an important result as it shows that photoionization is a significant loss process and larger than loss from radiation acceleration., (© 2021. Jet Propulsion Laboratory. California Institute of Technology. Government sponsorship acknowledged.)

Background: Telemedicine refers to various modalities for remote care, including telephone calls, imaging review, and real-time video teleconferencing visits. Although it has not been widely used in outpatient neurosurgery settings, the COVID-19 (coronavirus disease 2019) pandemic has necessitated a broader adoption. Our goal is to show the level of patient satisfaction with their telemedicine care., Methods: We prospectively studied consecutive telemedicine patients who scheduled outpatient neurosurgery visits from May 15 to June 8, 2020. Patients were seen by the surgeon via real-time video conferencing using Google Meet, and then completed a telemedicine satisfaction survey. Our primary outcome was telemedicine satisfaction scores. We compared satisfaction scores between new and established patients and between patients within and outside of a 15-mile radius of the nearest clinic location. Sensitivity analyses were performed to account for the nonrespondents. Descriptive and univariate analyses were performed. A P value of <0.05 was considered significant., Results: Five-hundred and ninety patients completed a telemedicine visit during the study period. One patient from out of state was excluded. Three-hundred and ten patients (52.6%) responded. The average age was 60.9 ± 13.60 years; 59% were female, 20.6% were new patients; the average distance to the clinic was 28.03 ± 36.09 km (17.42 ± 22.43 miles). The mean overall satisfaction score was 6.32 ± 1.27. Subgroup analyses by new/established patient status and distance from their home to the clinic showed no significant difference in mean satisfaction scores between groups., Conclusions: Telemedicine provided a viable and satisfactory option for neurosurgical patients in the outpatient setting during the COVID-19 pandemic., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Mercury has a global dayside exosphere, with measured densities of 10 -2  cm -3 at ~1500 km. Here we report on the inferred enhancement of neutral densities (<10 2  cm -3 ) at high altitudes (~5300 km) by the MESSENGER spacecraft. Such high-altitude densities cannot be accounted for by the typical exosphere. This event was observed by the Fast-Imaging Plasma Spectrometer (FIPS), which detected heavy ions of planetary origin that were recently ionized, and "picked up" by the solar wind. We estimate that the neutral density required to produce the observed pickup ion fluxes is similar to typical exospheric densities found at ~700 km altitudes. We suggest that this event was most likely caused by a meteroid impact. Understanding meteoroid impacts is critical to understanding the source processes of the exosphere at Mercury, and the use of plasma spectrometers will be crucial for future observations with the Bepi-Colombo mission.

We report the first Jupiter X-ray observations planned to coincide with an interplanetary coronal mass ejection (ICME). At the predicted ICME arrival time, we observed a factor of ∼8 enhancement in Jupiter's X-ray aurora. Within 1.5 h of this enhancement, intense bursts of non-Io decametric radio emission occurred. Spatial, spectral, and temporal characteristics also varied between ICME arrival and another X-ray observation two days later. Gladstone et al. (2002) discovered the polar X-ray hot spot and found it pulsed with 45 min quasiperiodicity. During the ICME arrival, the hot spot expanded and exhibited two periods: 26 min periodicity from sulfur ions and 12 min periodicity from a mixture of carbon/sulfur and oxygen ions. After the ICME, the dominant period became 42 min. By comparing Vogt et al. (2011) Jovian mapping models with spectral analysis, we found that during ICME arrival at least two distinct ion populations, from Jupiter's dayside, produced the X-ray aurora. Auroras mapping to magnetospheric field lines between 50 and 70  R J were dominated by emission from precipitating sulfur ions (S 7+,…,14+ ). Emissions mapping to closed field lines between 70 and 120  R J and to open field lines were generated by a mixture of precipitating oxygen (O 7+,8+ ) and sulfur/carbon ions, possibly implying some solar wind precipitation. We suggest that the best explanation for the X-ray hot spot is pulsed dayside reconnection perturbing magnetospheric downward currents, as proposed by Bunce et al. (2004). The auroral enhancement has different spectral, spatial, and temporal characteristics to the hot spot. By analyzing these characteristics and coincident radio emissions, we propose that the enhancement is driven directly by the ICME through Jovian magnetosphere compression and/or a large-scale dayside reconnection event.

We report on the first analysis of magnetospheric cusp observations at Saturn by multiple in situ instruments onboard the Cassini spacecraft. Using this we infer the process of reconnection was occurring at Saturn's magnetopause. This agrees with remote observations that showed the associated auroral signatures of reconnection. Cassini crossed the northern cusp around noon local time along a poleward trajectory. The spacecraft observed ion energy-latitude dispersions-a characteristic signature of the terrestrial cusp. This ion dispersion is "stepped," which shows that the reconnection is pulsed. The ion energy-pitch angle dispersions suggest that the field-aligned distance from the cusp to the reconnection site varies between ∼27 and 51 R S . An intensification of lower frequencies of the Saturn kilometric radiation emissions suggests the prior arrival of a solar wind shock front, compressing the magnetosphere and providing more favorable conditions for magnetopause reconnection., Key Points: We observe evidence for reconnection in the cusp plasma at SaturnWe present evidence that the reconnection process can be pulsed at SaturnSaturn's cusp shows similar characteristics to the terrestrial cusp.

Background: Historically, extended haplotypes have been defined using only a few data points, such as alleles for several HLA genes in the MHC. High-density SNP data, and the increasing affordability of whole genome SNP typing, creates the opportunity to define higher resolution extended haplotypes. This drives the need for new tools that support quantification and visualization of extended haplotypes as defined by as many as 2000 SNPs. Confronted with high-density SNP data across the major histocompatibility complex (MHC) for 2,300 complete families, compiled by the Type 1 Diabetes Genetics Consortium (T1DGC), we developed software for studying extended haplotypes., Methods: The software, called ExHap (Extended Haplotype), uses a similarity measurement we term congruence to identify and quantify long-range allele identity. Using ExHap, we analyzed congruence in both the T1DGC data and family-phased data from the International HapMap Project., Results: Congruent chromosomes from the T1DGC data have between 96.5% and 99.9% allele identity over 1,818 SNPs spanning 2.64 megabases of the MHC (HLA-DRB1 to HLA-A). Thirty-three of 132 DQ-DR-B-A defined haplotype groups have > 50% congruent chromosomes in this region. For example, 92% of chromosomes within the DR3-B8-A1 haplotype are congruent from HLA-DRB1 to HLA-A (99.8% allele identity). We also applied ExHap to all 22 autosomes for both CEU and YRI cohorts from the International HapMap Project, identifying multiple candidate extended haplotypes., Conclusions: Long-range congruence is not unique to the MHC region. Patterns of allele identity on phased chromosomes provide a simple, straightforward approach to visually and quantitatively inspect complex long-range structural patterns in the genome. Such patterns aid the biologist in appreciating genetic similarities and differences across cohorts, and can lead to hypothesis generation for subsequent studies.

Background: We recently reported an association between Type 1 diabetes and the telomeric major histocompatibility complex (MHC) single nucleotide polymorphism (SNP) rs1233478. As further families have been analyzed in the Type 1 Diabetes Genetics Consortium (T1DGC), we tested replication of the association and, with more data, analyzed haplotypic associations., Methods: An additional 2717 case and 1315 control chromosomes have been analyzed from the T1DGC, with human leukocyte antigen (HLA) typing and data for 2837 SNPs across the MHC region., Results: We confirmed the association of rs1233478 (new data only: P=2.2E-5, OR=1.4). We also found two additional SNPs nearby that were significantly associated with Type 1 diabetes (new data only rs3131020: P=8.3E-9, OR=0.65; rs1592410: P=2.2E-8, OR=1.5). For studies of Type 1 diabetes in the MHC region, it is critical to account for linkage disequilibrium with the HLA genes. Logistic regression analysis of these new data indicated that the effects of rs3131020 and rs1592410 on Type 1 diabetes risk are independent of HLA alleles (rs3131020: P=2.3E-3, OR=0.73; rs1592410: P=2.1E-3, OR=1.4). Haplotypes of 12 SNPs (including the three highly significant SNPs) stratify diabetes risk (high risk, protective, and neutral), with high-risk haplotypes limited to approximately 20,000 bp in length. The 20,000-bp region is telomeric of the UBD gene and contains LOC729653, a hypothetical gene., Conclusions: We believe that polymorphisms of the telomeric MHC locus LOC729653 may confer risk for Type 1 diabetes., (© 2011 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.)

Aims/hypothesis: We investigated the risk associated with HLA-B*39 alleles in the context of specific HLA-DR/DQ haplotypes., Methods: We studied a readily available dataset from the Type 1 Diabetes Genetics Consortium that consists of 2,300 affected sibling pair families genotyped for both HLA alleles and 2,837 single nucleotide polymorphisms across the major histocompatibility complex region., Results: The B*3906 allele significantly enhanced the risk of type 1 diabetes when present on specific HLA-DR/DQ haplotypes (DRB1 0801-DQB1 0402: p = 1.6 × 10(-6), OR 25.4; DRB1 0101-DQB1 0501: p = 4.9 × 10(-5), OR 10.3) but did not enhance the risk of DRB1 0401-DQB1 0302 haplotypes. In addition, the B 3901 allele enhanced risk on the DRB1 1601-DQB1 0502 haplotype (p = 3.7 × 10(-3), OR 7.2)., Conclusions/interpretation: These associations indicate that the B 39 alleles significantly increase risk when present on specific HLA-DR/DQ haplotypes, and HLA-B typing in concert with specific HLA-DR/DQ genotypes should facilitate genetic prediction of type 1 diabetes, particularly in a research setting.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is the third major locus affecting risk of type I diabetes (T1D), after HLA-DR/DQ and INS. The most associated single-nucleotide polymorphism (SNP), rs2476601, has a C->T variant and results in an arginine (R) to tryptophan (W) amino acid change at position 620. To assess whether this, or other specific variants, are responsible for T1D risk, the Type I Diabetes Genetics Consortium analyzed 28 PTPN22 SNPs in 2295 affected sib-pair (ASP) families. Transmission Disequilibrium Test analyses of haplotypes revealed that all three haplotypes with a T allele at rs2476601 were overtransmitted to affected children, and two of these three haplotypes showed statistically significant overtransmission (P=0.003 to P=5.9E-12). Another haplotype had decreased transmission to affected children (P=3.5E-05). All haplotypes containing the rs2476601 T allele were identical for all SNPs across PTPN22 and only varied at centromeric SNPs. When considering rs2476601 'C' founder chromosomes, a second haplotype (AGGGGC) centromeric of PTPN22 in the C1orf178 region was associated with protection from T1D (odds ratio=0.81, P=0.0005). This novel finding requires replication in independent populations. We conclude the major association of PTPN22 with T1D is likely due to the recognized non-synonymous SNP rs2476601 (R620W).

Objective: The objective of this study was to define the spectrum of TCR beta chains permissive for T cells with alpha chains containing the conserved TRAV5D-4*04 sequence to target the insulin B:9-23 peptide, a major epitope for initiation of diabetes in the NOD mouse., Materials and Methods: We produced T cell hybridomas from mice with single T cell receptors (BDC12-4.1 TCR alpha(+)beta(+) double transgenic mice and BDC12-4.4 TCR alpha(+)beta(+) double retrogenic mice) or from mice with only the corresponding alpha chains transgene or retrogene and multiple endogenous TCR beta chains., Results: Hybridomas with the complete BDC12-4.1 and BDC12-4.4 T cell receptors, despite having markedly different TCR beta chains, responded to similar B:9-23 peptides. Approximately 1% of the hybridomas from mice with the fixed TRAV5D-4*04 alpha chains and multiple endogenous beta chains responded to B:9-23 peptides while the majority of hybridomas with different beta chains did not respond. There was no apparent conservation of TCR beta chain sequences in the responding hybridomas., Conclusions: Approximately 1% of hybridomas utilizing different TCR beta chains paired with the conserved TRAV5D-4*04 containing alpha chains respond to insulin peptide B:9-23. Therefore, TCR beta chain sequences make an important contribution to insulin B:9-23 peptide recognition but multiple beta chain sequences are permissive for recognition.

The availability of both HLA data and genotypes for thousands of SNPs across the major histocompatibility complex (MHC) in 1240 complete families of the Type 1 Diabetes Genetics Consortium allowed us to analyze the occurrence and extent of megabase contiguous identity for founder chromosomes from unrelated individuals. We identified 82 HLA-defined haplotype groups, and within these groups, megabase regions of SNP identity were readily apparent. The conserved chromosomes within the 82 haplotype groups comprise approximately one third of the founder chromosomes. It is currently unknown whether such frequent conservation for groups of unrelated individuals is specific to the MHC, or if initial binning by highly polymorphic HLA alleles facilitated detection of a more general phenomenon within the MHC. Such common identity, specifically across the MHC, impacts type 1 diabetes susceptibility and may impact transplantation between unrelated individuals.

Aim: The goal of this study was to develop and implement methodology that would aid in the analysis of extended high-density single nucleotide polymorphism (SNP) major histocompatibility complex (MHC) haplotypes combined with human leucocyte antigen (HLA) alleles in relation to type 1 diabetes risk., Methods: High-density SNP genotype data (2918 SNPs) across the MHC from the Type 1 Diabetes Genetics Consortium (1240 families), in addition to HLA data, were processed into haplotypes using PedCheck and Merlin, and extended DR3 haplotypes were analysed., Results: With this large dense set of SNPs, the conservation of DR3-B8-A1 (8.1) haplotypes spanned the MHC (>/=99% SNP identity). Forty-seven individuals homozygous for the 8.1 haplotype also shared the same homozygous genotype at four 'sentinel' SNPs (rs2157678 'T', rs3130380 'A', rs3094628 'C' and rs3130352 'T'). Conservation extended from HLA-DQB1 to the telomeric end of the SNP panels (3.4 Mb total). In addition, we found that the 8.1 haplotype is associated with lower risk than other DR3 haplotypes by both haplotypic and genotypic analyses [haplotype: p = 0.009, odds ratio (OR) = 0.65; genotype: p = 6.3 x 10(-5), OR = 0.27]. The 8.1 haplotype (from genotypic analyses) is associated with lower risk than the high-risk DR3-B18-A30 haplotype (p = 0.01, OR = 0.23), but the DR3-B18-A30 haplotype did not differ from other non-8.1 DR3 haplotypes relative to diabetes association., Conclusion: The 8.1 haplotype demonstrates extreme conservation (>3.4 Mb) and is associated with significantly lower risk for type 1 diabetes than other DR3 haplotypes.

NOD mice with knockout of both native insulin genes and a mutated proinsulin transgene, alanine at position B16 in preproinsulin (B16:A-dKO mice), do not develop diabetes. Transplantation of NOD islets, but not bone marrow, expressing native insulin sequences (tyrosine at position B16) into B16:A-dKO mice rapidly restored development of insulin autoantibodies (IAAs) and insulitis, despite the recipients' pancreatic islets lacking native insulin sequences. Splenocytes from B16:A-dKO mice that received native insulin-positive islets induced diabetes when transferred into wild-type NOD/SCID or B16:A-dKO NOD/SCID mice. Splenocytes from mice immunized with native insulin B chain amino acids 9-23 (insulin B:9-23) peptide in CFA induced rapid diabetes upon transfer only in recipients expressing the native insulin B:9-23 sequence in their pancreata. Additionally, CD4(+) T cells from B16:A-dKO mice immunized with native insulin B:9-23 peptide promoted IAAs in NOD/SCID mice. These results indicate that the provision of native insulin B:9-23 sequences is sufficient to prime anti-insulin autoimmunity and that subsequent transfer of diabetes following peptide immunization requires native insulin B:9-23 expression in islets. Our findings demonstrate dependence on B16 alanine versus tyrosine of insulin B:9-23 for both the initial priming and the effector phase of NOD anti-islet autoimmunity.

Type 1A diabetes mellitus is caused by specific and progressive autoimmune destruction of the beta cells in the islets of Langerhans whereas the other cell types in the islet (alpha, delta, and PP) are spared. The autoantigens of Type 1A diabetes may be divided into subgroups based on their tissue distributions: Beta-cell-specific antigens like insulin, insulin derivatives, and IGRP (Islet-specific Glucose-6-phosphatase catalytic subunit Related Peptide); neurendocrine antigens such as carboxypeptidase H, insulinoma-associated antigen (IA-2), glutamic acid decarboxylase (GAD65), and carboxypeptidase E; and those expressed ubiquitously like heat shock protein 60 (a putative autoantigen for type 1 diabetes). This review will focus specifically on insulin as a primary autoantigen, an essential target for disease, in type 1A diabetes mellitus. In particular, immunization with insulin peptide B:9-23 can be used to induce insulin autoantibodies and diabetes in animal models or used to prevent diabetes. Genetic manipulation of the insulin 1 and 2 genes reciprocally alters development of diabetes in the NOD mouse, and insulin gene polymorphisms are important determinants of childhood diabetes. We are pursuing the hypothesis that insulin is a primary autoantigen for type 1 diabetes, and thus the pathogenesis of the disease relates to specific recognition of one or more peptides.

Type 1A (immune-mediated) diabetes results from T-cell-mediated specific destruction of the islet beta cells that produce insulin (1). One can divide the development of diabetes into a series of overlapping stages beginning with genetic susceptibility and ending with complete beta cell destruction (2). The dominant genetic susceptibility locus is the major histocompatibility complex (MHC), also called the human leukocyte antigen (HLA) region in humans, and in particular, immune response genes DR and DQ (3). Additionally, the existence of a series of rare but informative "single-gene" disorders associated with autoimmune diabetes indicates that a number of different immunologic lesions can lead to autoimmune diabetes. The most common forms of type 1A diabetes are polygenic (multifactorial) disorders with unidentified environmental factors contributing to the disease. Given current information, it is now possible to predict the development of type 1A diabetes (4, 5), and major efforts are under way to create preventive therapies., (Copyright 2005 Prous Science. All rights reserved.)