Infant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with anxiety-relevant genetic variation.

An anxious or inhibited temperament (IT) early in life is a major risk factor for the later development of stress-related psychopathology. Starting in infancy, nonhuman primates, like humans, begin to reveal their temperament when exposed to novel situations. Here, in Study 1 we demonstrate this infant IT predicts adult behavior. Specifically, in over 600 monkeys, we found that individuals scored as inhibited during infancy were more likely to refuse treats offered by potentially-threatening human experimenters as adults. In Study 2, using a sample of over 4000 monkeys from a large multi-generational family pedigree, we demonstrate that infant IT is partially heritable. The data revealed infant IT to reflect a co-inherited substrate that manifests across multiple latent variables. Finally, in Study 3 we performed whole-genome sequencing in 106 monkeys to identify IT-associated single-nucleotide variations (SNVs). Results demonstrated a genome-wide significant SNV near CTNNA2, suggesting a molecular target worthy of additional investigation. Moreover, we observed lower p values in genes implicated in human association studies of neuroticism and depression. Together, these data demonstrate the utility of our model of infant inhibited temperament in the rhesus monkey to facilitate discovery of genes that are relevant to the long-term inherited risk to develop anxiety and depressive disorders.

Clinical presentation, treatment, and genetic and histopathological analysis of juvenile cataracts and secondary glaucoma in a rhesus macaque (Macaca mulatta).

This report describes the clinical and histological findings, genetic study, and treatment in a 1.3-year-old rhesus macaque with bilateral cataracts and unilateral secondary glaucoma. Intravitreal injection of gentamicin decreased the intraocular pressure from 56 to <2 mm Hg. A putative genetic cause of the cataracts was not identified.

Magee Equations™ and response to neoadjuvant chemotherapy in ER+/HER2-negative breast cancer: a multi-institutional study.

Magee Equations™ (ME) are multivariable models that can estimate oncotype DX® recurrence score. One of the equations, Magee Equation 3 (ME3) which utilizes only semi-quantitative receptor results has been shown to provide chemopredictive value in the neoadjuvant setting in a single institutional study. This multi-institutional study (seven institutions contributed cases) was undertaken to examine the validity of ME3 in predicting response to neoadjuvant chemotherapy in estrogen receptor positive, HER2-negative breast cancers. Stage IV cases were excluded. The primary endpoint was the pathologic complete response (pCR) rate in different categories of ME3 scores calculated based on receptor results in the pre-therapy core biopsy. A total of 166 cases met the inclusion criteria. The patient age ranged from 24 to 83 years (median 53 years). The average pre-therapy tumor size was 3.9 cm, and axillary lymph nodes were confirmed positive by pre-therapy core biopsy in 85 of 166 cases (51%). The pCR rate according to ME3 scores was 0% (0 of 64) in ME3 < 18, 0% (0 of 46) in ME3 18-25, 14% (3 of 21) in ME3 > 25 to <31, and 40% (14 of 35) in ME3 score 31 or higher (p value: <0.0001). There were no distant recurrences and no deaths in the 17 patients with pCR. In the remaining 149 cases with residual disease, ME3 score of >25 was significantly associated with shorter distant recurrence-free survival and showed a trend for shorter breast cancer-specific survival. The results of this multi-institutional study are similar to previously published data from a single institution (PMID: 28548119) and confirm the chemo-predictive value of ME3 in the neoadjuvant setting. In addition, ME3 may provide prognostic information in patients with residual disease which should be further evaluated.

Generalized basaloid follicular hamartoma syndrome: a case report and review of the literature.

Basaloid follicular hamartoma (BFH) is a rare, generally benign lesion of importance because of its clinical and histopathological similarity to infundibulocystic basal cell carcinoma. Autosomal dominant generalized BFH syndrome is 1 of the 5 clinical forms of BFH that has been described in the literature. We report a case of BFH syndrome in a 47-year-old Hispanic female who presented with an increasing number of small 1- to 2-mm tan to brown smooth facial papules, few palmar pits, and cobblestoning of the tongue. Her mother had similar lesions on her face. A biopsy of one of the patient's facial lesions confirmed the diagnosis of BFH. Of note, this patient later presented with rapid growth of one of her facial lesions, and a subsequent biopsy confirmed the development of a basal cell carcinoma arising within one of her BFH lesions. Although BFH is classically stable for years and does not require immediate surgical removal, our case highlights the importance of continual monitoring of these patients, given the potential for malignant transformation of these lesions.

Observed Thermal Impacts of Wind Farms Over Northern Illinois.

This paper assesses impacts of three wind farms in northern Illinois using land surface temperature (LST) data from the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments onboard the Terra and Aqua satellites for the period 2003-2013. Changes in LST between two periods (before and after construction of the wind turbines) and between wind farm pixels and nearby non-wind-farm pixels are quantified. An areal mean increase in LST by 0.18-0.39 °C is observed at nighttime over the wind farms, with the geographic distribution of this warming effect generally spatially coupled with the layout of the wind turbines (referred to as the spatial coupling), while there is no apparent impact on daytime LST. The nighttime LST warming effect varies with seasons, with the strongest warming in winter months of December-February, and the tightest spatial coupling in summer months of June-August. Analysis of seasonal variations in wind speed and direction from weather balloon sounding data and Automated Surface Observing System hourly observations from nearby stations suggest stronger winds correspond to seasons with greater warming and larger downwind impacts. The early morning soundings in Illinois are representative of the nighttime boundary layer and exhibit strong temperature inversions across all seasons. The strong and relatively shallow inversion in summer leaves warm air readily available to be mixed down and spatially well coupled with the turbine. Although the warming effect is strongest in winter, the spatial coupling is more erratic and spread out than in summer. These results suggest that the observed warming signal at nighttime is likely due to the net downward transport of heat from warmer air aloft to the surface, caused by the turbulent mixing in the wakes of the spinning turbine rotor blades.

TRASER: acute phase vascular and follicular changes.

BACKGROUND AND OBJECTIVES: A TRASER (Total Reflection Amplification of Spontaneous Emission of Radiation) is a novel device that utilizes the energy from a flashlamp to induce the spontaneous emission of photons from a fluorescent medium. This study was designed to observe clinical and histological changes of skin treated with two different fluorescent media selected for their peak emissions tuned for vascular and hair follicle targets. STUDY DESIGN/MATERIALS AND METHODS: A purpuric clinical response for the vascular target was assessed with a TRASER using the fluorescent medium Pyrromethene 556 producing a narrow spectrum peaking at 544 nm. Using a 12 mm spot and pulse duration of 1 ms, treatment pulses with fluences of 6.0-9.5 J/cm2 were given along the forearm of subject with photo type II skin. Follicular structures were targeted with the dye cell switched to Sulforhodamine 640 Chloride, producing a narrow peak at 654 nm. Using a 12 mm spot, single 20 ms pulses with fluencies from 14.0 to 20.0 J/cm2 were delivered with 5 °C contact cooling to the shaved chest of a subject with photo type II skin with brown hair. Clinical observations were photographed and assessed by two physicians. A 4 mm punch skin biopsy was taken at approximately 60 and 30 minutes respectively for both the vascular and hair regions. The paraffin embedded H&E stained vertical sections were analyzed by a dermatopathologist. RESULTS: A characteristic threshold purpuric response was noted at 7.2 J/cm2 . The histological changes consistently showed intravascular thrombosis of the small sub-dermal plexus of capillaries down to larger vessels approaching the subcutaneous fat. There were no extravasated red blood cells. Clinical hair follicle target changes of perifollicular edema and transient erythema, similar to those described with standard hair removal lasers, were noted. Histologically these were shown to be limited to the target structures. CONCLUSION: This is the first demonstration of clinical and histological acute phase changes associated with use of a TRASER with wavelengths optimized for vascular and follicular targets. The findings of this observational study support the notion that the TRASER can be used as an effective vascular and hair removal device.

ICU outcomes following a Central Line Associated Blood Stream Infections (CLABSI) reduction quality improvement project.

BACKGROUND: Central Line Associated Blood Stream Infections (CLABSI) are significant complications for hospitalized patients. Several different approaches have been used to reduce CLABSI. OBJECTIVE: This study aimed to (1) describe a systematic approach used to analyze and reduce CLABSI rates in a surgical ICU (SICU) at a quaternary care medical facility (CLABSI reduction bundle) and (2) examine the association of the bundle on CLABSI rates in the SICU, compared to six unexposed health system ICUs. METHODS: Retrospective analysis of 14,022 adult patients with > 0 central line days within a single health system in the southeastern United States. The CLABSI intervention bundle was created and implemented in July 2021. Single and multiple interrupted time series analyses were performed to assess the impact of the CLABSI bundle on CLABSI rate in SICU (compared to control ICUs) pre- and post-intervention. Secondary analyses examined the association of the bundle with ICU mortality and length of stay. RESULTS: The CLABSI bundle was associated with a significant immediate effect in reducing the CLABSI rate in the SICU compared with control ICUs. There was no significant change in the slope of CLABSI rate post-intervention, compared to control ICUs. There was no significant association of the CLABSI reduction bundle on ICU length of stay or mortality in the SICU. CONCLUSION: The CLABSI bundle was associated with an immediate reduction in CLABSI incidence in the SICU compared to unexposed ICUs. A simple, bundled intervention can be effective in reducing CLABSI incidence in a surgical ICU population.

When in the intensive care unit (ICU), many patients have different lines, drains, catheters, and other devices inserted into the body to help care for them. Each device has a risk of getting infected and can make a patient's hospital stay more complicated, longer, and require more intense treatments. One ICU at our health system performed a long-term quality improvement intervention to reduce and prevent these kinds of infections. Over the course of 4­6 months, multiple changes to daily patient care related to central lines were implemented. Our study examined the effects of this QI intervention. Using data from our ICU database, we determined that these changes decreased the number infections immediately after implementing them, but not over the long term. They also did not impact how long patients stayed in the hospital nor their risk of dying (mortality). These new protocols offer a way to reduce infections, and more work needs to be done to continue reducing them for patients in the ICU.

An Analysis of Outcomes Following a Central Line Associated Blood Stream Infections (CLABSI) Reduction Quality Improvement Project in a Tertiary Care Center.

Central Line Associated Blood Stream Infections (CLABSI) continue to be a significant complication for hospitalized patients. Hospitals have used various strategies to reduce CLABSI events due to the significant complications and associated costs. In this QI analysis, we examined the impact of a CLABSI reduction quality improvement project within a single ICU at a tertiary care medical center. Absolute CLABSI counts were compared between this ICU and other health system ICUs that did not implement the bundle. A sustained reduction in absolute CLABSI counts to or near zero was observed over 17 months after implementation. ICUs not performing the interventions during this time consistently reported ≥ 2 CLABSI per month. Further analysis is needed to assess causality and the generalizability of bundle components to other ICUs. These findings may provide other health systems with additional strategies to prevent CLABSI and provide consistent, evidence-based supportive care to critically ill patients.

Dental school quality assessment: Effect of student calibration on the outcomes of fixed prosthodontic cases.

BACKGROUND: Quality assurance (QA) of predoctoral dental student laboratory work is an essential part of the learning process that involves evaluating the student's ability, providing constructive feedback, helping develop the students' ability to self-assess, and promoting collegiality and communication among students, faculty, and laboratories. Faculty calibration, while often difficult to coordinate, is also necessary to providing consistent student feedback. AIM: The purpose of this study was to evaluate whether periodic calibration exercises with the fourth-year dental students and faculty impacted the number of student cases rejected during Quality Assurance evaluation of fixed prosthodontic cases submitted to The Dental College of Georgia laboratory tracking. CONCLUSION: Findings from this study provided evidence that ongoing calibration did result in a reduced number of incoming QA rejections in all periods reviewed except for one in which there was significant turnover among department faculty affecting QA calibration for that time period.

Enhanced port-wine stain lightening achieved with combined treatment of selective photothermolysis and imiquimod.

BACKGROUND: Pulsed dye laser (PDL) is the gold standard for treatment of port-wine stain (PWS) birthmarks but multiple treatments are required and complete resolution is often not achieved. Posttreatment vessel recurrence is thought to be a factor that limits efficacy of PDL treatment of PWS. Imiquimod 5% cream is an immunomodulator with antiangiogenic effects. OBJECTIVE: We sought to determine if application of imiquimod 5% cream after PDL improves treatment outcome. METHODS: Healthy individuals with PWS (n = 24) were treated with PDL and then randomized to apply posttreatment placebo or imiquimod 5% cream for 8 weeks. Chromameter measurements (Commission Internationale de l'Eclairage L∗a∗b∗ colorspace) for 57 PWS sites (multiple sites per patient) were taken at baseline and compared with measurements taken 8 weeks posttreatment. The Δa∗ (change in erythema) and ΔE (difference in color between normal-appearing skin and PWS skin) were measured to quantify treatment outcome. RESULTS: Two patients developed minor skin irritation. Other adverse effects were not noted. Average ∆a∗ was 0.43 for PDL + placebo sites (n = 25) and 1.27 for PDL + imiquimod sites (n = 32) (P value = .0294) indicating a greater reduction in erythema with imiquimod. Average ∆E was 2.59 for PDL + placebo and 4.08 for PDL + imiquimod (P value = .0363), again indicating a greater color improvement with imiquimod. LIMITATIONS: Effects were evaluated after a single treatment and duration of effect is unknown. CONCLUSION: Combined selective photothermolysis and antiangiogenic therapy may enhance PWS treatment efficacy.

Immunohistochemistry of angiogenesis mediators before and after pulsed dye laser treatment of angiomas.

BACKGROUND AND OBJECTIVE: Tissue effects of vascular lesion laser treatment are incompletely understood. Injury caused by pulsed dye laser (PDL) treatment may result in altered expression of mediators associated with angiogenesis. MATERIALS AND METHODS: Eight human subjects had one angioma treated with PDL (7 mm, 1.5 millisecond pulse duration, 9 J/cm(2), cryogen spray cooling of 30 millisecond with a 30 millisecond delay). One week later, three biopsies were taken: normal skin, untreated angioma, angioma post-PDL. Tissue was frozen and sections processed for immunohistochemistry staining of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase 9 (MMP-9), and angiopoietin 2 (ANG-2). Images were graded in a blinded fashion by a board certified dermatopathologist. RESULTS: There were no clear trends in VEGF expression in the epidermis, dermis, or endothelial cells. As compared to normal skin, angiomas demonstrated the following: bFGF was decreased in the epidermis; MMP-9 was decreased or unchanged in the epidermis and increased in the endothelial cells; ANG-2 was increased in the endothelial cells. When comparing normal skin to angiomas + PDL, bFGF was decreased in the epidermis and increased in the dermis; MMP-9 was decreased or unchanged in the epidermis; ANG-2 was again increased in the endothelial cells. Comparison of staining in angioma to angioma + PDL samples revealed increased dermal bFGF expression. CONCLUSION: Alterations in angiogenesis mediators were noted after PDL. Angiogenesis mediator changes associated with PDL treatment differed from those previously reported for incisional biopsies. This pilot study can guide future work on laser-induced alterations in vascular lesions and such information may ultimately be used to optimize treatment outcomes.

Characterization of single-nucleotide variation in Indian-origin rhesus macaques (Macaca mulatta).

BACKGROUND: Rhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs) in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies. RESULTS: We used the available rhesus macaque draft genome sequence, new sequence data from unrelated individuals and existing published sequence data to create a genome-wide SNP resource for Indian-origin rhesus monkeys. The original reference animal and two additional Indian-origin individuals were resequenced to low coverage using SOLiD™ sequencing. We then used three strategies to validate SNPs: comparison of potential SNPs found in the same individual using two different sequencing chemistries, and comparison of potential SNPs in different individuals identified with either the same or different sequencing chemistries. Our approach validated approximately 3 million SNPs distributed across the genome. Preliminary analysis of SNP annotations suggests that a substantial number of these macaque SNPs may have functional effects. More than 700 non-synonymous SNPs were scored by Polyphen-2 as either possibly or probably damaging to protein function and these variants now constitute potential models for studying functional genetic variation relevant to human physiology and disease. CONCLUSIONS: Resequencing of a small number of animals identified greater than 3 million SNPs. This provides a significant new information resource for rhesus macaques, an important research animal. The data also suggests that overall genetic variation is high in this species. We identified many potentially damaging non-synonymous coding SNPs, providing new opportunities to identify rhesus models for human disease.

Porokeratotic eccrine ostial and dermal duct nevus treated with a combination erbium/CO2 laser: a case and brief review.

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is an uncommon disease that presents early in childhood and is characterized by keratotic papules, often in a linear configuration. We describe a 12-year-old girl with characteristic lesions of PEODDN and describe her response to treatment with a combination CO2/Erbium laser. We also briefly review the literature on PEODDN.

Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis.

Endometriosis is a common chronic inflammatory condition causing pelvic pain and infertility in women, with limited treatment options and 50% heritability. We leveraged genetic analyses in two species with spontaneous endometriosis, humans and the rhesus macaque, to uncover treatment targets. We sequenced DNA from 32 human families contributing to a genetic linkage signal on chromosome 7p13-15 and observed significant overrepresentation of predicted deleterious low-frequency coding variants in NPSR1, the gene encoding neuropeptide S receptor 1, in cases (predominantly stage III/IV) versus controls (P = 7.8 × 10-4). Significant linkage to the region orthologous to human 7p13-15 was replicated in a pedigree of 849 rhesus macaques (P = 0.0095). Targeted association analyses in 3194 surgically confirmed, unrelated cases and 7060 controls revealed that a common insertion/deletion variant, rs142885915, was significantly associated with stage III/IV endometriosis (P = 5.2 × 10-5; odds ratio, 1.23; 95% CI, 1.09 to 1.39). Immunohistochemistry, qRT-PCR, and flow cytometry experiments demonstrated that NPSR1 was expressed in glandular epithelium from eutopic and ectopic endometrium, and on monocytes in peritoneal fluid. The NPSR1 inhibitor SHA 68R blocked NPSR1-mediated signaling, proinflammatory TNF-α release, and monocyte chemotaxis in vitro (P < 0.01), and led to a significant reduction of inflammatory cell infiltrate and abdominal pain (P < 0.05) in a mouse model of peritoneal inflammation as well as in a mouse model of endometriosis. We conclude that the NPSR1/NPS system is a genetically validated, nonhormonal target for the treatment of endometriosis with likely increased relevance to stage III/IV disease.

MicroRNA transcriptome in the newborn mouse ovaries determined by massive parallel sequencing.

Small non-coding RNAs, such as microRNAs (miRNAs), are involved in diverse biological processes including organ development and tissue differentiation. Global disruption of miRNA biogenesis in Dicer knockout mice disrupts early embryogenesis and primordial germ cell formation. However, the role of miRNAs in early folliculogenesis is poorly understood. In order to identify a full transcriptome set of small RNAs expressed in the newborn (NB) ovary, we extracted small RNA fraction from mouse NB ovary tissues and subjected it to massive parallel sequencing using the Genome Analyzer from Illumina. Massive sequencing produced 4 655 992 reads of 33 bp each representing a total of 154 Mbp of sequence data. The Pash alignment algorithm mapped 50.13% of the reads to the mouse genome. Sequence reads were clustered based on overlapping mapping coordinates and intersected with known miRNAs, small nucleolar RNAs (snoRNAs), piwi-interacting RNA (piRNA) clusters and repetitive genomic regions; 25.2% of the reads mapped to known miRNAs, 25.5% to genomic repeats, 3.5% to piRNAs and 0.18% to snoRNAs. Three hundred and ninety-eight known miRNA species were among the sequenced small RNAs, and 118 isomiR sequences that are not in the miRBase database. Let-7 family was the most abundantly expressed miRNA, and mmu-mir-672, mmu-mir-322, mmu-mir-503 and mmu-mir-465 families are the most abundant X-linked miRNA detected. X-linked mmu-mir-503, mmu-mir-672 and mmu-mir-465 family showed preferential expression in testes and ovaries. We also identified four novel miRNAs that are preferentially expressed in gonads. Gonadal selective miRNAs may play important roles in ovarian development, folliculogenesis and female fertility.

Fast, large area multiphoton exoscope (FLAME) for macroscopic imaging with microscopic resolution of human skin.

We introduce a compact, fast large area multiphoton exoscope (FLAME) system with enhanced molecular contrast for macroscopic imaging of human skin with microscopic resolution. A versatile imaging platform, FLAME combines optical and mechanical scanning mechanisms with deep learning image restoration to produce depth-resolved images that encompass sub-mm2 to cm2 scale areas of tissue within minutes and provide means for a comprehensive analysis of live or resected thick human skin tissue. The FLAME imaging platform, which expands on a design recently introduced by our group, also features time-resolved single photon counting detection to uniquely allow fast discrimination and 3D virtual staining of melanin. We demonstrate its performance and utility by fast ex vivo and in vivo imaging of human skin. With the ability to provide rapid access to depth resolved images of skin over cm2 area and to generate 3D distribution maps of key sub-cellular skin components such as melanocytic dendrites and melanin, FLAME is ready to be translated into a clinical imaging tool for enhancing diagnosis accuracy, guiding therapy and understanding skin biology.

Non-invasive optical biopsy by multiphoton microscopy identifies the live morphology of common melanocytic nevi.

Multiphoton microscopy (MPM) is a promising non-invasive imaging tool for discriminating benign nevi from melanoma. In this study, we establish a MPM morphologic catalogue of common nevi, information that will be critical in devising strategies to distinguish them from nevi that are evolving to melanoma that may present with more subtle signs of malignancy. Thirty common melanocytic nevi were imaged in vivo using MPM. Quantitative parameters that can distinguish between different types of nevi were developed and confirmed by examining the histology of eleven of the imaged nevi. MPM features of nevi examined included cytologic morphology of melanocytes in the epidermis and dermis, the size and distribution of nevomelanocytes both within and around nests, the size of rete ridges, and the presence of immune cells in the dermis. Distinguishing features include cytological morphology, the size of nevomelanocytes, the size of nevomelanocyte nests, and the distribution of nevomelanocytes. Notably, these distinguishing characteristics were not easily appreciated in fixed tissues, highlighting essential differences in the morphology of live skin. Taken together, this work provides a morphologic compendium of normal nevi, information that will be critical in future studies directed at identifying melanocytic nevi that are evolving to melanoma.

Population-Based Estimation of the Preterm Birth Rate in Lilongwe, Malawi: Making Every Birth Count.

Objective The objective of this study was to perform a population-based estimation of the preterm birth (PTB) rate in regions surrounding Lilongwe, Malawi. Study Design We partnered with obstetrician specialists, community health workers, local midwives, and clinicians in a 50 km region surrounding Lilongwe, Malawi, to perform a population-based estimation of the PTB rate during the study period from December 1, 2012 to May 19, 2015. Results Of the 14,792 births captured, 19.3% of births were preterm, including preterm early neonatal deaths. Additional PTB risk factors were similarly prevalent including domestic violence, HIV, malaria, anemia, and malnutrition. Conclusion When performing a population-based estimation of the rate of PTB, including women without antenatal care and women delivering at home, the 19.3% rate of PTB is among the highest recorded globally. This is accompanied by a high rate of risk factors and comorbid conditions.

Genetic Discrimination Between LADA and Childhood-Onset Type 1 Diabetes Within the MHC.

OBJECTIVE: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS: The strongest associations in the MHC class II region (rs3957146, ß [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (ß [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, ß [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.