UCHealth Yampa Valley Medical Center

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). SEARCH STRATEGY: We searched international scientific databases, trial registration websites, and references of identified articles. SELECTION CRITERIA: Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. DATA COLLECTION AND ANALYSIS: Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. MAIN RESULTS: Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97-1.4, vaginal progesterone RR 0.97; 95% CI 0.77-1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47-0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42-0.75). AUTHOR'S CONCLUSIONS: In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

This is the first of two significant assessments of the geological energy potential of the U.S. The second one is U.S.G.S. Circular 790. Systems analyzed include: Hydrothermal convection systems (with estimates of potential for many specific sites in the West), Igneous related systems (related to current or recent volcanism), Estimates of the conductive transport of heat in most areas of CONUS, Recovery of heat from molten igneous systems (magma), and Geopressured geothermal energy in the Gulf Coast area. The significance of this report is that it began to give policy makers a first handle on the quantities and qualities of geothermal energy in the ground in much of the U.S. Economics (costs and revenues) are not considered. (DJE - 2005)

STUDY DESIGN: Longitudinal Cohort Study. OBJECTIVE: Determine 1-year patient-reported outcomes associated with preoperative chronic opioid therapy and high-preoperative opioid dosages in patients undergoing elective spine surgery. SUMMARY OF BACKGROUND DATA: Back pain is the most disabling condition worldwide and over half of patients presenting for spine surgery report using opioids. Preoperative dosage has been correlated with poor outcomes, but published studies have not assessed the relationship of both preoperative chronic opioids and opioid dosage with patient-reported outcomes. METHODS: For patients undergoing elective spine surgery between 2010 and 2017, our prospective institutional spine registry data was linked to opioid prescription data collected from our state's Prescription Drug Monitoring Program to analyze outcomes associated with preoperative chronic opioid therapy and high-preoperative opioid dosage, while adjusting for confounders through multivariable regression analyses. Outcomes included 1-year meaningful improvements in pain, function, and quality of life. Additional outcomes included 1-year satisfaction, return to work, 90-day complications, and postoperative chronic opioid use. RESULTS: Of 2128 patients included, preoperative chronic opioid therapy was identified in 21% and was associated with significantly higher odds (adjusted odds ratio [95% confidence interval]) of not achieving meaningful improvements at 1-year in extremity pain (aOR:1.5 [1.2-2]), axial pain (aOR:1.7 [1.4-2.2]), function (aOR:1.7 [1.4-2.2]), and quality of life (aOR:1.4 [1.2-1.9]); dissatisfaction (aOR:1.7 [1.3-2.2]); 90-day complications (aOR:2.9 [1.7-4.9]); and postoperative chronic opioid use (aOR:15 [11.4-19.7]). High-preoperative opioid dosage was only associated with postoperative chronic opioid use (aOR:4.9 [3-7.9]). CONCLUSION: Patients treated with chronic opioids prior to spine surgery are significantly less likely to achieve meaningful improvements at 1-year in pain, function, and quality of life; and less likely to be satisfied at 1-year with higher odds of 90-day complications, regardless of dosage. Both preoperative chronic opioid therapy and high-preoperative dosage are independently associated with postoperative chronic opioid use. LEVEL OF EVIDENCE: 2.

PURPOSE: The purpose of this study was to gain a better understanding of what it means for adolescent females to live with type 1 diabetes. METHODS: Van Manen's phenomenological framework was used to guide the project of inquiry. Adolescents were recruited from a diabetes camp. A purposive sample of 10 adolescent females, aged 16 and 17 years, volunteered to participate in the study. Unstructured, one-on-one interviews were conducted and participants' accounts were transcribed and analyzed for themes. RESULTS: Five themes were identified: (1) blending in with the adolescent culture, (2) standing out and being watched, (3) weighing the options and making choices, (4) being tethered to the system and to diabetes, and (5) struggling with conflicts. These adolescent females struggled with several conflicts and choices they were forced to make on a daily basis. They felt tethered to a disease that would never go away and to the healthcare system. Yet, they adopted ways to handle their disease so that it was manageable within the context of their lives. Fitting in with their peers was often more important than diabetes management. CONCLUSIONS: Making visible the experience of adolescent females living with type 1 diabetes has implications for practice, education, and research in diabetes education.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is an important event that is diagnosed on head NCCT. Increased NCCT utilization in busy hospitals may limit timely identification of ICH. RAPID ICH is an automated hybrid 2D-3D convolutional neural network application designed to detect ICH that may allow for expedited ICH diagnosis. We determined the accuracy of RAPID ICH for ICH detection and ICH volumetric quantification on NCCT. MATERIALS AND METHODS: NCCT scans were evaluated for ICH by RAPID ICH. Consensus detection of ICH by 3 neuroradiology experts was used as the criterion standard for RAPID ICH comparison. ICH volume was also automatically determined by RAPID ICH in patients with intraparenchymal or intraventricular hemorrhage and compared with manually segmented ICH volumes by a single neuroradiology expert. ICH detection accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios by RAPID ICH were determined. RESULTS: = 0.983); the median absolute error was 3 mL. CONCLUSIONS: RAPID ICH is highly accurate in the detection of ICH and in the volumetric quantification of intraparenchymal and intraventricular hemorrhages.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by both structural abnormalities and inflammation in the brain. While recent research has chiefly focused on the structural changes involved in AD, understanding the pathophysiology and associated inflammation of the AD brain helps to elucidate potential therapeutic and preventative options. By exploring the data supporting an inflammatory etiology of AD, we present a case for the use of existing evidence-based treatments addressing inflammation as promising options for treating and preventing AD. We present data demonstrating tumor necrosis factor alpha association with the inflammation of AD. We also discuss data supporting TNF alpha associated inflammation in traumatic brain injury, stroke, and spinal disc associated radiculopathy. We augment this previously unarticulated concept of a unifying pathophysiology of central nervous system disease, with reports of benefits of TNF alpha inhibition in many hundreds of patients with those diseases, including AD. We also assess the pathophysiologic and clinical trial evidence supporting the role of other inflammation resolving treatments in AD. In aggregate, the data from the several potentially effective therapeutic and preventative options contained within this report presents a clearer picture of next steps needed in research of treatment alternatives.

This Bench Book summarizes theory, research, and a forensic assessment model of parental gatekeeping relevant for understanding and resolving child custody disputes. This concise format is geared primarily as a resource for judges, though it may be equally valuable to evaluators, parenting coordinators, and others. Gatekeeping encompasses a common statutory factor of support for the other parent–child relationship. The gatekeeping model includes a continuum ranging from facilitative to restrictive gatekeeping. Behavioral examples are presented. Implications of a gatekeeping analysis for crafting parenting plans are described, including in relocation cases and when there has been a history of intimate partner violence.

Metabolic effects of glucagon-like peptide 1 (GLP-1) receptor agonists are confounded by weight loss and not fully recapitulated by increasing endogenous GLP-1. We tested the hypothesis that GLP-1 receptor (GLP-1R) agonists exert weight loss-independent, GLP-1R-dependent effects that differ from effects of increasing endogenous GLP-1. Individuals with obesity and prediabetes were randomized to receive for 14 weeks the GLP-1R agonist liraglutide, a hypocaloric diet, or the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin. The GLP-1R antagonist exendin(9-39) and placebo were administered in a two-by-two crossover study during mixed-meal tests. Liraglutide and diet, but not sitagliptin, caused weight loss. Liraglutide improved insulin sensitivity measured by HOMA for insulin resistance (HOMA-IR), the updated HOMA model (HOMA2), and the Matsuda index after 2 weeks, prior to weight loss. Liraglutide decreased fasting and postprandial glucose levels, and decreased insulin, C-peptide, and fasting glucagon levels. In contrast, diet-induced weight loss improved insulin sensitivity by HOMA-IR and HOMA2, but not the Matsuda index, and did not decrease glucose levels. Sitagliptin increased endogenous GLP-1 and GIP values without altering insulin sensitivity or fasting glucose levels, but decreased postprandial glucose and glucagon levels. Notably, sitagliptin increased GIP without altering weight. Acute GLP-1R antagonism increased glucose levels in all groups, increased the Matsuda index and fasting glucagon level during liraglutide treatment, and increased endogenous GLP-1 values during liraglutide and sitagliptin treatments. Thus, liraglutide exerts rapid, weight loss-independent, GLP-1R-dependent effects on insulin sensitivity that are not achieved by increasing endogenous GLP-1. ARTICLE HIGHLIGHTS: Metabolic benefits of glucagon-like peptide 1 (GLP-1) receptor agonists are confounded by weight loss and are not fully achieved by increasing endogenous GLP-1 through dipeptidyl peptidase 4 (DPP-4) inhibition. We investigated weight loss-independent, GLP-1 receptor (GLP-1R)-dependent metabolic effects of liraglutide versus a hypocaloric diet or the DPP-4 inhibitor sitagliptin. GLP-1R antagonism with exendin(9-39) was used to assess GLP-1R-dependent effects during mixed meals. Liraglutide improved insulin sensitivity and decreased fasting and postprandial glucose prior to weight loss, and these benefits were reversed by exendin(9-39). GLP-1R agonists exert rapid, weight loss-independent, GLP-1R-dependent effects on insulin sensitivity not achieved by increasing endogenous GLP-1.

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies of such traits may focus on them as a single diagnostic entity or by analyzing specific components. For example, in orofacial clefting (OFC), three subtypes-cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a "cleft map" of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 [CP], WNT5A [CLP]), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.

Abstract Direct measurements of atmospheric sub‐3 nm particles are crucial for understanding the new particle formation mechanisms, but such measurements are very limited at present. We report measurements of sub‐3nm particles at Brookhaven, New York (a coastal site in summer) and Kent, Ohio (a continental site in winter). During daytime, in approximately 80% of the observation days at both sites, sub‐3nm particle events were observed with concentrations of 2800 ± 1600 cm‐ 3 , and they appeared with the elevated sulfuric acid concentrations. During the nighttime at the coastal site under the marine air mass influences, there were also substantial concentrations of sub‐3nm particles (1500 ± 400 cm‐ 3 ), but they did not grow larger. On the other hand, at the coastal Brookhaven site under the continental air mass influences and at the inland Kent site during the night, the sub‐3nm particles were significantly lower (190 ± 130 cm‐ 3 ). Our results indicate that sub‐3nm particles were not always present, and their presence was rather closely associated with specific aerosol nucleation precursors: sulfuric acid and other unknown condensable chemical species likely present in the marine air masses. These findings are thus different from other studies conducted in the Finland boreal forest, which showed a persistent presence of high concentrations of sub‐2nm particles and that these sub‐2nm particles were more correlated to monoterpene oxidation products than to sulfuric acid. Therefore, different nucleation mechanisms, as opposed on to a universal mechanism, involving different nucleation precursors dominate in different atmospheric environments with different emissions and transported trace gases.

BACKGROUND: The serum proteomic test VeriStrat has been shown to be able to classify advanced non-small cell lung cancer (NSCLC) patients for overall survival (OS) after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). In this study, VeriStrat was evaluated as a pre-treatment stratification tool in patients with advanced stage NSCLC for treatment with the combination of erlotinib and sorafenib, considering both OS and progression-free survival (PFS) as end points. METHODS: Serum samples from 50 patients treated within the context of a phase II trial of first-line erlotinib and sorafenib were analysed with VeriStrat, a fully locked mass spectrometry-based test that identifies patients likely to have good or poor outcome on EGFR therapy based on eight distinct features in mass spectra. Analysis was performed fully blinded to all clinical data, and then the outcome data were analysed with respect to the obtained serum classifications. RESULTS: VeriStrat classified pre-treatment samples into two groups, VeriStrat Good and VeriStrat Poor, which were significantly different in OS (hazard ratio (HR) 0.30, log-rank P=0.009) and in PFS (HR 0.40, log-rank P=0.035). CONCLUSION: VeriStrat has shown its potential for stratification of unselected, advanced stage NSCLC patients treated in first line with a combination of erlotinib and sorafenib.

AIM: To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms. MATERIALS AND METHODS: Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled. Measurements were made at baseline, after 2 weeks prior to significant weight loss and after 14 weeks. The primary outcomes were measures of endothelial function: flow-mediated vasodilation (FMD), plasminogen activator inhibitor-1 (PAI-1) and urine albumin-to-creatinine ratio (UACR). RESULTS: Eighty-eight individuals were studied (liraglutide N = 44, diet N = 22, sitagliptin N = 22). Liraglutide and diet reduced weight, insulin resistance and PAI-1, while sitagliptin did not. There was no significant effect of any treatment on endothelial vasodilator function measured by FMD. Post hoc subgroup analyses in individuals with baseline FMD below the median, indicative of greater endothelial dysfunction, showed an improvement in FMD by all three treatments. GLP-1R antagonism with exendin (9-39) increased fasting blood glucose but did not change FMD or PAI-1. There was no effect of treatment on UACR. Finally, liraglutide, but not sitagliptin or diet, reduced the chemokine monocyte chemoattractant protein-1 (MCP-1). CONCLUSION: Liraglutide and diet reduce weight, insulin resistance and PAI-1. Liraglutide, sitagliptin and diet do not change FMD in obese individuals with prediabetes with normal endothelial function. Liraglutide alone lowers the pro-inflammatory and pro-atherosclerotic chemokine MCP-1, indicating that this beneficial effect is independent of weight loss.

We aimed to identify and describe the current interventions used in preoperative programs ("prehabilitation") for spine surgery. Knowledge gaps in approaches, feasibility, timing, patient experience, clinical outcomes, and health care costs were explored while describing their potential benefits on physical and psychological outcomes. An electronic search was conducted from January 2004 to February 2022 in Ovid Medline, Embase, EBSCO CINAHL, the Cochrane Database of Systematic Reviews, and PEDro to identify studies in English evaluating adults enrolled in prehabilitation before undergoing elective spine surgeries. Studies were uploaded into DistillerSR for systematic screening after removing duplicates. Four reviewers screened nested references for inclusion based on titles and abstracts, followed by their full-text review. Two reviewers subsequently extracted data and summarized the results. The results were reported using Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. Studies were rated for quality using National Health and Medical Research Council criteria. Out of 18,879 potential studies, a total of 23 studies (0.12%) met the eligibility criteria and were included in this scoping review. The prehabilitation programs included general education (n = 6, 26%), exercise (n = 6, 26%), cognitive behavioral therapy (n = 3, 13%), pain neuroscience education (n = 3, 13%), health behavior counseling (n = 3, 13%), and mindfulness (n = 2, 9%). Additional studies are needed to identify optimal patient characteristics, intervention dosage, and whether multimodal approaches using a combination of physical and psychological strategies lead to more favorable outcomes. Although studies on prehabilitation for spine surgery are limited, they seem to demonstrate that prehabilitation programs are feasible, reduce medical expenditures, and improve patients' postoperative pain, disability, self-efficacy, psychological behaviors, and satisfaction with surgical outcomes. The available literature suggests there is an opportunity to improve patient experience, clinical outcomes and reduce medical costs with the use of prehabilitation in spine surgery.

This paper explores the viewpoint that, as a group, adolescents with diabetes are oppressed by health care professionals who use approaches to diabetes care delivery that are paternalistic in nature. These approaches can lead to negative health/diabetes outcomes in this age group. As inherent in oppressed group characteristics, adolescents with diabetes may not realize that they are being treated unfairly or that they have rights as patients. Nurses are in a unique position to advocate for these adolescents and to help them become advocates for themselves.

Environmental context The organic fraction of atmospheric aerosols is a complex mixture of thousands of species, which play an important role in many atmospheric processes, such as absorbing and scattering solar radiation. We analysed the water-soluble organic fraction of ambient aerosol samples, and quantified over 45 carboxylic acids, sugars, sugar anhydrides and sugar alcohols. The presence of fairly high concentrations of sugars and sugar-alcohols suggests a significant biological input (e.g. pollen, fungi and bacteria) to the water-soluble organic fraction of non-urban aerosols. Abstract Water-soluble organic constituents of PM2.5 aerosol (particulate matter with an aerodynamic diameter =2.5 µm) have not been well characterised so far. The goal of this work was to perform quantitative analysis of individual water-soluble organic species in aerosol samples collected in July of 2010 at the Storm Peak Laboratory (3210 m above sea level) located in the Colorado Park Range (Steamboat Springs, CO, USA). Aqueous extracts were combined into six composites and analysed for organic carbon (OC), water-soluble organic carbon (WSOC), water-insoluble OC, inorganic ions, organic acids, lignin derivatives, sugar-alcohols, sugars and sugar-anhydrates. Analysis of higher molecular weight water-soluble organics was done using ultrahigh resolution mass spectrometry. Approximately 2400 positive and 4000 negative ions were detected and assigned to monoisotopic molecular formulae in the mass range of 100–800 Da. The higher number of negative ions reflects a predominant presence of highly oxidised organic compounds. Individual identified organic species represented up to 30 % of the water-soluble organic mass (WSOM). The WSOM fractions of the low molecular weight organic acids, sugars and sugar alcohols were 3–12 %, 1.0–16 % and 0.4–1.9 %. Significant amounts of arabitol, mannitol and oxalic acid are most likely associated with airborne fungal spores and conidia that were observed on the filters using high resolution electron microscopy. Overall, higher concentrations of sugars (glucose, sucrose, fructose etc.) in comparison with biomass burning tracer levoglucosan indicate that a significant mass fraction of WSOC is related to airborne biological species.

An integrative conceptual framework and forensic evaluation model are presented for custody evaluators when the issue of Intimate Partner Violence is salient in a child custody case (IPV-CC). A revised typology of IPV combines previously proposed categories with a violence risk assessment approach to reflect both the descriptive and predictive functions for evaluators. It is a research-based forensic model. Continuous and categorical variable approaches to the analysis of IPV in custody cases are presented and contrasted. Ten behavioral dimensions of IPV-CC are described to serve as a multidimensional behavioral grid approach to the assessment of IPV. The integrated framework and perspective allows for greater behavioral specificity in the analysis. It avoids problems inherent in forensic assessment by subtype labeling. The court will be better informed by a multidimensional and continuous variable approach that provides behavioral versus categorical differentiation. This approach allows for more accurate and efficient risk communications to the court and translation to parenting plan recommendations. Issues involved with the forensic assessment of IPV in the custody context and making predictions/ recommendations about future parenting, co-parenting, and child adjustment are discussed.

To consolidate our understanding of "trigonitis" and its relevance in current urologic practice, we reviewed the literature on this entity. The MEDLINE, EMBASE, and Cochrane databases (1905 to present) were systematically reviewed for any English language articles addressing the following terms: trigonitis, cystitis trigoni, cystitis cystica, squamous metaplasia, pseudomembranous trigonitis, vaginal metaplasia, infection or inflammation of the trigone, and trigonitis in recurrent urinary tract infections (rUTI). Abstracts or articles not focused on trigonitis, or those only repeating findings from other original articles on trigonitis, and studies in children or men were excluded. Reported histologic findings on trigonitis, theories regarding its pathophysiology, and therapeutic strategies were reviewed. From 57 relevant articles, only 27 focused on trigonitis. Cystoscopic evaluation of the trigone described inflammatory lesions of cystitis cystica, occasionally small stones or pus-filled lesions, an appearance that should be differentiated from white patches of squamous metaplasia. Embryologic formation of the trigone, history of rUTIs, and effects of hormones on the trigone have been proposed as underlying pathophysiologic mechanisms. Numerous therapeutic strategies have been reported to treat symptomatic trigonitis, including antibiotic therapy, intravesical instillation of different agents, electrofulguration, and laser coagulation. However, no treatment indication criteria have been well established so far, and long-term data are lacking. Despite several reports describing histologic and endoscopic findings of trigonitis, its prevalence, pathophysiology, and treatment have remained poorly defined. Its relevance in the management of rUTIs should be further evaluated.

Telephone triage, or telephone advice counseling, is becoming a key managed care point-of-entry tool for patients and health plan members accessing the health system. Telephone triage functions as a logical front-end for health plans, integrated physician groups, or integrated delivery systems that want to shift their managed care efforts toward demand management. Key components of telephone triage include patient education, patient information, and guided access to appropriate care. Telephone triage generally requires 24-hour staffing by registered nurses and a computer software package based on either clinical protocols or clinical algorithms. Organizations can either install an in-house system or purchase this service from a vendor, health plan, or another provider. The decision to develop a telephone triage service in-house or to out-source it is determined largely by volume and the user's strategy for moving to successive levels of risk management.

All in-text\treferences\tunderlined\tin\tblue\tare\tlinked\tto\tpublications\ton\tResearchGate, letting you\taccess\tand\tread\tthem\timmediately.

Nonsyndromic orofacial clefts (OFCs) are among the most common craniofacial birth defects worldwide, and known to exhibit phenotypic and genetic heterogeneity. Cleft lip plus cleft palate (CLP) and cleft lip only (CL) are commonly combined together as one phenotype (CL/P), separately from cleft palate alone. In comparison, our study analyzes CL and CLP separately. A sample of 2218 CL and CLP cases, 4537 unaffected relatives of cases, and 2673 pure controls with no family history of OFC were selected from the Pittsburgh Orofacial Cleft (Pitt-OFC) multiethnic study.genome-wide association studies were run for seven specific phenotypes created based on the cleft type(s) observed within these families, as well as the combined CL/P phenotype. Five novel genome-wide significant associations, 3q29 (rs62284390), 5p13.2 (rs609659), 7q22.1 (rs6465810), 19p13.3 (rs628271), and 20q13.33 (rs2427238), and nine associations (p ≤ 1.0E-05) within previously confirmed OFC loci-PAX7, IRF6, FAM49A, DCAF4L2, 8q24.21, ARID3B, NTN1, TANC2 and the WNT9B:WNT3 gene cluster-were observed. We also found that single nucleotide polymorphisms within a subset of the associated loci, both previously known and novel, differ substantially in terms of their effects across cleft- or family-specific phenotypes, indicating not only etiologic differences between CL and CLP, but also genetic heterogeneity within each of the two OFC subtypes.