Dating archaeobotanical remains: a cautionary tale from Port au Choix,Newfoundland

In this paper we report on the first ¹⁴C dated archaeological seeds from the island of Newfoundland, Canada. Ninety-three archaeobotanical specimens were recovered from a midden deposit adjacent to a small dwelling at Point Riche (EeBi-20), a large Dorset Palaeoeskimo site near Port au Choix, northwestern Newfoundland. These remains were collected from a seemingly secure context within the midden, but AMS ¹⁴C testing of a sample of specimens produced modern ¹⁴C dates, indicating that the remains are intrusive to the Dorset occupation. While the majority of Newfoundland-based research assumes antiquity of archaeobotanical remains, we recommend using AMS ¹⁴C dating and other proxy data in future archaeobotanical studies to confirm antiquity prior to making interpretations regarding human–plant interactions.     

The late Pleistocene cultures of South America

Important to an understanding of the first peopling of any continent is an understanding of human dispersion and adaptation and their archeological signatures. Until recently, the earliest archeological record of South America was viewed uncritically as a uniform and unilinear development involving the intrusion of North American people who brought a founding cultural heritage, the fluted Clovis stone tool technology, and a big-game hunting tradition to the southern hemisphere between 11,000 and 10,000 years ago.^1–3 Biases in the history of research and the agendas pursued in the archeology of the first Americans have played a major part in forming this perspective.^4–6 Despite enthusiastic acceptance of the Clovis model by a vast majority of archeologists, several South American specialists have rejected it.^6–11 They contend that the presence of archeological sites in Tierra del Fuego and other regions by at least 11,000 to 10,500 years ago was simply insufficient time for even the fastest migration of North Americans to reach within only a few hundred years. Despite this concern, and despite the discovery of several pre-Clovis sites in South America,^6,10–12 some specialists^2,3 keep the Clovis model alive. Proponents of the model claim that the pre-Clovis sites are unreliable due to questionable radiocarbon dates, artifacts, and stratigraphy. Solid evidence at the Monte Verde site in Chile^14–16 and other localities^6,8,10–12 now indicates that South America was discovered by humans at least 12,500 years ago. How much earlier than 12,500 years ago is still a matter of conjecture.^6,10,12,15 Some proponents prefer a long chronology of 20,000 to 45,000 years ago,⁸ while others advocate a short chronology of 15,000 to 20,000 years ago^10–12 or only 11,000 years ago.^1–3. © 1999 Wiley-Liss, Inc.     

Common biological networks underlie genetic risk for alcoholism in African‐ and European‐American populations

Alcohol dependence (AD) is a heritable substance addiction with adverse physical and psychological consequences, representing a major health and economic burden on societies worldwide. Genes thus far implicated via linkage, candidate gene and genome‐wide association studies (GWAS) account for only a small fraction of its overall risk, with effects varying across ethnic groups. Here we investigate the genetic architecture of alcoholism and report on the extent to which common, genome‐wide SNPs collectively account for risk of AD in two US populations, African‐Americans (AAs) and European‐Americans (EAs). Analyzing GWAS data for two independent case–control sample sets, we compute polymarker scores that are significantly associated with alcoholism (P = 1.64 × 10^–3 and 2.08 × 10^–4 for EAs and AAs, respectively), reflecting the small individual effects of thousands of variants derived from patterns of allelic architecture that are population specific. Simulations show that disease models based on rare and uncommon causal variants (MAF < 0.05) best fit the observed distribution of polymarker signals. When scoring bins were annotated for gene location and examined for constituent biological networks, gene enrichment is observed for several cellular processes and functions in both EA and AA populations, transcending their underlying allelic differences. Our results reveal key insights into the complex etiology of AD, raising the possibility of an important role for rare and uncommon variants, and identify polygenic mechanisms that encompass a spectrum of disease liability, with some, such as chloride transporters and glycine metabolism genes, displaying subtle, modifying effects that are likely to escape detection in most GWAS designs.     

Diet,society, and economy in late medieval Spain: Stable isotope evidence from Muslims and Christians from Gandía,Valencia

This article investigates the diets of neighboring Christians and Muslims in late medieval Spain (here 13th–16th centuries) through the analysis of the stable isotopes of carbon (δ¹³C) and nitrogen (δ¹⁵N) in adult human and animal bone collagen. Twenty‐four Christians and 20 Muslims are sampled from two adjacent and contemporaneous settlements in the township of Gandía on the Mediterranean coast, together with the remains of 24 animals. Statistical differences in both δ¹³C and δ¹⁵N reveal that the diets of the two faith communities differed, despite living side‐by‐side. These differences may relate to inequalities in their access to foodstuffs, particularly to C₃/C₄ grain and/or possibly terrestrial meat sources, though cultural preferences are also highlighted. Isotopic values for animals were also found to vary widely, both between and within species, and this provides a window into the local livestock economy. Am J Phys Anthropol 156:263–273, 2015. © 2014 The Authors. American Journal of physical Anthropology published by Wiley Periodicals,Inc.     

Skin Responses to Ultraviolet Radiation: Effects of Constitutive Pigmentation,Sex, and Ancestry

Constitutive skin pigmentation and skin responses to ultraviolet radiation were measured on a sample of volunteers (n=250) living in State College, PA, USA. The sample was composed of individuals of European American (n=190), Hispanic (n=45), and East Asian ancestry (n=15). Constitutive pigmentation was measured using the Adjusted Melanin Index (AMI), Erythemal Dose Response (EDR) was measured using the slope of a* at 24 h (Δa*), and Melanogenic Dose–Response (MDR) was measured using ΔAM, the slope of AMI at 7 d. The relationships between constitutive skin pigmentation, EDR, MDR, sex, age, and ancestry were investigated. European Americans showed a lower constitutive pigmentation, had a significantly higher burn response (EDR), and had a significantly lower tanning response (MDR) than Hispanics and East Asians. No significant difference is seen between Hispanics and East Asians for either constitutive pigmentation or EDR. Constitutive pigmentation in females was slightly lower than in males in all three samples, but the difference was not significant. While no differences were observed in MDR between sexes, males had a stronger EDR than females regardless of population or constitutive pigmentation level, and this difference was significant in European Americans and Hispanics. We observed no age‐related differences in any of the populations or measures investigated. We evaluated the relationship between constitutive pigmentation, EDR and MDR. There was a strong inverse correlation between constitutive pigmentation and EDR in the three samples (European Americans, R²=0.176, P < 0.001; Hispanics, R²=0.204, P=0.009; East Asians, R²=0.223, P=0.098) and a strong direct correlation between constitutive pigmentation and MDR in European Americans and Hispanics (European Americans, R²=0.094, P < 0.001; Hispanics, R²=0.164, P=0.012). In other words, persons with lower constitutive pigmentation both burn more and tan less than persons with higher pigmentation. However, after controlling for constitutive pigmentation, EDR and MDR were significantly correlated in European Americans (R²=0.041 P=0.006). Thus, the general observation that persons who burn more tan less is probable because of the common link that these two phenotypes have with constitutive skin pigmentation and, in fact, once pigmentation has been adjusted for, there is a positive correlation between tanning response and burning response in European Americans.     

Lipid-dissolved γ-carotene, β-carotene,and lycopene in globular chromoplasts of peach palm (Bactris gasipaes Kunth) fruits

Main conclusion

High levels of β-carotene, lycopene, and the rare γ-carotene occur predominantly lipid-dissolved in the chromoplasts of peach palm fruits. First proof of their absorption from these fruits is reported. The structural diversity, the physical deposition state in planta, and the human bioavailability of carotenoids from the edible fruits of diverse orange and yellow-colored peach palm (Bactris gasipaes Kunth) varieties were investigated. HPLC–PDA–MSⁿ revealed a broad range of carotenes, reaching total carotenoid levels from 0.7 to 13.9 mg/100 g FW. Besides the predominant (all-E)-β-carotene (0.4–5.4 mg/100 g FW), two (Z)-isomers of γ-carotene (0.1–3.9 mg/100 g FW), and one (Z)-lycopene isomer (0.04–0.83 mg/100 g FW) prevailed. Approximately 89–94 % of total carotenoid content pertained to provitamin A carotenoids with retinol activity equivalents ranging from 37 to 609 µg/100 g FW. The physical deposition state of these carotenoids in planta was investigated using light, transmission electron, and scanning electron microscopy. The plastids found in both orange and yellow-colored fruit mesocarps were amylo-chromoplasts of the globular type, containing carotenoids predominantly in a lipid-dissolved form. The hypothesis of lipid-dissolved carotenoids was supported by simple solubility estimations based on carotenoid and lipid contents of the fruit mesocarp. In our study, we report first results on the human bioavailability of γ-carotene, β-carotene, and lycopene from peach palm fruit, particularly proving the post-prandial absorption of the rarely occurring γ-carotene. Since the physical state of carotenoid deposition has been shown to be decisive for carotenoid bioavailability, lipid-dissolved carotenoids in peach palm fruits are expected to be highly bioavailable, however, further studies are required.     

The Early Aurignacian human remains from La Quina-Aval (France)

There is a dearth of diagnostic human remains securely associated with the Early Aurignacian of western Europe, despite the presence of similarly aged early modern human remains from further east. One small and fragmentary sample of such remains consists of the two partial immature mandibles plus teeth from the Early Aurignacian of La Quina-Aval, Charente, France. The La Quina-Aval 4 mandible exhibits a prominent anterior symphyseal tuber symphyseos on a vertical symphysis and a narrow anterior dental arcade, both features of early modern humans. The dental remains from La Quina-Aval 1 to 4 (a dm₁, 2 dm₂, a P⁴ and a P₄) are unexceptional in size and present occlusal configurations that combine early modern human features with a few retained ancestral ones. Securely dated to ∼33 ka ¹⁴C BP (∼38 ka cal BP), these remains serve to confirm the association of early modern humans with the Early Aurignacian in western Europe.     

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by ³²P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35–0.90), higher GSH levels (+1.87 μmol GSH g^?1 haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38–2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84–1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.     

Associations of Body Mass and Body Fat Distribution with Parity Among African-American and Caucasian Women: The CARDIA Study

Associations of parity with body fat and its distribution are poorly understood; therefore, we examined the relationships between parity and obesity in young adult women. Body mass index (BMI), skin folds, and waist-hip ratio were compared in 1452 African-American and 1268 Caucasian nonpregnant women aged 18 to 30, adjusting for age (where no age-parity interactions were present), education, physical activity (assessed by questionnaire) and fitness (assessed by graded exercise test), dietary fat intake, alcohol and smoking. Adjusted mean BMI was significantly higher in African-American women aged 25–30 years with three or more children (28.5 kg/m²) than in those with two (27.0 kg/m²), one (26.2 kg/m²), or no children (26.3 kg/m²). Similar trends were found in Caucasians (BMI = 23.3, 23.4, 23.7, 25.0 kg/m² for parity = 0,1, 2, ≥ 3, respectively), but the mean BMI was significantly higher in African Americans in each parity group. The association between BMI and parity was not present among women 18–24 years of age. Skinfolds were directly associated with parity in African Americans only. Waist-hip ratios were generally lower among nulliparous than parous women in both ethnic groups; race differences were present only among nulliparas. In conclusion, parity was associated with BMI in women aged 25 to 30 years but did not explain ethnicity-related differences in body mass.     

Relationships of BMI to Cardiovascular Risk Factors Differ by Ethnicity

The burden of cardiovascular risk associated with obesity disproportionately affects African Americans and little is known about ethnic/racial differences in the relationship of obesity to cardiometabolic risk. This report assesses whether obesity is similarly associated with cardiometabolic risk factors in African Americans and whites of European ancestry. Cross‐sectional observational data from the Jackson Heart Study (JHS) and the Framingham Heart Study (FHS) were compared. This analysis uses participants aged 35–74 years with BMI >18.5 kg/m², and free of prevalent cardiovascular disease (CVD), from the initial JHS clinical examination (2000–2004) and the FHS Offspring (1998–2001) and Third Generation (2002–2005) cohorts. Participants were evaluated for the presence of lipid abnormalities, hypertension, and diabetes. Overall, 4,030 JHS (mean age 54 years, 64% women) and 5,245 FHS (mean age 51 years, 54% women) participants were available for analysis. The prevalence of all risk factors except high triglycerides and low high‐density lipoprotein (HDL) was substantially higher in JHS (all P < 0.001) and BMI was associated with increasing prevalence of most CVD risk factors within each race. For diabetes mellitus, hypertension, and low HDL, steeper relationships to BMI were observed in FHS than in JHS (P values <0.001–0.016). There were larger proportional increases in risk factor prevalence with increasing BMI in whites than in African Americans. The higher prevalence rates of cardiometabolic risk factors at nearly all levels of BMI in African Americans, however, suggest that additional factors contribute to the burden of CVD risk in African Americans.     

Pleistocene peopling of the Americas

Our species colonized North and South America last of all the major land masses, thereby ending the spread that began a million years earlier when ancestral members of the genus Homo first ventured out of Africa. But who were the first Americans? When did they arrive? Did they come in one migration or many? How quickly and by what adaptive strategies did they move across the environmentally diverse and trackless New World? How do they relate to contemporary native Americans? We have plenty of answers to these questions. Unfortunately, we can't agree which ones are right. This much is certain: the first Americans were Homo sapiens who came from northeast Asia via the Bering Straits (Fig. 1). They may have walked from Siberia to Alaska across Beringia, the land bridge formed when vast Pleistocene glaciers froze 5% of the world's water,¹ lowering global sea levels and exposing the shallow continental shelf between Asia and America. These hunter-gatherers were present throughout the Americas by 11,500 years ago, in time to witness the climatic and ecological changes, including the extinction of thirty-five genera of megafauna, that signalled the end of the Pleistocene. Beyond those bare facts there is controversy. Here, then, is a brief summary of the state of the argument over the peopling of the Americas.     

Initiation of Cellulose Biosynthesis

IN spite of much investigation the problem of the molecular mechanism of cellulose synthesis remains unsolved¹. Hexose phosphates², sugar nucleotides^3–6 and a glycolipid^7–9 have been suggested as the precursor of cellulose. Implicit in all these investigations is the supposition that a single substrate suffices for the synthesis. We describe here some preliminary observations which seem to throw new light on the possible mechanism.     

Analysis of coding variants identified from exome sequencing resources for association with diabetic and non-diabetic nephropathy in African Americans

Prior studies have identified common genetic variants influencing diabetic and non-diabetic nephropathy, diseases which disproportionately affect African Americans. Recently, exome sequencing techniques have facilitated identification of coding variants on a genome-wide basis in large samples. Exonic variants in known or suspected end-stage kidney disease (ESKD) or nephropathy genes can be tested for their ability to identify association either singly or in combination with known associated common variants. Coding variants in genes with prior evidence for association with ESKD or nephropathy were identified in the NHLBI-ESP GO database and genotyped in 5,045 African Americans (3,324 cases with type 2 diabetes associated nephropathy [T2D-ESKD] or non-T2D ESKD, and 1,721 controls) and 1,465 European Americans (568 T2D-ESKD cases and 897 controls). Logistic regression analyses were performed to assess association, with admixture and APOL1 risk status incorporated as covariates. Ten of 31 SNPs were associated in African Americans; four replicated in European Americans. In African Americans, SNPs in OR2L8, OR2AK2, C6orf167 (MMS22L), LIMK2, APOL3, APOL2, and APOL1 were nominally associated (P = 1.8 × 10^?4–0.044). Haplotype analysis of common and coding variants increased evidence of association at the OR2L13 and APOL1 loci (P = 6.2 × 10^?5 and 4.6 × 10^?5, respectively). SNPs replicating in European Americans were in OR2AK2, LIMK2, and APOL2 (P = 0.0010-0.037). Meta-analyses highlighted four SNPs associated in T2D-ESKD and all-cause ESKD. Results from this study suggest a role for coding variants in the development of diabetic, non-diabetic, and/or all-cause ESKD in African Americans and/or European Americans.     

Resemblance for Body Mass Index in Families of Obese African American and European American Women

Objective: We determined the levels of resemblance in body mass index (BMI) in large samples of families selected through obese African American and European American women. Research Methods and Procedures: We examined correlations among relatives in 1185 European American and African American families ascertained through age-matched obese women (BMI ≥ 30 kg/m²). A subset of 801 families were ascertained through extremely obese women (BMI ≥ 40 kg/m²). Results: Parent-offspring and sibling correlations ranged from 0.19 to 0.15, suggesting a moderate level of heritability in both groups. Mean BMI values for female relatives were lower for European Americans than for African Americans even though probands were matched, perhaps because the European American relatives regress to a lower population mean. We found significantly higher family correlations for height in European Americans, suggesting greater environmental variability among African Americans for factors affecting growth and physical development. Discussion: Our results suggest a similar level of heritability of BMI in families of obese African American and European American women. Other genetic studies will be needed to determine the extent to which the same or different genes and environmental conditions contribute to an overall similar heritability in the two racial groups.     

Obesity and C-reactive protein levels among white, black, and hispanic US adults

Objective: Studies suggest that obesity's adverse impact on cardiovascular mortality may be reduced in African Americans relative to white Americans. We examined whether obesity's association with novel cardiovascular risk factors such as C‐reactive protein (CRP) also varies by race and ethnicity. Methods and Procedures: We analyzed data from 10,492 white, African‐American, and Hispanic‐American participants of the 1999–2004 National Health and Nutrition Examination Survey, who were aged 20 years and older, with a BMI ≥18.5 kg/m² and CRP ≤10 mg/l. We fit sex‐specific multivariable models of the association of BMI or waist circumference with log CRP levels and tested for interactions of BMI or waist circumference with race/ethnicity. Results: Higher BMI was significantly associated with higher CRP in all racial/ethnic groups for both men and women (P > 0.05 for BMI–race/ethnicity interaction) before and after adjustment for age, education, and health behaviors. Larger waist circumference was also associated with higher CRP levels in all racial/ethnic groups before and after adjustment; among women, the relationship was strongest for Mexican Hispanics (P < 0.01 for waist circumference–race/ethnicity interaction). Results were similar after additional adjustment for medications that might affect CRP levels. Discussion: The association between obesity and CRP is at least as strong in African Americans and Hispanic Americans as in white Americans. Racial differences in the relationship between obesity and cardiovascular mortality are unlikely to be due to racial differences in obesity's impact on CRP.     

Palaeodiet reconstruction in a woman with probable celiac disease: A stable isotope analysis of bone remains from the archaeological site of Cosa (Italy)

Stable isotope analysis in the reconstruction of human palaeodiets can yield clues to early human subsistence strategies, origins and history of farming and pastoralist societies, and intra‐ and intergroup social differentiation. In the last 10 years, the method has been extended to the pathological investigation. Stable isotope analysis to better understand a diet‐related disease: celiac disease in ancient human bones was carried out. To do this, we analyzed the nitrogen and carbon isotopic composition of human (n = 37) and faunal (n = 8) bone remains from the archaeological site of Cosa at Ansedonia, on the Tyrrhenian coast near Orbetello (Tuscany), including the skeletal remains of a young woman (late 1st century–early 2nd century Common Era [CE]) with morphological and genetic features suggestive of celiac disease. We compared the young woman's isotopic data with those of other individuals recovered at the same site but from two later time periods (6th century CE; 11–12th century CE) and with literature data from other Italian archaeological sites dating to the same period. Her collagen δ¹³C and δ¹⁵N values differed from those of the samples at the same site, and from most but not all of the contemporary sites. Although the woman's diet appears distinct, chronic malnutrition resulting from severe malabsorption of essential nutrients due to celiac disease may have affected the isotopic composition of her bone collagen. Am J Phys Anthropol 154:349–356, 2014. © 2014 Wiley Periodicals, Inc.     

A genome-wide association study of severe teenage acne in European Americans

Despite the family aggregation of severe teenage acne, the genetic basis of this common skin condition remains unclear. We conducted a genome-wide association study (GWAS) on severe teenage acne in 928 European Americans. The SNP rs4133274 on chromosome 8q24 (72 kb upstream of MYC) revealed the most significant association with severe teenage acne (p value = 1.7 × 10^?6). The variant allele of this SNP (G allele) was associated with an increased risk of severe teenage acne with odds ratio of 4.01 (95 % confidence interval = 2.37–6.82). Upon further replication, our findings suggest new genetic basis of acne and may explain the association between acne and cancer risk observed in the epidemiological studies.     

Morphological Transformation of Human Astrocytes by Visna Virus with Complete Virus Production

VISNA, a medium-sized RNA virus, is comparable in mode of maturation and a number of other properties with the RNA tumour viruses^1,2. The virion also carries RNA-dependent DNA polymerase^3–5. This enzyme was first discovered in RNA tumour viruses and thought perhaps unique to them^6–9; but it was subsequently found in a very few other RNA viruses^3,10, where tumorigenicity was not a known attribute. The question whether RNA-dependent DNA polymerase is a hallmark of malignancy therefore remains entirely open.     

Reduced Neutrophil Count in People of African Descent Is Due To a Regulatory Variant in the Duffy Antigen Receptor for Chemokines Gene

Persistently low white blood cell count (WBC) and neutrophil count is a well-described phenomenon in persons of African ancestry, whose etiology remains unknown. We recently used admixture mapping to identify an approximately 1-megabase region on chromosome 1, where ancestry status (African or European) almost entirely accounted for the difference in WBC between African Americans and European Americans. To identify the specific genetic change responsible for this association, we analyzed genotype and phenotype data from 6,005 African Americans from the Jackson Heart Study (JHS), the Health, Aging and Body Composition (Health ABC) Study, and the Atherosclerosis Risk in Communities (ARIC) Study. We demonstrate that the causal variant must be at least 91% different in frequency between West Africans and European Americans. An excellent candidate is the Duffy Null polymorphism (SNP rs2814778 at chromosome 1q23.2), which is the only polymorphism in the region known to be so differentiated in frequency and is already known to protect against Plasmodium vivax malaria. We confirm that rs2814778 is predictive of WBC and neutrophil count in African Americans above beyond the previously described admixture association (P=3.8×10⁻⁵), establishing a novel phenotype for this genetic variant.     

Sleep assessment in a population-based study of chronic fatigue syndrome

Background

Chronic fatigue syndrome (CFS) is a disabling condition that affects approximately 800,000 adult Americans. The pathophysiology remains unknown and there are no diagnostic markers or characteristic physical signs or laboratory abnormalities. Most CFS patients complain of unrefreshing sleep and many of the postulated etiologies of CFS affect sleep. Conversely, many sleep disorders present similarly to CFS. Few studies characterizing sleep in unselected CFS subjects have been published and none have been performed in cases identified from population-based studies.

Methods

The study included 339 subjects (mean age 45.8 years, 77% female, 94.1% white) identified through telephone screen in a previously described population-based study of CFS in Wichita, Kansas. They completed questionnaires to assess fatigue and wellness and 2 self-administered sleep questionnaires. Scores for five of the six sleep factors (insomnia/hypersomnia, non-restorative sleep, excessive daytime somnolence, sleep apnea, and restlessness) in the Centre for Sleep and Chronobiology's Sleep Assessment Questionnaire^© (SAQ^©) were dichotomized based on threshold. The Epworth Sleepiness Scale score was used as a continuous variable.

Results

81.4% of subjects had an abnormality in at least one SAQ^© sleep factor. Subjects with sleep factor abnormalities had significantly lower wellness scores but statistically unchanged fatigue severity scores compared to those without SAQ^© abnormality. CFS subjects had significantly increased risk of abnormal scores in the non-restorative (adjusted odds ratio [OR] = 28.1; 95% confidence interval [CI]= 7.4–107.0) and restlessness (OR = 16.0; 95% CI = 4.2–61.6) SAQ^© factors compared to non-fatigued, but not for factors of sleep apnea or excessive daytime somnolence. This is consistent with studies finding that, while fatigued, CFS subjects are not sleepy. A strong correlation (0.78) of Epworth score was found only for the excessive daytime somnolence factor.

Conclusions

SAQ^© factors describe sleep abnormalities associated with CFS and provide more information than the Epworth score. Validation of these promising results will require formal polysomnographic sleep studies.