Investigating femoral growth disruption in subadults from the 10th-13th century St. Étienne cemetery of Toulouse, France.

OBJECTIVES: The skeleton embodies an individual's environment and lived experiences. Studying childhood growth disruption can, therefore, aid in understanding the experiences of children in the past. This study evaluates growth disruption in a medieval Toulousian subadult sample to explore factors that may have influenced childhood growth and mortality at this site and to assess the utility of Harris line (HL) interpretations in bioarchaeology. MATERIALS AND METHODS: Femoral growth disruption was assessed in n = 71 subadults (0.125-12.42 years) from the 10th-13th century St. Étienne cemetery of Toulouse, France, using femoral length, total area, cortical area, and relative cortical area. Femoral radiographs were assessed for HLs. To determine the prevalence of growth disruption, z-scores were calculated using data from the Denver growth study. RESULTS: The majority of subadults in this sample suffered from femoral growth disruption. Young children (1.0-3.99 years) were the most affected, with >65% experiencing reduced appositional growth and linear growth stunting at time-of-death. Additionally, while many individuals presented with observable HLs, linear and appositional growth did not significantly differ between individuals with and without HLs. DISCUSSION: Maternal malnutrition and inadequate complementary feeding practices likely contributed to the high prevalence of growth disruption among the youngest individuals in the study. The older children and adolescents buried at St. Étienne experienced an amelioration in growth deficits, indicating an improvement in nutrition and/or disease load. The results of this study suggest that more consideration is required when interpreting the presence/absence of HLs, and that studies assessing HLs may benefit from using a more individualistic approach.

A systematic evaluation of normalization methods and probe replicability using infinium EPIC methylation data.

BACKGROUND: The Infinium EPIC array measures the methylation status of > 850,000 CpG sites. The EPIC BeadChip uses a two-array design: Infinium Type I and Type II probes. These probe types exhibit different technical characteristics which may confound analyses. Numerous normalization and pre-processing methods have been developed to reduce probe type bias as well as other issues such as background and dye bias. METHODS: This study evaluates the performance of various normalization methods using 16 replicated samples and three metrics: absolute beta-value difference, overlap of non-replicated CpGs between replicate pairs, and effect on beta-value distributions. Additionally, we carried out Pearson's correlation and intraclass correlation coefficient (ICC) analyses using both raw and SeSAMe 2 normalized data. RESULTS: The method we define as SeSAMe 2, which consists of the application of the regular SeSAMe pipeline with an additional round of QC, pOOBAH masking, was found to be the best performing normalization method, while quantile-based methods were found to be the worst performing methods. Whole-array Pearson's correlations were found to be high. However, in agreement with previous studies, a substantial proportion of the probes on the EPIC array showed poor reproducibility (ICC < 0.50). The majority of poor performing probes have beta values close to either 0 or 1, and relatively low standard deviations. These results suggest that probe reliability is largely the result of limited biological variation rather than technical measurement variation. Importantly, normalizing the data with SeSAMe 2 dramatically improved ICC estimates, with the proportion of probes with ICC values > 0.50 increasing from 45.18% (raw data) to 61.35% (SeSAMe 2).

An Investigation of Micro-CT Analysis of Bone as a New Diagnostic Method for Paleopathological Cases of Osteomalacia.

OBJECTIVE: This paper looks to broaden the methodological possibilities for diagnosing osteomalacia in archaeological bone using micro-CT analysis. Increasing the identification of osteomalacia in paleopathology will provide support for important interpretive frameworks. MATERIALS: Nine embedded and two unembedded rib fragments were sourced from St. Martin's Birmingham and Ancaster, UK, and Lisieux Michelet, France. Of the 11 samples, nine were previously confirmed as osteomalacic, and presented with varying levels of diagenesis and two were non-osteomalacic controls, one of which exhibits diagenetic change. METHODS: Micro-CT, backscattered scanning electron microscopy, and light microscopy were employed. Micro-CT images were evaluated for osteomalacic features using corresponding microscopic images. RESULTS: Micro-CT images from osteomalacic samples demonstrated the presence of defective mineralization adjacent to cement lines, areas of incomplete mineralization, and resorptive bays/borders, three key diagnostic features of osteomalacia. Diagenetic change was also detectable in micro-CT images, but did not prevent the diagnosis of osteomalacia. CONCLUSIONS: Micro-CT analysis is a non-destructive method capable of providing microstructural images of osteomalacic features in embedded and unembedded samples. When enough of these features are present, micro-CT images are capable of confirming a diagnosis of osteomalacia. SIGNIFICANCE: Vitamin D deficiency has important health consequences which operate throughout the life course. Increasing the ability to detect cases of vitamin D deficiency provides researchers with a greater understanding of health and disease in past communities. LIMITATIONS: Only adult rib samples were used. SUGGESTIONS FOR FURTHER RESEARCH: Paleopathologists should look to test the utility of micro-CT analysis in diagnosing active rickets in subadult individuals.

Correction to: Incidental diagnosis of tuberous sclerosis complex by exome sequencing in three families with subclinical findings.

The published online version contain mistake in the author list. Instead of "A.M.Ilyas" it should have been "M.Ilyas ".

Incidental diagnosis of tuberous sclerosis complex by exome sequencing in three families with subclinical findings.

Tuberous sclerosis complex (TSC) is an autosomal-dominant neurocutaneous disorder characterized by lesions and benign tumors in multiple organ systems including the brain, skin, heart, eyes, kidneys, and lungs. The phenotype is highly variable, although penetrance is reportedly complete. We report the molecular diagnosis of TSC in individuals exhibiting extreme intra-familial variability, including the incidental diagnosis of asymptomatic family members. Exome sequencing was performed in three families, with probands referred for epilepsy, autism, and absent speech (Family 1); epileptic spasms (Family 2); and connective tissue disorders (Family 3.) Pathogenic variants in TSC1 or TSC2 were identified in nine individuals, including relatives with limited or no medical concerns at the time of testing. Of the nine individuals reported here, six had post-diagnosis examinations and three met clinical diagnostic criteria for TSC. One did not meet clinical criteria for a possible or definite diagnosis of TSC, and two had only a possible clinical diagnosis following post-diagnosis workup. These individuals as well as their mothers demonstrated limited features that would not raise concern for TSC in the absence of molecular results. In addition, three individuals exhibited epilepsy with normal brain MRIs, and two without seizures or intellectual disability had MRI findings fulfilling major criteria for TSC highlighting the difficulty providers face when relying on clinical criteria to guide genetic testing. Given the importance of a timely TSC diagnosis for clinical management, such cases demonstrate a potential benefit for clinical criteria to include seizures and an unbiased molecular approach to genetic testing.

Abnormalities of cerebral lateralization in schizophrenia patients.

Initial lateral eye movements (LEMs) have been shown to be associated with activation of the contralateral frontal lobes. Using LEM as a criterion measure of activation, schizophrenics were compared to normals with respect to the processing of four types of stimuli: verbal nonemotional (VNE), verbal emotional (VE), spatial nonemotional (SNE), and spatial emotional (SE). Our results indicate that schizophrenics initiate thought in their left hemisphere significantly more often than controls when one compares all test conditions and on VNE, VE, and SE material. Neither medication nor level of education had an appreciable effect on LEM in either group. However, sex was a significant variable; women irrespective of diagnosis consistently used the left hemisphere more often than men. The inappropriate initiation of thought on SE material as well as the overall increase in left hemisphere activity suggest left hemisphere disorder. This is consistent with other findings that suggest a left hemisphere locus of disturbance in schizophrenia.

Hypersensitization by baking of certain Kodak photographic prates for use in high-resolution Raman spectroscopy.

Hypersensitization by baking of various Kodak photographic emulsions is studied from the point of view of high-resolution Raman spectroscopy. In the 4400-4900-A region baking can increase the sensitivity of IIa-O plates to ~4 times that of 103a-O plates for long exposures. In the Raman region for Ar(+) laser excitation, 4700-5800 A, baked Ila-D plates show good sensitivity and low reciprocity failure. Baked IIIa-J plates have better resolving power than the IIa-D type, but the reciprocity failure is greater, and the useful region does not extend beyond 5300 A.

Spectroscopy research at the McLennan physical laboratories of the University of Toronto.

Recent research of the Spectroscopy and Molecular Physics Research Group at the Department of Physics, University of Toronto, has been in the general areas: spectroscopy of compressed gases, low temperature spectroscopy, Raman spectra of low pressure gases, optical pumping, applications of lasers to light scattering, and interference spectroscopy in the laboratory and from high altitude balloons. Topics discussed in some detail in this communication are: bound states of hydrogen-foreign gas Van der Waals complexes, intensity anomalies in the Raman effect of solid hydrogen, pressure broadening in the Raman spectra of simple diatomic molecules, a synopsis of work on high resolution rotation and rotation-vibrational Raman spectra of gases, recent results on Brillouin scattering and Raman line widths using lasers, and collision broadening in the spectrum of zinc by optical pumping.