A novel approach to 3D modelling ground-penetrating radar (GPR) data - A case study of a cemetery and applications for criminal investigation.

Ground-penetrating radar (GPR) is an established geophysical technique used extensively for the accurate reconstruction of the shallow (<10 m) subsurface. Reconstructions have largely been completed and presented as 2D vertical and horizontal planes, leaving limited visualization of subsurface 3D shapes and their spatial relationships. With technological advancements, particularly the availability and integration of various software platforms, 3D modelling of GPR data is now emerging as the new standard. However, despite these developments, there remains an inadequate examination and testing of these techniques, particularly in determining if their application is beneficial and warranted. In this study we conducted a GPR grid survey on a churchyard cemetery to generate and evaluate 2D and 3D-modelled reconstructions of the cemetery burial sites. Data collection and processing was completed using a Sensors and Software Incorporated pulseEKKO™ Pro SmartCart GPR system and EKKO_Project™ software, respectively. The modelling component was achieved using Schlumberger's Petrel™ E & P software platform, which is tailored to the petroleum industry. The subsurface patterns present in the 2D and 3D models closely matched the cemetery plot plan, validating our data collection, processing, and modelling methods. Both models were adequate for 2D horizontal visualization of reflection patterns at any specific depth. The 3D model was used to identify the presence of a companion burial plot (stacked caskets) and possible leachate plumes below and encircling burial sites, both of which were not evident in the 2D model, highlighting the benefits of 3D modelling when discerning subsurface objects. We expect our findings to be of value to similar GPR studies, with particular significance to geoforensic studies and criminal investigations.

Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer.

Mosaicism, the presence of subpopulations of cells bearing somatic mutations, is associated with disease and aging and has been detected in diverse tissues, including apparently normal cells adjacent to tumors. To analyze mosaicism on a large scale, we surveyed haplotype-specific somatic copy number alterations (sCNAs) in 1,708 normal-appearing adjacent-to-tumor (NAT) tissue samples from 27 cancer sites and in 7,149 blood samples from The Cancer Genome Atlas. We find substantial variation across tissues in the rate, burden and types of sCNAs, including those spanning entire chromosome arms. We document matching sCNAs in the NAT tissue and the adjacent tumor, suggesting a shared clonal origin, as well as instances in which both NAT tissue and tumor tissue harbor a gain of the same oncogene arising in parallel from distinct parental haplotypes. These results shed light on pan-tissue mutations characteristic of field cancerization, the presence of oncogenic processes adjacent to cancer cells.

Ultrasound and histological measurements of dividing membrane thickness in twin gestations.

OBJECTIVE: To determine how prenatal ultrasound measurements of dividing membrane thickness correlate with postnatal histological measurements and chorionicity in twin gestations. METHODS: This was a prospective, longitudinal cohort study of twin gestations. Dividing membrane thickness was measured by transabdominal ultrasound, with the insonation beam both parallel and perpendicular to the membrane, in the second or third trimester, depending on when care was established. Ultrasound examinations were performed every 4 weeks following initial assessment until delivery. Measurements of membrane thickness from the first ultrasound examination were compared with histological measurements after delivery. RESULTS: A total of 45 twin pregnancies (32 dichorionic, 13 monochorionic) were included. Mean gestational age at initial ultrasound examination was 24.1 ± 7.3 weeks. Parallel ultrasound measurements of membrane thickness were 1.6 ± 0.8 mm for monochorionic and 2.5 ± 0.9 mm for dichorionic gestations (P = 0.001). Perpendicular ultrasound measurements were 1.6 ± 0.3 mm for monochorionic and 2.2 ± 0.8 mm for dichorionic gestations (P = 0.009). Inter- and intraobserver reliability of ultrasound measurements were 0.847 and 0.950, respectively. Parallel and perpendicular ultrasound measurements correlated better with each other (R = 0.807, P < 0.001) than with histological measurements of membrane thickness (Rparallel = 0.538, P < 0.001; Rperpendicular = 0.529, P < 0.001). Receiver-operating characteristics curve analyses to predict histological membrane thickness > 50th percentile resulted in an area under the curve (AUC) of 0.828 for parallel (P < 0.001) and 0.874 for perpendicular (P < 0.001) measurements with a cut-off value of 1.9 mm for both approaches. The AUCs for parallel and perpendicular measurements to predict dichorionicity were 0.892 (P < 0.001) and 0.823 (P < 0.001) with cut-off values of 1.9 and 1.8 mm, respectively. CONCLUSION: Prenatal ultrasound measurement of twin dividing membrane thickness is positively correlated with postnatal histological measurement. Dichorionicity can be determined by a magnified dividing membrane thickness ≥ 1.9 mm. Measurements with the ultrasound beam parallel to the dividing membrane may be more accurate than perpendicular measurements. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Adaptive genetic changes related to haemoglobin concentration in native high-altitude Tibetans.

NEW FINDINGS: What is the topic of this review? Tibetans have genetic adaptations that are hypothesized to underlie the distinct set of traits they exhibit at altitude. What advances does it highlight? Several adaptive signatures in the same genomic regions have been identified among Tibetan populations resident throughout the Qinghai-Tibetan Plateau. Many highland Tibetans exhibit a haemoglobin concentration within the range expected at sea level, and this trait is associated with putatively adaptive regions harbouring the hypoxia-inducible factor pathway genes EGLN1, EPAS1 and PPARA. Precise functional variants at adaptive loci and relationships to physiological traits, beyond haemoglobin concentration, are currently being examined in this population. Some native Tibetan, Andean and Ethiopian populations have lived at altitudes ranging from 3000 to >4000 m above sea level for hundreds of generations and exhibit distinct combinations of traits at altitude. It was long hypothesized that genetic factors contribute to adaptive differences in these populations, and recent advances in genomics provide evidence that some of the strongest signatures of positive selection in humans are those identified in Tibetans. Many of the top adaptive genomic regions highlighted thus far harbour genes related to hypoxia sensing and response. Putatively adaptive copies of three hypoxia-inducible factor pathway genes, EPAS1, EGLN1 and PPARA, are associated with sea-level range, rather than elevated, haemoglobin concentration observed in many Tibetans at high altitude, and recent studies provide insight into some of the precise adaptive variants, timing of adaptive events and functional roles. While several studies in highland Tibetans have converged on a few hypoxia-inducible factor pathway genes, additional candidates have been reported in independent studies of Tibetans located throughout the Qinghai-Tibetan Plateau. Various aspects of adaptive significance have yet to be identified, integrated, and fully explored. Given the rapid technological advances and interdisciplinary efforts in genomics, physiology and molecular biology, careful examination of Tibetans and comparisons with other distinctively adapted highland populations will provide valuable insight into evolutionary processes and models for both basic and clinical research.

Genetic risk factors in two Utah pedigrees at high risk for suicide.

We have used unique population-based data resources to identify 22 high-risk extended pedigrees that show clustering of suicide over twice that expected from demographically adjusted incidence rates. In this initial study of genetic risk factors, we focused on two high-risk pedigrees. In the first of these (pedigree 12), 10/19 (53%) of the related suicides were female, and the average age at death was 30.95. In the second (pedigree 5), 7/51 (14%) of the suicides were female and the average age at death was 36.90. Six decedents in pedigree 12 and nine in pedigree 5 were genotyped with the Illumina HumanExome BeadChip. Genotypes were analyzed using the Variant Annotation, Analysis, and Search program package that computes likelihoods of risk variants using the functional impact of the DNA variation, aggregative scoring of multiple variants across each gene and pedigree structure. We prioritized variants that were: (1) shared across pedigree members, (2) rare in other Utah suicides not related to these pedigrees, (3) < or = 5% in genotyping data from 398 other Utah population controls and (4) < or = 5% frequency in publicly available sequence data from 1358 controls and/or in dbSNP. Results included several membrane protein genes (ANO5, and TMEM141 for pedigree 12 and FAM38A and HRCT1 for pedigree 5). Other genes with known neuronal involvement and/or previous associations with psychiatric conditions were also identified, including NFKB1, CASP9, PLXNB1 and PDE11A in pedigree 12, and THOC1, and AUTS2 in pedigree 5. Although the study is limited to variants included on the HumanExome BeadChip, these findings warrant further exploration, and demonstrate the utility of this high-risk pedigree resource to identify potential genes or gene pathways for future development of targeted interventions.

Salvage transplantation for allograft failure using fludarabine and alemtuzumab as conditioning regimen.

Graft failure after allogeneic blood or marrow transplantation, although generally uncommon, can be a devastating complication. This report includes the outcome of nine patients who received a salvage transplant for failure to engraft after one (n=8) or 2 (n=1) prior transplants. Eight patients received allografts from the original donor. All received fludarabine 30 mg/m(2) i.v. and alemtuzumab 20 mg i.v. daily from days -6 to -2. Daily CYA was begun on day -2, and the allograft was infused on day 0. The therapy was well tolerated with low toxicity, and all nine patients engrafted, recovering neutrophils at a median of 12 days after transplant. Four patients died: two of relapse, one of a fungal infection in the setting of GVHD and one of multiple sclerosis. The combination of fludarabine and alemtuzumab is an effective and well-tolerated salvage conditioning regimen for patients who experience graft failure after blood or marrow transplants.

Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases.

Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorting of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. We now describe a novel member of this family, SNX6, which interacts with members of the transforming growth factor-beta family of receptor serine-threonine kinases. These receptors belong to two classes: type II receptors that bind ligand, and type I receptors that are subsequently recruited to transduce the signal. Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of TbetaRII. Of the type I receptors, SNX6 was found to interact only with inactivated TbetaRI. SNXs 1-4 also interacted with the transforming growth factor-beta receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. These findings are the first evidence for the association of the SNX family of molecules with receptor serine-threonine kinases.

A novel smad nuclear interacting protein, SNIP1, suppresses p300-dependent TGF-beta signal transduction.

Members of the transforming growth factor-beta superfamily play critical roles in controlling cell growth and differentiation. Effects of TGF-beta family ligands are mediated by Smad proteins. To understand the mechanism of Smad function, we sought to identify novel interactors of Smads by use of a yeast two-hybrid system. A 396-amino acid nuclear protein termed SNIP1 was cloned and shown to harbor a nuclear localization signal (NLS) and a Forkhead-associated (FHA) domain. The carboxyl terminus of SNIP1 interacts with Smad1 and Smad2 in yeast two-hybrid as well as in mammalian overexpression systems. However, the amino terminus of SNIP1 harbors binding sites for both Smad4 and the coactivator CBP/p300. Interaction between endogenous levels of SNIP1 and Smad4 or CBP/p300 is detected in NMuMg cells as well as in vitro. Overexpression of full-length SNIP1 or its amino terminus is sufficient to inhibit multiple gene responses to TGF-beta and CBP/p300, as well as the formation of a Smad4/p300 complex. Studies in Xenopus laevis further suggest that SNIP1 plays a role in regulating dorsomedial mesoderm formation by the TGF-beta family member nodal. Thus, SNIP1 is a nuclear inhibitor of CBP/p300 and its level of expression in specific cell types has important physiological consequences by setting a threshold for TGF-beta-induced transcriptional activation involving CBP/p300.

Source, recency, and degree of stress in adolescence and suicide ideation.

This study sought to identify factors related to stress that predict suicide ideation among adolescents. The sample consisted of 425 students aged 14 to 18 years. Multiple regression analysis revealed that recency and degree of stress were significant in the prediction of degree and recency of suicide ideation. The implications of these and other findings for prevention and intervention (e.g., health education, parent workshops, and adolescent support groups) are discussed.

Back-to-school bonus. Kaiser picks up the premiums--and helps displaced homemakers earn college diplomas.

Kaiser Permanente Northwest gave the old college try to help women without health insurance. Under a program for Oregon homemakers displaced by divorce or a spouse's death, Kaiser pays their insurance premiums so they can stay in school, earn their degrees, and boost their job prospects.

Hospital heavies. Venture capital bulks up companies that outsource medicine's newest specialty: inpatient-only care.

They're the designated drivers of inpatient care, cutting hospital stays by 19 percent on average. Yet as venture capital firms infuse hospitalist startup companies, some primary care doctors complain that their sickest patients are being taken away from them.

Time course of hypo-osmotic swellings of human spermatozoa: evidence of ordered transition between swelling subtypes.

The hypo-osmotic swelling test (HOST or HOS test) usually takes into consideration the total HOS response value with no emphasis either on the value of the response subtypes or the response evaluation time. This study investigated the time course of HOS responses and analysed their physiological relevance. Raw semen spermatozoa and Percoll washed spermatozoa were used in the experiment. The morphological changes in the sperm tail were monitored by incubating the spermatozoa in the hypo-osmotic solution for 16 different time periods. The HOS reactive spermatozoa and the type of HOS reaction (swelling subtypes) of the samples subjected to different duration of treatment were identified under a phase contrast microscope. Also the fate of individual spermatozoa in a hypo-osmotic environment were monitored for 30 min. In spermatozoa exposed to a hypo-osmotic solution, the motility lasted usually less than 2 min and motility characteristics were uniquely different from that of the spermatozoa under iso-osmotic conditions. The HOS response development was permanent but the motility loss due to hypo-osmotic shock was reversible up to 1 min of incubation. There was an indication of ordered transition among the HOS swelling subtypes apparently initiating with subtype b destined to c, d, e, f and g. Further, the subtypes a and g showed gradual decrease and increase, respectively, while subtype b showed abrupt initial increase and then gradual decrease. Transition from b to g could be direct or via one or more than one subtypes. Ultrastructure based analysis indicated that HOS response subtypes are the apparent reflection of the differences in the cytoskeletal assembly of the sperm tail and thus may be identifying different physiological variants in the sperm population. These results indicate that shorter incubation is essential to document the kinetics of various HOS responses but the conventional HOS test misses these important HOS features because of lengthy incubation. Since the time course of ordered transition of HOS responses will vary more than the total HOS response in semen of different aetiologies, the importance of HOS response subtypes and response evaluation time should be taken into consideration when applying HOS test.

Facial port wine stains in childhood: prediction of the rate of improvement as a function of the age of the patient, size and location of the port wine stain and the number of treatments with the pulsed dye (585 nm) laser.

In this study we examined the rate of decrease in size of facial port wine stains (PWS) as a function of number of treatments, lesion size, lesion location and patients' age. This study was performed at the University of Colorado Hospital Outpatient Dermatology Center, Denver, U.S.A. A consecutive sample of 91 patients 18 years of age or younger with facial PWS in which the entire lesion was treated at each visit were studied. Included were all patients who had a minimum of five treatments or complete clearance of their lesion in fewer than five treatments. Patients were evaluated following one, five and 10 treatments with the pulsed (450 s) dye (585 nm) laser. Improvement was defined as the percentage decrease in the size of the PWS. For all patients, the first five treatments resulted in a mean decrease in size of 55% while the second five treatments (38 patients) only improved the mean decrease in size by 18%. Grouped by location, the mean decreases in size from the first five and the second five treatments were as follows: central forehead = 100%, 0%; peripheral face = 58%, 28%; central face = 48%, 14%; and mixed (combination of peripheral and central face) = 21%, 9%. All central forehead PWS completely cleared within five treatments while none of the mixed PWS did so even with an average of 14 treatments. Grouped by size, mean decrease in size was highest for small lesions; < 20 cm2 = 67%, 21%; 20 to < 40 cm2 = 45%, 8%; and > 40 cm2 = 23%, 29%. Grouped by age, mean decrease in size was highest for young children: < 1-year-old = 63%, 33%; 1 to < 6 years = 48%, 15%; and older than 6 years = 54%, 10%. For all patients studied, maximal improvement was obtained in the first five treatments. Major determinants of treatment response in order of decreasing importance are PWS location, size and patients' age. The most successful responses are seen in young patients (less than 1 year old) with small PWS (under 20 cm2) that are located over bony areas of the face such as the central forehead. These three determinants may be useful tools to guide patient expectations and to predict the rate of improvement of PWS to pulsed dye laser treatment.

Home-grown health plan.

Most companies in Sullivan County, N.H., employ fewer than five people, so a decade of economic decline meant many could't afford to offer health benefits. Valley Regional Healthcare saw its chance to help out the community, launching an HMO-style plan that keeps control--and spending--local.