A surface-fitting program for areally- distributed data from the earth sciences and remote sensing

Fortran II program for analysis of data from earth sciences and remote sensin

Rapid generation of chromosome-specific alphoid DNA probes using the polymerase chain reaction

Non-isotopic in situ hybridization of chromosome-specific alphoid DNA probes has become a potent tool in the study of numerical aberrations of specific human chromosomes at all stages of the cell cycle. In this paper, we describe approaches for the rapid generation of such probes using the polymerase chain reaction (PCR), and demonstrate their chromosome specificity by fluorescence in situ hybridization to normal human metaphase spreads and interphase nuclei. Oligonucleotide primers for conserved regions of the alpha satellite monomer were used to generate chromosome-specific DNA probes from somatic hybrid cells containing various human chromosomes, and from DNA libraries from sorted human chromosomes. Oligonucleotide primers for chromosome-specific regions of the alpha satellite monomer were used to generate specific DNA probes for the pericentromeric heterochromatin of human chromosomes 1, 6, 7, 17 and X directly from human genomic DNA

Gene expression dynamics underlying cell fate emergence in 2D micropatterned human embryonic stem cell gastruloids

Human embryonic stem cells cultured in 2D micropatterns with BMP4 differentiate into a radial arrangement of germ layers and extraembryonic cells. Single-cell transcriptomes demonstrate generation of cell types transcriptionally similar to their in vivo counterparts in Carnegie stage 7 human gastrula. Time-course analyses indicate sequential differentiation, where the epiblast arises by 12 h between the prospective ectoderm in the center and the cells initiating differentiation toward extraembryonic fates at the edge. Extraembryonic and mesendoderm precursors arise from the epiblast by 24 h, while nascent mesoderm, endoderm, and primordial germ cell-like cells form by 44 h. Dynamic changes in transcripts encoding signaling components support a BMP, WNT, and Nodal hierarchy underlying germ-layer specification conserved across mammals, and FGF and HIPPO pathways being active throughout differentiation. This work also provides a resource for mining genes and pathways expressed in a stereotyped 2D gastruloid model, common with other species or unique to human gastrulation

Examining the clinical use of hemochromatosis genetic testing

BACKGROUND: Hereditary hemochromatosis leads to an increased lifetime risk for end-organ damage due to excess iron deposition. Guidelines recommend that genetic testing be performed in patients with clinical suspicion of iron overload accompanied by elevated serum ferritin and transferrin saturation levels. OBJECTIVE: To evaluate guideline adherence and the clinical and economic impact of HFE genetic testing. METHODS: The electronic charts of patients submitted for HFE testing in 2012 were reviewed for genetic testing results, biochemical markers of iron overload and clinical history of phlebotomy. RESULTS: A total of 664 samples were sent for testing, with clinical, biochemical and phlebotomy data available for 160 patients. A positive C282Y homozygote or C282Y/H63D compound heterozygote test result was observed in 18% of patients. Patients with an at-risk HFE genotype had significantly higher iron saturation, serum iron and hemoglobin (P\u3c0.001), without higher ferritin or liver enzyme levels. Fifty percent of patients referred for testing did not have biochemical evidence of iron overload (transferrin saturation \u3e45% and ferritin level \u3e300μg/L). Patients were four times more likely to undergo phlebotomy if they were gene test positive (RR 4.29 [95% CI 2.35 to 7.83]; P\u3c0.00001). DISCUSSION: One-half of patients referred for testing did not exhibit biochemical evidence of iron overload. Many patients with biochemical evidence of iron overload, but with negative genetic test results, did not undergo phlebotomy. A requisition to determine clinical indication for testing may reduce the use of the HFE genetic test. Finally, improvement of current genetic test characteristics would improve rationale for the test. CONCLUSION: A significant proportion of hemochromatosis genetic testing does not adhere to current guidelines and would not alter patient management

Jejunal Perforation following Screening Colonoscopy

Colonoscopy is rarely associated with complications such as colonic perforation. Perforation of the small bowel is extremely rare, especially if the procedure is done without therapeutic interventions. Several factors are associated with this entity. Perforation of the ileum has been reported, but proximal jejunal perforation secondary to rupture of jejunal diverticulum during colonoscopy has not been reported. We present the case of an 88-year-old patient who developed abdominal pain after undergoing colonoscopy without any additional interventions. Urgent exploration revealed perforation of the proximal jejunum secondary to rupture of a jejunal diverticulum. No therapy or biopsies were undertaken during the colonoscopy, which are known predisposing factors

Assessing the exposure-response relationship of sleep disturbance and vibration in field and laboratory settings

Exposure to nocturnal freight train vibrations may impact sleep, but exposure-response relationships are lacking. The European project CargoVibes evaluated sleep disturbance both in the field and in the laboratory and provides unique data, as measures of response and exposure metrics are comparable. This paper therefore provides data on exposure-response relationships of vibration and sleep disturbance and compares the relationships evaluated in the laboratory and the field. Two field studies (one in Poland and one in the Netherlands) with 233 valid respondents in total, and three laboratory studies in Sweden with a total of 59 subjects over 350 person-nights were performed. The odds ratios (OR) of sleep disturbance were analyzed in relation to nighttime vibration exposure by ordinal logit regression, adjusting for moderating factors common for the studies. Outcome specific fractions were calculated for eleven sleep outcomes and supported comparability between the field and laboratory settings. Vibration exposure was significantly associated to sleep disturbance, OR = 3.51 (95% confidence interval 2.6–4.73) denoting a three and a half times increased odds of sleep disturbance with one unit increased 8 h nighttime log10 Root Mean Square vibration. The results suggest no significant difference between field and laboratory settings OR = 1.37 (0.59–3.19). However, odds of sleep disturbance were higher in the Netherlands as compared to Sweden, indicating unexplained differences between study populations or countries, possibly related to cultural and contextual differences and uncertainties in exposure assessments. Future studies should be carefully designed to record explanatory factors in the field and enhance ecological validity in the laboratory. Nevertheless, the presented combined data set provides a first set of exposure response relationships for vibration-induced sleep disturbance, which are useful when considering public health outcomes among exposed populations

Neuroendocrine Disruption: More than Hormones are Upset

Only a small proportion of the published research on endocrine-disrupting chemicals (EDC) directly examined effects on neuroendocrine processes. There is an expanding body of evidence that anthropogenic chemicals exert effects on neuroendocrine systems and that these changes might impact peripheral organ systems and physiological processes. Neuroendocrine disruption extends the concept of endocrine disruption to include the full breadth of integrative physiology (i.e., more than hormones are upset). Pollutants may also disrupt numerous other neurochemical pathways to affect an animal's capacity to reproduce, develop and grow, or deal with stress and other challenges. Several examples are presented in this review, from both vertebrates and invertebrates, illustrating that diverse environmental pollutants including pharmaceuticals, organochlorine pesticides, and industrial contaminants have the potential to disrupt neuroendocrine control mechanisms. While most investigations on EDC are carried out with vertebrate models, an attempt is also made to highlight the importance of research on invertebrate neuroendocrine disruption. The neurophysiology of many invertebrates is well described and many of their neurotransmitters are similar or identical to those in vertebrates; therefore, lessons learned from one group of organisms may help us understand potential adverse effects in others. This review argues for the adoption of systems biology and integrative physiology to address the effects of EDC. Effects of pulp and paper mill effluents on fish reproduction are a good example of where relatively narrow hypothesis testing strategies (e.g., whether or not pollutants are sex steroid mimics) have only partially solved a major problem in environmental biology. It is clear that a global, integrative physiological approach, including improved understanding of neuroendocrine control mechanisms, is warranted to fully understand the impacts of pulp and paper mill effluents. Neuroendocrine disruptors are defined as pollutants in the environment that are capable of acting as agonists/antagonists or modulators of the synthesis and/or metabolism of neuropeptides, neurotransmitters, or neurohormones, which subsequently alter diverse physiological, behavioral, or hormonal processes to affect an animal's capacity to reproduce, develop and grow, or deal with stress and other challenges. By adopting a definition of neuroendocrine disruption that encompasses both direct physiological targets and their indirect downstream effects, from the level of the individual to the ecosystem, a more comprehensive picture of the consequences of environmentally relevant EDC exposure may emerge

Detecting colorectal cancer using electrical impedance spectroscopy: an ex vivo feasibility study

Objective: Colorectal cancer is the fourth most common cancer worldwide, with a lifetime risk of around 20%. Current solutions do not allow clinicians to objectively assess tissue abnormality during endoscopy and perioperatively. A solution capable of objectively assessing samples in real time could greatly improve the treatment process. A solution that can be integrated in minimally invasive diagnostics and management strategies to provide real-time point-of-care information would be greatly transformative. Electrical impedance spectroscopy (EIS) may provide such a solution. In this paper, we present a feasibility study on using EIS in assessing colorectal tissue. Approach: We performed tetrapolar EIS using ZedScan on excised human colorectal tumour tissue and the matched normal colonic mucosa in 22 freshly resected specimens following elective surgery for colorectal cancer. Histopathological examination was used to confirm the final diagnosis. Statistical significance was assessed with Wilcoxon signed rank test. Main results: Tetrapolar EIS could discriminate cancer with statistically significant results when applying frequencies between 305 Hz – 625 kHz (p < 0.05). 300 Ω was set as the transfer impedance threshold to detect cancer. Thus, the area under the corresponding receiver operating characteristic curve for this threshold was 0.7105. Significance: This feasibility study demonstrates that impedance spectra changes in colorectal cancer tissue are detectable and may be statistically significant, suggesting that EIS has the potential to be the core technology in a novel non-invasive point of care test for detecting colorectal cancer. These results warrant further development and increasing the size of the study with a device specificity designed for colorectal cancer

Single-cell analysis reveals regional reprogramming during adaptation to massive small bowel resection in mice

BACKGROUND & AIMS: The small intestine (SI) displays regionality in nutrient and immunological function. Following SI tissue loss (as occurs in short gut syndrome, or SGS), remaining SI must compensate, or adapt ; the capacity of SI epithelium to reprogram its regional identity has not been described. Here, we apply single-cell resolution analyses to characterize molecular changes underpinning adaptation to SGS. METHODS: Single-cell RNA sequencing was performed on epithelial cells isolated from distal SI of mice following 50% proximal small bowel resection (SBR) vs sham surgery. Single-cell profiles were clustered based on transcriptional similarity, reconstructing differentiation events from intestinal stem cells (ISCs) through to mature enterocytes. An unsupervised computational approach to score cell identity was used to quantify changes in regional (proximal vs distal) SI identity, validated using immunofluorescence, immunohistochemistry, qPCR, western blotting, and RNA-FISH. RESULTS: Uniform Manifold Approximation and Projection-based clustering and visualization revealed differentiation trajectories from ISCs to mature enterocytes in sham and SBR. Cell identity scoring demonstrated segregation of enterocytes by regional SI identity: SBR enterocytes assumed more mature proximal identities. This was associated with significant upregulation of lipid metabolism and oxidative stress gene expression, which was validated via orthogonal analyses. Observed upstream transcriptional changes suggest retinoid metabolism and proximal transcription factor Creb3l3 drive proximalization of cell identity in response to SBR. CONCLUSIONS: Adaptation to proximal SBR involves regional reprogramming of ileal enterocytes toward a proximal identity. Interventions bolstering the endogenous reprogramming capacity of SI enterocytes-conceivably by engaging the retinoid metabolism pathway-merit further investigation, as they may increase enteral feeding tolerance, and obviate intestinal failure, in SGS

Violence at University Pilot Project: Student experiences of violence, harassment and discrimination

The aim of this pilot study was to investigate the feasibility of measuring violence, in all of its forms, both within and beyond University Campuses. The study wanted to examine students’ experiences of violence during their time as university students’. It was not a prevalence study, rather it was to assess whether such a tool could be developed, and potential prevalence work could be conducted. The core goals were to assess if: a)It is feasible to do this work. b)It helps to continue the sector wide Universities UK Changing the Culture Initiative andsupport the development of strategies at institutional level. c)It identifies any gaps with regard to tackling violence on campus. The findings in this report are based on data gathered using the Violence at University Questionnaire. The full survey is available in the accompanying Appendix and the research team would welcome its use and any feedback from fellow HEI’s. This project was funded by the R&E QR Strategic Priorities Fund (QR-SPF) and we are extremely grateful for the opportunity to carry out this vital research